Neuroprotective potential of solanesol in a combined model of intracerebral and intraventricular hemorrhage in rats

Kajal Rajdev; Ehraz Mehmood Siddiqui; Kuldeep Singh Jadaun; Sidharth Mehan

doi:10.1016/j.ibror.2020.03.001

Neuroprotective potential of solanesol in a combined model of intracerebral and intraventricular hemorrhage in rats

IBRO Rep. 2020 Apr 22:8:101-114. doi: 10.1016/j.ibror.2020.03.001. eCollection 2020 Jun.

Authors

Kajal Rajdev¹, Ehraz Mehmood Siddiqui¹, Kuldeep Singh Jadaun¹, Sidharth Mehan¹

Affiliation

¹ Neuropharmacology Division, ISF College of Pharmacy, Moga, 142001 Punjab, India.

Abstract

Intracerebral hemorrhage (ICH) may be caused by trauma, aneurysm and arteriovenous malformation, as can any bleeding within the intracranial vault, including brain parenchyma and adjacent meningeal spaces (aneurism and atreovenous malformation). ICH is the cerebral stroke with the least treatable form. Over time, intraventricular hemorrhage (IVH) is associated with ICH, which contributes to hydrocephalus, and the major cause of most hemorrhagic death (Due to the cerebral hemorrhage and post hemorrhagic surgeries). Most patients suffer from memory impairment, grip strength, posture, and cognitive dysfunctions attributable to cerebral hemorrhage or post-brain hemorrhagic surgery. Nevertheless, a combined model of ICH based IVH is not present pre-clinically. Autologous blood (ALB) injection (20 μl/5 min) in the rat brain triggers hemorrhage, such as factors that further interfere with the normal functioning of neuroinflammatory cytokines, oxidative stress, and neurotransmitter dysfunction, such as CoQ10 insufficiency and dysregulation of mitochondrial ETC-complexes. For the prevention of post-brain hemorrhagic behavioral and neurochemical dysfunctions, there is no specific drug treatment available, only available therapy used to provide symptomatic relief. The current study reveals that long-term administration of Solanesol (SNL) 40 and 60 mg/kg alone and in combination with available drug therapy Donepezil (DNP) 3 mg/kg, Memantine (MEM) 20 mg/kg, Celecoxib (CLB) 20 mg/kg, Pregabalin (PGB) 30 mg/kg, may provide the neuroprotective effect by improving behavioral and neurochemical deficits, and gross pathological changes in ALB induced combined experimental model of ICH-IVH in post brain hemorrhagic conditions in rats. Thus, SNL can be a potential therapeutic approach to improve neuronal mitochondrial dysfunction associated with post brain hemorrhagic behavioral and neurochemical alterations.

Keywords: Celecoxib; Intracerebral-Intraventricular hemorrhage; Memantine; Mitochondrial dysfunction; Oxidative stress; Pregabalin; Solanesol.