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Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein.
Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Sattler R, et al. Among authors: tymianski m. Science. 1999 Jun 11;284(5421):1845-8. doi: 10.1126/science.284.5421.1845. Science. 1999. PMID: 10364559
In cultured cortical neurons, suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density-95) selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca2+) channels. ...Thus, PSD-9 …
In cultured cortical neurons, suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density-95) sel …
Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions.
Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, Wang YT, Salter MW, Tymianski M. Aarts M, et al. Among authors: tymianski m. Science. 2002 Oct 25;298(5594):846-50. doi: 10.1126/science.1072873. Science. 2002. PMID: 12399596
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein …
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke …
Peptide action in stroke therapy.
Aarts MM, Tymianski M. Aarts MM, et al. Among authors: tymianski m. Expert Opin Biol Ther. 2003 Oct;3(7):1093-104. doi: 10.1517/14712598.3.7.1093. Expert Opin Biol Ther. 2003. PMID: 14519074 Review.
This has contributed to the failure of clinical trials employing glutamate receptor antagonists as stroke therapeutics. However, recent years have seen an increased understanding of the molecular organisation of glutamate receptors in the neuronal postsynaptic density. ... …
This has contributed to the failure of clinical trials employing glutamate receptor antagonists as stroke therapeutics. However, rece …
Novel concepts in excitotoxic neurodegeneration after stroke.
Aarts MM, Arundine M, Tymianski M. Aarts MM, et al. Among authors: tymianski m. Expert Rev Mol Med. 2003 Dec 16;5(30):1-22. doi: 10.1017/S1462399403007087. Expert Rev Mol Med. 2003. PMID: 14987406 Review.
Brain injury following cerebral ischaemia (stroke) involves a complex combination of pathological processes, including excitotoxicity and inflammation leading to necrotic and apoptotic forms of cell death. ...These findings have important implications in the search for eff …
Brain injury following cerebral ischaemia (stroke) involves a complex combination of pathological processes, including excitotoxicity …
Molecular mechanisms underlying specificity of excitotoxic signaling in neurons.
Aarts MM, Tymianski M. Aarts MM, et al. Among authors: tymianski m. Curr Mol Med. 2004 Mar;4(2):137-47. doi: 10.2174/1566524043479202. Curr Mol Med. 2004. PMID: 15032710 Review.
The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic iono …
The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well establis …
Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury.
Arundine M, Tymianski M. Arundine M, et al. Among authors: tymianski m. Cell Mol Life Sci. 2004 Mar;61(6):657-68. doi: 10.1007/s00018-003-3319-x. Cell Mol Life Sci. 2004. PMID: 15052409 Free PMC article. Review.
Stroke and neurotrauma mediate neuronal death through a series of events that involve multiple interdependent molecular pathways. ...We also highlight a novel, peptide-based approach for uncoupling NMDA receptors from excitotoxicity in the rat central nervous system subjec …
Stroke and neurotrauma mediate neuronal death through a series of events that involve multiple interdependent molecular pathways. ... …
TRPM7 and ischemic CNS injury.
Aarts MM, Tymianski M. Aarts MM, et al. Among authors: tymianski m. Neuroscientist. 2005 Apr;11(2):116-23. doi: 10.1177/1073858404272966. Neuroscientist. 2005. PMID: 15746380 Review.
To date, few effective therapies have been realized to treat stroke and once promising avenues such as antiexcitotoxic therapy with NMDA receptor antagonists have not proven clinically useful. Thus, we need to identify new targets for research and therapeutic intervention …
To date, few effective therapies have been realized to treat stroke and once promising avenues such as antiexcitotoxic therapy with N …
Inhibition of caspase-mediated apoptosis by peroxynitrite in traumatic brain injury.
Lau A, Arundine M, Sun HS, Jones M, Tymianski M. Lau A, et al. Among authors: tymianski m. J Neurosci. 2006 Nov 8;26(45):11540-53. doi: 10.1523/JNEUROSCI.3507-06.2006. J Neurosci. 2006. PMID: 17093075 Free PMC article.
In traumatic brain injury (TBI), neurons surviving the primary insult may succumb through poorly understood secondary mechanisms. ...Our data show that caspase-mediated apoptosis is inhibited in neurons subjected to stretch in vitro and to TBI in vivo, mostly becaus …
In traumatic brain injury (TBI), neurons surviving the primary insult may succumb through poorly understood secondary mechanisms. ... …
NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo.
Liu Y, Wong TP, Aarts M, Rooyakkers A, Liu L, Lai TW, Wu DC, Lu J, Tymianski M, Craig AM, Wang YT. Liu Y, et al. Among authors: tymianski m. J Neurosci. 2007 Mar 14;27(11):2846-57. doi: 10.1523/JNEUROSCI.0116-07.2007. J Neurosci. 2007. PMID: 17360906 Free PMC article.
Well-documented experimental evidence from both in vitro and in vivo models of stroke strongly supports the critical involvement of NMDA receptor-mediated excitotoxicity in neuronal damage after stroke. ...A similar opposing action of NR2B and NR2A in mediating cell …
Well-documented experimental evidence from both in vitro and in vivo models of stroke strongly supports the critical involvement of N …
PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors.
Cui H, Hayashi A, Sun HS, Belmares MP, Cobey C, Phan T, Schweizer J, Salter MW, Wang YT, Tasker RA, Garman D, Rabinowitz J, Lu PS, Tymianski M. Cui H, et al. Among authors: tymianski m. J Neurosci. 2007 Sep 12;27(37):9901-15. doi: 10.1523/JNEUROSCI.1464-07.2007. J Neurosci. 2007. PMID: 17855605 Free PMC article.
NR2A-NR2D subunits and Tat-NR2B9c had similar, highly specific, PDZ protein interactions, of which the strongest were with the PSD-95 family members (PSD-95, PSD-93, SAP97, and SAP102) and Tax interaction protein 1 (TIP1). ...IC50 values …
NR2A-NR2D subunits and Tat-NR2B9c had similar, highly specific, PDZ protein interactions, of which the strongest were with the …
Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke.
Besancon E, Guo S, Lok J, Tymianski M, Lo EH. Besancon E, et al. Among authors: tymianski m. Trends Pharmacol Sci. 2008 May;29(5):268-75. doi: 10.1016/j.tips.2008.02.003. Epub 2008 Apr 1. Trends Pharmacol Sci. 2008. PMID: 18384889 Review.
However, numerous clinical trials of glutamate receptor antagonists for the treatment of stroke were unsuccessful. These failures have led to pessimism in the field. But recent advances could provide hope for the future. ...Further in vivo validation of these pathways coul …
However, numerous clinical trials of glutamate receptor antagonists for the treatment of stroke were unsuccessful. These failures hav …
Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat.
Sun HS, Doucette TA, Liu Y, Fang Y, Teves L, Aarts M, Ryan CL, Bernard PB, Lau A, Forder JP, Salter MW, Wang YT, Tasker RA, Tymianski M. Sun HS, et al. Among authors: tymianski m. Stroke. 2008 Sep;39(9):2544-53. doi: 10.1161/STROKEAHA.107.506048. Epub 2008 Jul 10. Stroke. 2008. PMID: 18617669
Animals were treated with a single intravenous injection of postsynaptic density-95 inhibitors (Tat-NR2B9c([SDV]) or Tat-NR2B9c([TDV])) 1 hour or 3 hours after stroke. Infarct volumes and neurobehavior were assessed in a blinded manner at 24 hou …
Animals were treated with a single intravenous injection of postsynaptic density-95 inhibitors (Tat-NR2B9c([SDV]) or Tat …
Specific targeting of pro-death NMDA receptor signals with differing reliance on the NR2B PDZ ligand.
Soriano FX, Martel MA, Papadia S, Vaslin A, Baxter P, Rickman C, Forder J, Tymianski M, Duncan R, Aarts M, Clarke P, Wyllie DJ, Hardingham GE. Soriano FX, et al. Among authors: tymianski m. J Neurosci. 2008 Oct 15;28(42):10696-710. doi: 10.1523/JNEUROSCI.1207-08.2008. J Neurosci. 2008. PMID: 18923045 Free PMC article.
NMDAR-dependent p38 activation in neurons is triggered by submembranous Ca(2+), and is disrupted by NOS inhibitors and also a peptide mimicking the NR2B PDZ ligand (TAT-NR2B9c). TAT-NR2B9c reduced excitotoxic neuronal death and p38-mediated ischemic da …
NMDAR-dependent p38 activation in neurons is triggered by submembranous Ca(2+), and is disrupted by NOS inhibitors and also a peptide mimick …
Impaired cerebrovascular reactivity with steal phenomenon is associated with increased diffusion in white matter of patients with Moyamoya disease.
Conklin J, Fierstra J, Crawley AP, Han JS, Poublanc J, Mandell DM, Silver FL, Tymianski M, Fisher JA, Mikulis DJ. Conklin J, et al. Among authors: tymianski m. Stroke. 2010 Aug;41(8):1610-6. doi: 10.1161/STROKEAHA.110.579540. Epub 2010 Jun 24. Stroke. 2010. PMID: 20576954
BACKGROUND AND PURPOSE: Reduced cerebrovascular reactivity (CVR) with steal phenomenon is an independent predictor for stroke and may indicate tissue exposed to episodic low-grade ischemia. The apparent diffusion coefficient (ADC) calculated using diffusion-weighted MRI is …
BACKGROUND AND PURPOSE: Reduced cerebrovascular reactivity (CVR) with steal phenomenon is an independent predictor for stroke and may …
Can molecular and cellular neuroprotection be translated into therapies for patients?: yes, but not the way we tried it before.
Tymianski M. Tymianski M. Stroke. 2010 Oct;41(10 Suppl):S87-90. doi: 10.1161/STROKEAHA.110.595496. Stroke. 2010. PMID: 20876514 Review.
RESULTS: Although there is no evidence for fundamental barriers in biological principles that limit the translation of promising therapies to humans, ample evidence exists as to a lack of rigor in preclinical studies, obstacles posed by the complexities of acute ischemic strok …
RESULTS: Although there is no evidence for fundamental barriers in biological principles that limit the translation of promising therapies t …
Translating promising preclinical neuroprotective therapies to human stroke trials.
Cook DJ, Tymianski M. Cook DJ, et al. Among authors: tymianski m. Expert Rev Cardiovasc Ther. 2011 Apr;9(4):433-49. doi: 10.1586/erc.11.34. Expert Rev Cardiovasc Ther. 2011. PMID: 21517728 Review.
Stroke is the third leading cause of mortality and carries the greatest socioeconomic burden of disease in North America. ...To improve the chance of success in future human stroke trials, we propose that therapies be tested in stroke models that closely rese …
Stroke is the third leading cause of mortality and carries the greatest socioeconomic burden of disease in North America. ...To impro …
Impact of extracranial-intracranial bypass on cerebrovascular reactivity and clinical outcome in patients with symptomatic moyamoya vasculopathy.
Han JS, Abou-Hamden A, Mandell DM, Poublanc J, Crawley AP, Fisher JA, Mikulis DJ, Tymianski M. Han JS, et al. Among authors: tymianski m. Stroke. 2011 Nov;42(11):3047-54. doi: 10.1161/STROKEAHA.111.615955. Epub 2011 Sep 8. Stroke. 2011. PMID: 21903951
One patient had a clinical perioperative stroke (1.8%). In clinical follow-up, 37 of 39 patients (95%) had stable or improved modified Rankin Scale scores and 2 patients (5.1%) worsened. ...
One patient had a clinical perioperative stroke (1.8%). In clinical follow-up, 37 of 39 patients (95%) had stable or improved modifie …
Neuroprotection by freezing ischemic penumbra evolution without cerebral blood flow augmentation with a postsynaptic density-95 protein inhibitor.
Bråtane BT, Cui H, Cook DJ, Bouley J, Tymianski M, Fisher M. Bråtane BT, et al. Among authors: tymianski m. Stroke. 2011 Nov;42(11):3265-70. doi: 10.1161/STROKEAHA.111.618801. Epub 2011 Sep 8. Stroke. 2011. PMID: 21903963
RESULTS: Final infarct volume was decreased by 30.3% in the Tat-NR2B9c-treated animals compared with controls (P=0.028). There was a significant improvement in 24 hours neurological scores in the Tat-NR2B9c group compared with controls, 1.80.5 and 2.81 …
RESULTS: Final infarct volume was decreased by 30.3% in the Tat-NR2B9c-treated animals compared with controls (P=0.028). There …
Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain.
Cook DJ, Teves L, Tymianski M. Cook DJ, et al. Among authors: tymianski m. Nature. 2012 Feb 29;483(7388):213-7. doi: 10.1038/nature10841. Nature. 2012. PMID: 22388811
Here we show that stroke damage can be prevented in non-human primates in which a PSD-95 inhibitor is administered after stroke onset in clinically relevant situations. ...Our findings establish that tissue neuroprotection and improved functional outco …
Here we show that stroke damage can be prevented in non-human primates in which a PSD-95 inhibitor is administered afte …
Nonhuman primate models of stroke for translational neuroprotection research.
Cook DJ, Tymianski M. Cook DJ, et al. Among authors: tymianski m. Neurotherapeutics. 2012 Apr;9(2):371-9. doi: 10.1007/s13311-012-0115-z. Neurotherapeutics. 2012. PMID: 22437447 Free PMC article. Review.
To address potential discrepancies between rodent and human studies, the Stroke Therapy Academic Industry Roundtable (STAIR) committee suggested that nonhuman primates (NHPs) be used for preclinical, translational stroke studies. Due to the paucity of stroke …
To address potential discrepancies between rodent and human studies, the Stroke Therapy Academic Industry Roundtable (STAIR) committe …
A translational paradigm for the preclinical evaluation of the stroke neuroprotectant Tat-NR2B9c in gyrencephalic nonhuman primates.
Cook DJ, Teves L, Tymianski M. Cook DJ, et al. Among authors: tymianski m. Sci Transl Med. 2012 Oct 3;4(154):154ra133. doi: 10.1126/scitranslmed.3003824. Sci Transl Med. 2012. PMID: 23035045
Both placebo-controlled studies tested neuroprotection by Tat-NR2B9c, a prospective therapeutic compound, in anesthetized subjects. Embolic strokes were produced by small intra-arterial emboli caused by the endovascular procedure. We show that primates treated with …
Both placebo-controlled studies tested neuroprotection by Tat-NR2B9c, a prospective therapeutic compound, in anesthetized subj …
Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial.
Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M; ENACT trial investigators. Hill MD, et al. Among authors: tymianski m. Lancet Neurol. 2012 Nov;11(11):942-50. doi: 10.1016/S1474-4422(12)70225-9. Epub 2012 Oct 8. Lancet Neurol. 2012. PMID: 23051991 Clinical Trial.
BACKGROUND: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. ...FINDINGS: Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treat …
BACKGROUND: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been sh …
Advances in stroke: vascular neurosurgery.
Lanzino G, Burrows AM, Tymianski M. Lanzino G, et al. Among authors: tymianski m. Stroke. 2013 Feb;44(2):316-7. doi: 10.1161/STROKEAHA.111.000385. Epub 2013 Jan 15. Stroke. 2013. PMID: 23321447 Review. No abstract available.
Natural history and management of basilar trunk artery aneurysms.
Saliou G, Sacho RH, Power S, Kostynskyy A, Willinsky RA, Tymianski M, terBrugge KG, Rawal S, Krings T. Saliou G, et al. Among authors: tymianski m. Stroke. 2015 Apr;46(4):948-53. doi: 10.1161/STROKEAHA.114.006909. Epub 2015 Feb 24. Stroke. 2015. PMID: 25712945
There was preponderance of segmental ectasia or mural bleeding ectasia (P=0.045) in patients presenting with transit ischemic attack/stroke or mass effect. Six patients with segmental and 4 with mural bleeding ectasia demonstrated increasing size of their aneurysm, with 2 …
There was preponderance of segmental ectasia or mural bleeding ectasia (P=0.045) in patients presenting with transit ischemic attack/stro …
Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke.
Shabanzadeh AP, Tassew NG, Szydlowska K, Tymianski M, Banerjee P, Vigouroux RJ, Eubanks JH, Huang L, Geraerts M, Koeberle PD, Mueller BK, Monnier PP. Shabanzadeh AP, et al. Among authors: tymianski m. Cell Death Dis. 2015 May 7;6(5):e1744. doi: 10.1038/cddis.2015.109. Cell Death Dis. 2015. PMID: 25950474 Free PMC article.
Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association with lipid rafts. ...Thus, our results draw attention to the role of Neogenin and lipid rafts as potential targets following stroke....
Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association wit …
Neuroprotective therapies: Preclinical reproducibility is only part of the problem.
Tymianski M. Tymianski M. Sci Transl Med. 2015 Aug 5;7(299):299fs32. doi: 10.1126/scitranslmed.aac9412. Epub 2015 Aug 5. Sci Transl Med. 2015. PMID: 26246165
Among the many unknowns in the translational path to developing drugs for acute stroke, addressing the reproducibility of preclinical data is only one piece of a multifaceted and incomplete puzzle (Llovera et al., this issue)....
Among the many unknowns in the translational path to developing drugs for acute stroke, addressing the reproducibility of preclinical …
Safety, efficacy, and cost of surgery for patients with unruptured aneurysms deemed unsuitable for endovascular therapy.
Zweifel C, Sacho RH, Tymianski R, Radovanovic I, Tymianski M. Zweifel C, et al. Among authors: tymianski m. Acta Neurochir (Wien). 2015 Dec;157(12):2061-70; discussion 2070. doi: 10.1007/s00701-015-2606-2. Epub 2015 Oct 24. Acta Neurochir (Wien). 2015. PMID: 26496925
This compared favorably with the endovascular cohort in which two patients died due to treatment (mRS = 6) and one suffered a severe stroke (mRS = 5 at 6 months). CONCLUSIONS: For patients counseled to undergo treatment but have UIAs unsuitable for endovascular repair, sur …
This compared favorably with the endovascular cohort in which two patients died due to treatment (mRS = 6) and one suffered a severe stro …
Efficacy of the PSD95 inhibitor Tat-NR2B9c in mice requires dose translation between species.
Teves LM, Cui H, Tymianski M. Teves LM, et al. Among authors: tymianski m. J Cereb Blood Flow Metab. 2016 Mar;36(3):555-61. doi: 10.1177/0271678X15612099. Epub 2015 Oct 19. J Cereb Blood Flow Metab. 2016. PMID: 26661213 Free PMC article.
Tat-NR2B9c, a clinical-stage stroke neuroprotectant validated in rats and primates, was recently deemed ineffective in mice. To evaluate this discrepancy, we conducted studies in mice subjected to temporary middle cerebral artery occlusion (tMCAO) for either …
Tat-NR2B9c, a clinical-stage stroke neuroprotectant validated in rats and primates, was recently deemed ineffective in …
Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury.
Xu B, Xiao AJ, Chen W, Turlova E, Liu R, Barszczyk A, Sun CLF, Liu L, Tymianski M, Feng ZP, Sun HS. Xu B, et al. Among authors: tymianski m. Mol Neurobiol. 2016 Nov;53(9):5962-5970. doi: 10.1007/s12035-015-9488-4. Epub 2015 Oct 31. Mol Neurobiol. 2016. PMID: 26520452
NA-1 attenuates NMDA receptor-mediated neuronal cell death after stroke in multiple models and species. ...The neuroprotection and improvement in neurobehavioral outcomes conferred by NA-1 in this mouse neonatal hypoxic-ischemic injury model imp …
NA-1 attenuates NMDA receptor-mediated neuronal cell death after stroke in multiple models and species. ...The neuropro …
Translational Stroke Research: Vision and Opportunities.
Bosetti F, Koenig JI, Ayata C, Back SA, Becker K, Broderick JP, Carmichael ST, Cho S, Cipolla MJ, Corbett D, Corriveau RA, Cramer SC, Ferguson AR, Finklestein SP, Ford BD, Furie KL, Hemmen TM, Iadecola C, Jakeman LB, Janis S, Jauch EC, Johnston KC, Kochanek PM, Kohn H, Lo EH, Lyden PD, Mallard C, McCullough LD, McGavern LM, Meschia JF, Moy CS, Perez-Pinzon MA, Ramadan I, Savitz SI, Schwamm LH, Steinberg GK, Stenzel-Poore MP, Tymianski M, Warach S, Wechsler LR, Zhang JH, Koroshetz W. Bosetti F, et al. Among authors: tymianski m. Stroke. 2017 Sep;48(9):2632-2637. doi: 10.1161/STROKEAHA.117.017112. Epub 2017 Jul 27. Stroke. 2017. PMID: 28751554 Free PMC article. Review. No abstract available.
Somatic Activating KRAS Mutations in Arteriovenous Malformations of the Brain.
Nikolaev SI, Vetiska S, Bonilla X, Boudreau E, Jauhiainen S, Rezai Jahromi B, Khyzha N, DiStefano PV, Suutarinen S, Kiehl TR, Mendes Pereira V, Herman AM, Krings T, Andrade-Barazarte H, Tung T, Valiante T, Zadeh G, Tymianski M, Rauramaa T, Ylä-Herttuala S, Wythe JD, Antonarakis SE, Frösen J, Fish JE, Radovanovic I. Nikolaev SI, et al. Among authors: tymianski m. N Engl J Med. 2018 Jan 18;378(3):250-261. doi: 10.1056/NEJMoa1709449. Epub 2018 Jan 3. N Engl J Med. 2018. PMID: 29298116 Free PMC article.
BACKGROUND: Sporadic arteriovenous malformations of the brain, which are morphologically abnormal connections between arteries and veins in the brain vasculature, are a leading cause of hemorrhagic stroke in young adults and children. The genetic cause of this rare focal d …
BACKGROUND: Sporadic arteriovenous malformations of the brain, which are morphologically abnormal connections between arteries and veins in …
Targeting NMDA receptors in stroke: new hope in neuroprotection.
Wu QJ, Tymianski M. Wu QJ, et al. Among authors: tymianski m. Mol Brain. 2018 Mar 13;11(1):15. doi: 10.1186/s13041-018-0357-8. Mol Brain. 2018. PMID: 29534733 Free PMC article. Review.
NMDA (N-methyl-d-aspartate) receptors (NMDARs) play a central role in excitotoxic neuronal death caused by ischemic stroke, but NMDAR channel blockers have failed to be translated into clinical stroke treatments. ...This therapeutic approach may have fewer side effe …
NMDA (N-methyl-d-aspartate) receptors (NMDARs) play a central role in excitotoxic neuronal death caused by ischemic stroke, but NMDAR …
Discovery and development of NA-1 for the treatment of acute ischemic stroke.
Ballarin B, Tymianski M. Ballarin B, et al. Among authors: tymianski m. Acta Pharmacol Sin. 2018 May;39(5):661-668. doi: 10.1038/aps.2018.5. Epub 2018 Mar 22. Acta Pharmacol Sin. 2018. PMID: 29565039 Free PMC article. Review.
Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative stress and apoptosis. There are very few treatments that have been shown to be beneficial in acute stroke. Recent findings have provid …
Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative s …
Advances in Stroke 2017.
Bernhardt J, Zorowitz RD, Becker KJ, Keller E, Saposnik G, Strbian D, Dichgans M, Woo D, Reeves M, Thrift A, Kidwell CS, Olivot JM, Goyal M, Pierot L, Bennett DA, Howard G, Ford GA, Goldstein LB, Planas AM, Yenari MA, Greenberg SM, Pantoni L, Amin-Hanjani S, Tymianski M. Bernhardt J, et al. Among authors: tymianski m. Stroke. 2018 May;49(5):e174-e199. doi: 10.1161/STROKEAHA.118.021380. Epub 2018 Apr 18. Stroke. 2018. PMID: 29669874 Review. No abstract available.
Long-term changes in cerebrovascular reactivity following EC-IC bypass for intracranial steno-occlusive disease.
Rosen C, McKetton L, Russell J, Sam K, Poublanc J, Crawley A, Han JS, Sobczyk O, Duffin J, Mandell DM, Tymianski M, Fisher JA, Mikulis DJ, Venkatraghavan L. Rosen C, et al. Among authors: tymianski m. J Clin Neurosci. 2018 Aug;54:77-82. doi: 10.1016/j.jocn.2018.06.009. Epub 2018 Jun 12. J Clin Neurosci. 2018. PMID: 29907385
Hence, in the postoperative follow-up of patients routine functional imaging to monitor cerebral hemodynamics may be useful as the risk of stroke and cognitive decline remain present with impaired CVR....
Hence, in the postoperative follow-up of patients routine functional imaging to monitor cerebral hemodynamics may be useful as the risk of …
Deep Brain Stimulation Rescues Memory and Synaptic Activity in a Rat Model of Global Ischemia.
Gondard E, Teves L, Wang L, McKinnon C, Hamani C, Kalia SK, Carlen PL, Tymianski M, Lozano AM. Gondard E, et al. Among authors: tymianski m. J Neurosci. 2019 Mar 27;39(13):2430-2440. doi: 10.1523/JNEUROSCI.1222-18.2019. Epub 2019 Jan 29. J Neurosci. 2019. PMID: 30696731 Free PMC article.
Ischemic stroke is responsible for a large number of neurological deficits including memory impairment. ...Novel approaches to improve neurological outcomes after stroke are urgently needed; therefore, the present study highlights a possible role for DBS in the trea …
Ischemic stroke is responsible for a large number of neurological deficits including memory impairment. ...Novel approaches to improv …
The impact of postsynaptic density 95 blocking peptide (Tat-NR2B9c) and an iNOS inhibitor (1400W) on proteomic profile of the hippocampus in C57BL/6J mouse model of kainate-induced epileptogenesis.
Tse K, Hammond D, Simpson D, Beynon RJ, Beamer E, Tymianski M, Salter MW, Sills GJ, Thippeswamy T. Tse K, et al. Among authors: tymianski m. J Neurosci Res. 2019 Nov;97(11):1378-1392. doi: 10.1002/jnr.24441. Epub 2019 May 15. J Neurosci Res. 2019. PMID: 31090233 Free PMC article.
In addition, we have incorporated two putative antiepileptogenic drugs, postsynaptic density protein-95 blocking peptide (PSD95BP or Tat-NR2B9c) and a highly selective inducible nitric oxide synthase inhibitor, 1400W, to give an insight into how such agents might am …
In addition, we have incorporated two putative antiepileptogenic drugs, postsynaptic density protein-95 blocking peptide (PSD95BP or Tat …
Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.
Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, van Adel BA, Swartz RH, Shah RA, Sauvageau E, Zerna C, Ospel JM, Joshi M, Almekhlafi MA, Ryckborst KJ, Lowerison MW, Heard K, Garman D, Haussen D, Cutting SM, Coutts SB, Roy D, Rempel JL, Rohr AC, Iancu D, Sahlas DJ, Yu AYX, Devlin TG, Hanel RA, Puetz V, Silver FL, Campbell BCV, Chapot R, Teitelbaum J, Mandzia JL, Kleinig TJ, Turkel-Parrella D, Heck D, Kelly ME, Bharatha A, Bang OY, Jadhav A, Gupta R, Frei DF, Tarpley JW, McDougall CG, Holmin S, Rha JH, Puri AS, Camden MC, Thomalla G, Choe H, Phillips SJ, Schindler JL, Thornton J, Nagel S, Heo JH, Sohn SI, Psychogios MN, Budzik RF, Starkman S, Martin CO, Burns PA, Murphy S, Lopez GA, English J, Tymianski M; ESCAPE-NA1 Investigators. Hill MD, et al. Among authors: tymianski m. Lancet. 2020 Mar 14;395(10227):878-887. doi: 10.1016/S0140-6736(20)30258-0. Epub 2020 Feb 20. Lancet. 2020. PMID: 32087818 Clinical Trial.
BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia …
BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in pr …
Final Results of the Prospective Multicenter Excimer Laser-Assisted High-Flow Bypass Study on the Treatment of Giant Anterior Circulation Aneurysms.
van der Zwan A, Vajkoczy P, Amin-Hanjani S, Charbel FT, Welch B, Tymianski M, Kivipelto L, van Thoor S, Chakraborty S, O'Donnell D, Langer DJ. van der Zwan A, et al. Among authors: tymianski m. Neurosurgery. 2020 Sep 15;87(4):697-703. doi: 10.1093/neuros/nyz489. Neurosurgery. 2020. PMID: 31748798 Clinical Trial.
Four patients had remaining neurological deficits after 30 d caused by stroke (11.4%). These strokes were not related to the ELANA anastomosis device. CONCLUSION: This study does not prove that the ELANA technique has an advantage over conventional bypass techniques, but i …
Four patients had remaining neurological deficits after 30 d caused by stroke (11.4%). These strokes were not related to the ELANA an …
Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection.
Menon BK, Ospel JM, McTaggart RA, Nogueira RG, Demchuk AM, Poppe A, Rempel JL, Zerna C, Joshi M, Almekhlafi MA, Field TS, Dowlatshahi D, van Adel BA, Sauvageau E, Tarpley J, Moreira T, Bang OY, Heck D, Psychogios MN, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 investigators. Menon BK, et al. Among authors: tymianski m. J Neurointerv Surg. 2020 Nov 25:neurintsurg-2020-016902. doi: 10.1136/neurintsurg-2020-016902. Online ahead of print. J Neurointerv Surg. 2020. PMID: 33239306
BACKGROUND: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on no …
BACKGROUND: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients present …
Plasmin-resistant PSD-95 inhibitors resolve effect-modifying drug-drug interactions between alteplase and nerinetide in acute stroke.
Mayor-Nunez D, Ji Z, Sun X, Teves L, Garman JD, Tymianski M. Mayor-Nunez D, et al. Among authors: tymianski m. Sci Transl Med. 2021 Apr 7;13(588):eabb1498. doi: 10.1126/scitranslmed.abb1498. Sci Transl Med. 2021. PMID: 33827973
Neuroprotection for acute ischemic stroke is achievable with the eicosapeptide nerinetide, an inhibitor of the protein-protein interactions of the synaptic scaffolding protein PSD-95. ...Our data suggest that both the clinical-stage PSD-95 inhib …
Neuroprotection for acute ischemic stroke is achievable with the eicosapeptide nerinetide, an inhibitor of the protein-protein intera …
Iatrogenic Diffusion-Weighted Imaging Lesions: What Is Their Impact and How Can It Be Measured?
Goyal M, Ganesh A, Tymianski M, Hill MD, Ospel JM. Goyal M, et al. Among authors: tymianski m. Stroke. 2021 May;52(5):1929-1936. doi: 10.1161/STROKEAHA.120.033984. Epub 2021 Apr 8. Stroke. 2021. PMID: 33827240
Infarct volume in acute ischemic stroke is closely linked with clinical outcome, with larger infarct volumes being associated with a worse prognosis. ...In this article, we describe the current limitations of our understanding of the significance of iatrogenic diffusion-we …
Infarct volume in acute ischemic stroke is closely linked with clinical outcome, with larger infarct volumes being associated with a …
A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.
Ospel JM, Menon BK, Qiu W, Kashani N, Mayank A, Singh N, Cimflova P, Marko M, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Zerna C, Joshi M, Almekhlafi MA, Haussen D, Cutting S, Coutts SB, Roy D, Rohr A, Iancu D, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Ospel JM, et al. Among authors: tymianski m. Radiology. 2021 Jul;300(1):152-159. doi: 10.1148/radiol.2021203964. Epub 2021 May 11. Radiology. 2021. PMID: 33973838 Clinical Trial.
Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with …
Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To invest …
Radiologic Patterns of Intracranial Hemorrhage and Clinical Outcome after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.
Ospel JM, Qiu W, Menon BK, Mayank A, Demchuk A, McTaggart R, Nogueira RG, Poppe AY, Jayaraman M, Buck B, Haussen D, Roy D, Joshi M, Zerna C, Almekhlafi M, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Ospel JM, et al. Among authors: tymianski m. Radiology. 2021 Aug;300(2):402-409. doi: 10.1148/radiol.2021204560. Epub 2021 Jun 1. Radiology. 2021. PMID: 34060942 Clinical Trial.
Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the …
Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to …
Strength of Association between Infarct Volume and Clinical Outcome Depends on the Magnitude of Infarct Size: Results from the ESCAPE-NA1 Trial.
Ospel JM, Hill MD, Menon BK, Demchuk A, McTaggart R, Nogueira R, Poppe A, Haussen D, Qiu W, Mayank A, Almekhlafi M, Zerna C, Joshi M, Jayaraman M, Roy D, Rempel J, Buck B, Tymianski M, Goyal M; ESCAPE-NA1 investigators. Ospel JM, et al. Among authors: tymianski m. AJNR Am J Neuroradiol. 2021 Aug;42(8):1375-1379. doi: 10.3174/ajnr.A7183. Epub 2021 Jun 24. AJNR Am J Neuroradiol. 2021. PMID: 34167959 Free PMC article. Clinical Trial.
BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the S …
BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the associ …
Clinical outcomes of isolated deep grey matter infarcts after endovascular treatment of large vessel occlusion stroke.
Ospel J, Mayank A, Qiu W, Almekhlafi M, Menon B, McTaggart R, Nogueira R, Demchuk A, Joshi M, Zerna C, Chapot R, Bharatha A, Jadhav A, Nagel S, Poppe A, Tymianski M, Hill M, Goyal M; ESCAPE-NA1 investigators. Ospel J, et al. Among authors: tymianski m. Neuroradiology. 2021 Sep;63(9):1463-1469. doi: 10.1007/s00234-021-02656-4. Epub 2021 Feb 2. Neuroradiology. 2021. PMID: 33528624
PURPOSE: There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome. ...
PURPOSE: There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we a …
Reassessing Alberta Stroke Program Early CT Score on Non-Contrast CT Based on Degree and Extent of Ischemia.
Ospel JM, Menon BK, Marko M, Mayank A, Ganesh A, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Joshi M, Almekhlafi MA, Zerna C, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 investigators. Ospel JM, et al. Among authors: tymianski m. J Stroke. 2021 Sep;23(3):440-442. doi: 10.5853/jos.2021.00458. Epub 2021 Sep 30. J Stroke. 2021. PMID: 34649388 Free PMC article. No abstract available.
Clinical impact of EVT with failed reperfusion in patients with acute ischemic stroke: results from the ESCAPE and ESCAPE-NA1 trials.
Ospel JM, Hill MD, Demchuk A, Menon BK, Thornton J, Rempel J, Almekhlafi MA, Ganesh A, Kappelhof M, Singh N, Cimflova P, Kashani N, Bala F, Kim BJ, McTaggart R, Poppe A, Nogueira RG, Tymianski M, Goyal M. Ospel JM, et al. Among authors: tymianski m. Neuroradiology. 2021 Nov;63(11):1883-1889. doi: 10.1007/s00234-021-02723-w. Epub 2021 Apr 29. Neuroradiology. 2021. PMID: 33914135
BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized th …
BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion c …
Assessment of Discrepancies Between Follow-up Infarct Volume and 90-Day Outcomes Among Patients With Ischemic Stroke Who Received Endovascular Therapy.
Ganesh A, Ospel JM, Menon BK, Demchuk AM, McTaggart RA, Nogueira RG, Poppe AY, Almekhlafi MA, Hanel RA, Thomalla G, Holmin S, Puetz V, van Adel BA, Tarpley JW, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Trial Investigators. Ganesh A, et al. Among authors: tymianski m. JAMA Netw Open. 2021 Nov 1;4(11):e2132376. doi: 10.1001/jamanetworkopen.2021.32376. JAMA Netw Open. 2021. PMID: 34739060 Free PMC article.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter t …
DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing …
Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial.
Ganesh A, Goyal M, Wilson AT, Ospel JM, Demchuk AM, Mikulis D, Poublanc J, Krings T, Anderson R, Tymianski M, Hill MD; ENACT Trial Investigators. Ganesh A, et al. Among authors: tymianski m. Neurology. 2022 Apr 5;98(14):e1446-e1458. doi: 10.1212/WNL.0000000000200111. Epub 2022 Feb 15. Neurology. 2022. PMID: 35169007 Clinical Trial.
METHODS: In this post hoc analysis, we used multivariable models to evaluate the association of the presence and number of iatrogenic infarcts on DWI with neurologic impairment (NIH Stroke Scale [NIHSS]), functional status (modified Rankin Scale [mRS]), and cognitive and n …
METHODS: In this post hoc analysis, we used multivariable models to evaluate the association of the presence and number of iatrogenic infarc …
Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.
Marko M, Cimflova P, Poppe AY, Kashani N, Singh N, Ospel J, Mayank A, van Adel B, McTaggart RA, Nogueira RG, Demchuk AM, Rempel JL, Joshi M, Zerna C, Menon BK, Tymianski M, Hill MD, Goyal M, Almekhlafi MA; ESCAPE-NA1 investigators. Marko M, et al. Among authors: tymianski m. J Neurointerv Surg. 2022 May;14(5):neurintsurg-2021-017474. doi: 10.1136/neurintsurg-2021-017474. Epub 2021 May 4. J Neurointerv Surg. 2022. PMID: 33947770 Clinical Trial.
BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial. ...CONCLUSIONS: Tandem cervical carotid occlusion in …
BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed o …
Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.
Ospel JM, McDonough R, Demchuk AM, Menon BK, Almekhlafi MA, Nogueira RG, McTaggart RA, Poppe AY, Buck BH, Roy D, Haussen DC, Chapot R, Field TS, Jayaraman MV, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 investigators. Ospel JM, et al. Among authors: tymianski m. J Neurointerv Surg. 2022 Sep;14(9):886-891. doi: 10.1136/neurintsurg-2021-017994. Epub 2021 Sep 7. J Neurointerv Surg. 2022. PMID: 34493575
BACKGROUND: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication. ...Collateral status (beta: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score …
BACKGROUND: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-m …
Association of Stent-Retriever Characteristics in Establishing Successful Reperfusion During Mechanical Thrombectomy : Results from the ESCAPE-NA1 Trial.
Cimflova P, Singh N, Ospel JM, Marko M, Kashani N, Mayank A, Hanel R, Haussen DC, Bharatha A, Volders D, Heran MKS, Poppe AY, van Adel B, Menon BK, Joshi M, Demchuk A, McTaggart R, Nogueira RG, Rempel JL, Zerna C, Tymianski M, Hill MD, Goyal M, Almekhlafi MA. Cimflova P, et al. Among authors: tymianski m. Clin Neuroradiol. 2022 Sep;32(3):799-807. doi: 10.1007/s00062-021-01123-0. Epub 2022 Jan 7. Clin Neuroradiol. 2022. PMID: 34993582 Clinical Trial.
How can imaging in acute ischemic stroke help us to understand tissue fate in the era of endovascular treatment and cerebroprotection?
Goyal M, McTaggart R, Ospel JM, van der Lugt A, Tymianski M, Wiest R, Lundberg J, von Kummer R, Hill MD, Luijten S, Roozenbeek B, Saver JL, McDonough RV. Goyal M, et al. Among authors: tymianski m. Neuroradiology. 2022 Sep;64(9):1697-1707. doi: 10.1007/s00234-022-03001-z. Epub 2022 Jul 20. Neuroradiology. 2022. PMID: 35854136 No abstract available.
Mice and Rats Exhibit Striking Inter-species Differences in Gene Response to Acute Stroke.
Wu QJ, Sun X, Teves L, Mayor D, Tymianski M. Wu QJ, et al. Among authors: tymianski m. Cell Mol Neurobiol. 2022 Nov;42(8):2773-2789. doi: 10.1007/s10571-021-01138-8. Epub 2021 Aug 5. Cell Mol Neurobiol. 2022. PMID: 34350530
Neuroprotection in acute stroke has not been successfully translated from animals to humans. Animal research on promising agents continues largely in rats and mice which are commonly available to researchers. ...The findings of this study may have significant implications …
Neuroprotection in acute stroke has not been successfully translated from animals to humans. Animal research on promising agents cont …
Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.
Singh N, Cimflova P, Ospel JM, Kashani N, Marko M, Mayank A, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Field TS, Dowlatshahi D, van Adel B, Swartz RH, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, Goyal M, Almekhlafi MA, Hill MD; ESCAPE-NA1 Trial Investigators. Singh N, et al. Among authors: tymianski m. Stroke. 2023 Jun;54(6):1477-1483. doi: 10.1161/STROKEAHA.122.042200. Epub 2023 Apr 21. Stroke. 2023. PMID: 37082967 Free article. Clinical Trial.
BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA …
BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT …
Health economic impact of Nerinetide in addition to mechanical thrombectomy without concurrent alteplase.
Ospel JM, Adams C, Tymianski M, Goyal M, Hill M. Ospel JM, et al. Among authors: tymianski m. Interv Neuroradiol. 2023 Aug 17:15910199231193455. doi: 10.1177/15910199231193455. Online ahead of print. Interv Neuroradiol. 2023. PMID: 37590087
BACKGROUND AND PURPOSE: The ESCAPE-NA1 trial has shown that intravenous Nerinetide improves clinical outcomes in acute ischemic stroke patients with large vessel occlusion undergoing endovascular treatment without concurrent intravenous alteplase. ...METHODS: Data are from …
BACKGROUND AND PURPOSE: The ESCAPE-NA1 trial has shown that intravenous Nerinetide improves clinical outcomes in acute ischemic stroke …
CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.
Rex NB, McDonough RV, Ospel JM, Kashani N, Sehgal A, Fladt JC, McTaggart RA, Nogueira R, Menon B, Demchuk AM, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Rex NB, et al. Among authors: tymianski m. AJNR Am J Neuroradiol. 2023 Sep;44(9):1045-1049. doi: 10.3174/ajnr.A7954. Epub 2023 Aug 24. AJNR Am J Neuroradiol. 2023. PMID: 37620153 Free PMC article.
BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinic …
BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing e …
Cortical and Subcortical Brain Atrophy Assessment Using Simple Measures on NCCT Compared with MRI in Acute Stroke.
Jaroenngarmsamer T, Benali F, Fladt J, Singh N, Bala F, Tymianski M, Hill MD, Goyal M, Ganesh A; ESCAPE-NA1 Investigators. Jaroenngarmsamer T, et al. Among authors: tymianski m. AJNR Am J Neuroradiol. 2023 Oct;44(10):1144-1149. doi: 10.3174/ajnr.A7981. Epub 2023 Aug 31. AJNR Am J Neuroradiol. 2023. PMID: 37652580 Free PMC article.
BACKGROUND AND PURPOSE: Brain atrophy is an important surrogate for brain reserve, the capacity of the brain to cope with acquired injuries such as acute stroke. It is unclear how well atrophy measurements on MR imaging can be reproduced using NCCT imaging. We aimed to com …
BACKGROUND AND PURPOSE: Brain atrophy is an important surrogate for brain reserve, the capacity of the brain to cope with acquired injuries …
Association of Brain Atrophy With Functional Outcome and Recovery Trajectories After Thrombectomy: Post Hoc Analysis of the ESCAPE-NA1 Trial.
Benali F, Fladt J, Jaroenngarmsamer T, Bala F, Singh N, Ospel JM, Tymianski M, Hill MD, Goyal M, Ganesh A. Benali F, et al. Among authors: tymianski m. Neurology. 2023 Oct 10;101(15):e1521-e1530. doi: 10.1212/WNL.0000000000207700. Epub 2023 Aug 17. Neurology. 2023. PMID: 37591777 Free PMC article. Clinical Trial.
BACKGROUND AND OBJECTIVES: Brain frailty may impair the ability of acute stroke patients to cope with the injury, irrespective of their chronologic age, resulting in impaired recovery. ...Adjustments were made for age, sex, baseline NIHSS, final infarct volume, stroke …
BACKGROUND AND OBJECTIVES: Brain frailty may impair the ability of acute stroke patients to cope with the injury, irrespective of the …
Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.
Marko M, Goyal M, Ospel JM, Singh N, Venema E, Nogueira RG, Demchuk AM, McTaggart RA, Poppe AY, Menon BK, Zerna C, Mulder M, Dippel DW, Lingsma HF, Roozenbeek B, Tymianski M, Hill MD. Marko M, et al. Among authors: tymianski m. Interv Neuroradiol. 2023 Dec 20:15910199231221491. doi: 10.1177/15910199231221491. Online ahead of print. Interv Neuroradiol. 2023. PMID: 38115793 Free article.
BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate …
BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differenc …
Brain Stress Test for Assessing Risk for Hemodynamic Stroke.
Venkatraghavan L, Rosen C, McKetton L, Poublanc J, Sobczyk O, Duffin J, Tymianski M, Fisher JA, Mikulis DJ. Venkatraghavan L, et al. Among authors: tymianski m. Can J Neurol Sci. 2024 Jan;51(1):57-63. doi: 10.1017/cjn.2023.3. Epub 2023 Jan 10. Can J Neurol Sci. 2024. PMID: 36624923
BACKGROUND: In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. ...Impaired CVR is associated with a higher incide …
BACKGROUND: In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic v …
Mediation of Age and Thrombectomy Outcome by Neuroimaging Markers of Frailty in Patients With Stroke.
Benali F, Singh N, Fladt J, Jaroenngarmsamer T, Bala F, Ospel JM, Buck BH, Dowlatshahi D, Field TS, Hanel RA, Peeling L, Tymianski M, Hill MD, Goyal M, Ganesh A; ESCAPE-NA1 Investigators. Benali F, et al. Among authors: tymianski m. JAMA Netw Open. 2024 Jan 2;7(1):e2349628. doi: 10.1001/jamanetworkopen.2023.49628. JAMA Netw Open. 2024. PMID: 38165676 Free PMC article. Clinical Trial.
OBJECTIVES: To explore the mediation of age on functional outcome by neuroimaging markers of frailty (hereinafter neuroimaging frailty) in patients with acute ischemic stroke receiving endovascular thrombectomy (EVT). DESIGN, SETTING, AND PARTICIPANTS: This cohort study wa …
OBJECTIVES: To explore the mediation of age on functional outcome by neuroimaging markers of frailty (hereinafter neuroimaging frailty) in p …
Infarct Evolution on MR-DWI After Thrombectomy in Acute Stroke Patients Randomized to Nerinetide or Placebo: The REPERFUSE-NA1 Study.
Fladt J, Guo J, Specht JL, Wang M, Chan LL, Mctaggart R, Buck BH, Aviv R, Swartz RH, Field TS, Tarpley J, Shah R, Goyal M, Tymianski M, Hill MD, Demchuk A, d'Esterre C, Barber P. Fladt J, et al. Among authors: tymianski m. Neurology. 2024 Jan 23;102(2):e207976. doi: 10.1212/WNL.0000000000207976. Epub 2023 Dec 22. Neurology. 2024. PMID: 38165335 Clinical Trial.
DISCUSSION: This study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acute stroke treatment. Patients with acute large vessel occlusive stroke exhibited appreciable early infarct growth both in the g …
DISCUSSION: This study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acut …
Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.
van Niftrik CHB, Sebök M, Germans MR, Halter M, Pokorny T, Stumpo V, Bellomo J, Piccirelli M, Pangalu A, Katan M, Wegener S, Tymianski M, Kulcsár Z, Luft AR, Fisher JA, Mikulis DJ, Regli L, Fierstra J. van Niftrik CHB, et al. Among authors: tymianski m. Stroke. 2024 Mar;55(3):613-621. doi: 10.1161/STROKEAHA.123.044259. Epub 2024 Feb 8. Stroke. 2024. PMID: 38328926 Free article.
Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. ...Risk factors associated with an increase …
Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was ass …
Prevalence of "Ghost Infarct Core" after Endovascular Thrombectomy.
Ospel JM, Rex N, Rinkel L, Kashani N, Buck B, Rempel J, Sahlas D, Kelly ME, Budzik R, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Ospel JM, et al. Among authors: tymianski m. AJNR Am J Neuroradiol. 2024 Mar 7;45(3):291-295. doi: 10.3174/ajnr.A8113. AJNR Am J Neuroradiol. 2024. PMID: 38272571
MATERIALS AND METHODS: Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergoing endovascular treatment were randomized to intravenous nerinetide or placebo. ...
MATERIALS AND METHODS: Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergo …
Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.
Ospel JM, Rinkel L, Ganesh A, Demchuk A, Joshi M, Poppe A, McTaggart R, Nogueira R, Menon B, Tymianski M, Hill MD, Goyal M. Ospel JM, et al. Among authors: tymianski m. Stroke. 2024 May;55(5):1349-1358. doi: 10.1161/STROKEAHA.123.045825. Epub 2024 Mar 21. Stroke. 2024. PMID: 38511330
BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook N …
BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Mont …
How Do Quantitative Tissue Imaging Outcomes in Acute Ischemic Stroke Relate to Clinical Outcomes?
Ospel JM, Rinkel L, Ganesh A, Demchuk A, Heran M, Sauvageau E, Joshi M, Haussen D, Jayaraman M, Coutts S, Yu A, Puetz V, Iancu D, Bang OY, Tarpley J, Holmin S, Kelly M, Tymianski M, Hill M, Goyal M; ESCAPE-NA1 Investigators. Ospel JM, et al. Among authors: tymianski m. J Stroke. 2024 May;26(2):252-259. doi: 10.5853/jos.2023.02180. Epub 2024 May 30. J Stroke. 2024. PMID: 38836272 Free PMC article.
BACKGROUND AND PURPOSE: Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclea …
BACKGROUND AND PURPOSE: Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute i …
Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.
Marko M, Singh N, Ospel JM, Uchida K, Almekhlafi MA, Demchuk AM, Nogueira RG, McTaggart RA, Poppe AY, Rempel JL, Tymianski M, Hill MD, Goyal M, Menon BK; ESCAPE-NA1 Investigators. Marko M, et al. Among authors: tymianski m. Clin Neuroradiol. 2024 Jun;34(2):333-339. doi: 10.1007/s00062-023-01365-0. Epub 2023 Dec 18. Clin Neuroradiol. 2024. PMID: 38108829 Free PMC article. Clinical Trial.
PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilate …
PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic s …
Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke.
Joundi RA, Smith EE, Ganesh A, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Field TS, Dowlatshahi D, Sahlas J, Swartz R, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, Goyal M, Hill MD; ESCAPE-NA1 Investigators. Joundi RA, et al. Among authors: tymianski m. JAMA Neurol. 2024 Jul 1;81(7):752-761. doi: 10.1001/jamaneurol.2024.1562. JAMA Neurol. 2024. PMID: 38829660 Clinical Trial.
IMPORTANCE: The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. OBJECTIVE: To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke …
IMPORTANCE: The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unkn …
Effect of incomplete reperfusion patterns on clinical outcome: insights from the ESCAPE-NA1 trial.
Cimflova P, Singh N, Kappelhof M, Ospel JM, Sehgal A, Kashani N, Almekhlafi MA, Demchuk AM, Berrouschot J, Dorn F, Kelly ME, Buck BH, Field TS, Dowlatshahi D, Tymianski M, Hill MD, Goyal M. Cimflova P, et al. Among authors: tymianski m. J Neurointerv Surg. 2024 Jul 16;16(8):809-814. doi: 10.1136/jnis-2023-020553. J Neurointerv Surg. 2024. PMID: 37491383 Clinical Trial.
Cytoprotective agents in stroke: Still uncertainty in the next frontier.
Siddiqi AZ, Kashani N, Dmytriw AA, Yavagal DR, Saposnik G, Tymianski M, Adams C, Hill MD, Dowlatshahi D, Katsanos AH, Menon BK, Ganesh A, Singh N. Siddiqi AZ, et al. Among authors: tymianski m. J Stroke Cerebrovasc Dis. 2024 Sep;33(9):107860. doi: 10.1016/j.jstrokecerebrovasdis.2024.107860. Epub 2024 Jul 11. J Stroke Cerebrovasc Dis. 2024. PMID: 38997049 Free article.
INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. ...Respondents w …
INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intrav …
Understanding physician preferences about combined thrombolysis and thrombectomy in patients with large vessel occlusion: An international cross-sectional survey.
Siddiqi AZ, Kashani N, Dmytriw AA, Yavagal D, Saposnik G, Tymianski M, Adams C, Hill MD, Dowlatshahi D, Katsanos AH, Menon BK, Ganesh A, Singh N. Siddiqi AZ, et al. Among authors: tymianski m. J Stroke Cerebrovasc Dis. 2024 Dec;33(12):108022. doi: 10.1016/j.jstrokecerebrovasdis.2024.108022. Epub 2024 Sep 19. J Stroke Cerebrovasc Dis. 2024. PMID: 39306059 Free article.
In each scenario, a patient was presenting with an AIS with LVO, varying a single clinical or imaging feature. RESULTS: A total of 282 stroke physicians (mean age 46 years, 75 % males) participated in the survey. In LVO stroke, eligible for both IVT and EVT, without …
In each scenario, a patient was presenting with an AIS with LVO, varying a single clinical or imaging feature. RESULTS: A total of 282 st …
Effects of reperfusion grade and reperfusion strategy on the clinical outcome: Insights from ESCAPE-NA1 trial.
Cimflova P, Ospel JM, Singh N, Marko M, Kashani N, Mayank A, Demchuk A, Menon B, Poppe AY, Nogueira R, McTaggart R, Rempel JL, Tymianski M, Hill MD, Almekhlafi MA, Goyal M. Cimflova P, et al. Among authors: tymianski m. Interv Neuroradiol. 2024 Dec;30(6):804-811. doi: 10.1177/15910199241288874. Epub 2024 Oct 14. Interv Neuroradiol. 2024. PMID: 39397754 Free PMC article. Clinical Trial.
Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.
Ospel JM, Goyal M, Menon BK, Almekhlafi MA, Zerna C, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Joshi M, Kashani N, Heard K, Field TS, Dowlatshahi D, van Adel B, Swartz RH, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, Hill MD; ESCAPE-NA1 Investigators. Ospel JM, et al. Among authors: tymianski m. Stroke. 2024 Dec 9. doi: 10.1161/STROKEAHA.124.048601. Online ahead of print. Stroke. 2024. PMID: 39648909
METHODS: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo. ...Other pred …
METHODS: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Pro …