Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies

Exp Neurol. 2021 Jan:335:113518. doi: 10.1016/j.expneurol.2020.113518. Epub 2020 Nov 2.


Stroke is the leading cause of disability and thesecond leading cause of death worldwide. With the global population aged 65 and over growing faster than all other age groups, the incidence of stroke is also increasing. In addition, there is a shift in the overall stroke burden towards younger age groups, particularly in low and middle-income countries. Stroke in most cases is caused due to an abrupt blockage of an artery (ischemic stroke), but in some instances stroke may be caused due to bleeding into brain tissue when a blood vessel ruptures (hemorrhagic stroke). Although treatment options for stroke are still limited, with the advancement in recanalization therapy using both pharmacological and mechanical thrombolysis some progress has been made in helping patients recover from ischemic stroke. However, there is still a substantial need for the development of therapeutic agents for neuroprotection in acute ischemic stroke to protect the brain from damage prior to and during recanalization, extend the therapeutic time window for intervention and further improve functional outcome. The current review has assessed the past challenges in developing neuroprotective strategies, evaluated the recent advances in clinical trials, discussed the recent initiative by the National Institute of Neurological Disorders and Stroke in USA for the search of novel neuroprotectants (Stroke Preclinical Assessment Network, SPAN) and identified emerging neuroprotectants being currently evaluated in preclinical studies. The underlying molecular mechanism of each of the neuroprotective strategies have also been summarized, which could assist in the development of future strategies for combinational therapy in stroke treatment.

Keywords: Blood-brain barrier dysfunction; Clinical trials; Comorbidities; Excitotoxicity; Ischemic stroke; Neuroinflammation; Neuroprotection; Neuroprotective agents; Oxidative stress; Preclinical studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Humans
  • Ischemic Stroke / drug therapy
  • Ischemic Stroke / therapy*
  • Neuroprotection*
  • Neuroprotective Agents / therapeutic use


  • Neuroprotective Agents