Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Jun 1;11(2):81-97.
doi: 10.2174/187152411796011321.

Central nervous system agents for ischemic stroke: neuroprotection mechanisms

Rachna S Pandya  1 , Lijuan Mao, Hua Zhou, Shuanhu Zhou, Jiang Zeng, A John Popp, Xin Wang
Affiliations
Review

Central nervous system agents for ischemic stroke: neuroprotection mechanisms

Rachna S Pandya et al. Cent Nerv Syst Agents Med Chem. .

Abstract

Stroke is the third leading cause of mortality and disability in the United States. Ischemic stroke constitutes 85% of all stroke cases. However, no effective treatment has been found to prevent damage to the brain in such cases except tissue plasminogen activator with narrow therapeutic window, and there is an unmet need to develop therapeutics for neuroprotection from ischemic stroke. Studies have shown that mechanisms including apoptosis, necrosis, inflammation, immune modulation, and oxidative stress and mediators such as excitatory amino acids, nitric oxide, inflammatory mediators, neurotransmitters, reactive oxygen species, and withdrawal of trophic factors may lead to the development of the ischemic cascade. Hence, it is essential to develop neuroprotective agents targeting either the mechanisms or the mediators leading to development of ischemic stroke. This review focuses on central nervous system agents targeting these biochemical pathways and mediators of ischemic stroke, mainly those that counteract apoptosis, inflammation, and oxidation, and well as glutamate inhibitors which have been shown to provide neuroprotection in experimental animals. All these agents have been shown to improve neurological outcome after ischemic insult in experimental animals in vivo, organotypic brain slice/acute slice ex vivo, and cell cultures in vitro and may therefore aid in preventing long-term morbidity and mortality associated with ischemic stroke.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1). Summary of CNS agents for ischemic stroke with neuroprotective mechanisms
Ischemic stroke is mediated by various mechanisms including oxidative stress through formation of free radicals and reactive oxygen species, apoptosis, inflammation, excitotoxicity by glutamate and other extracellular aminoacids, overlapping each other, forming a reversible ischemic penumbra and an irreversible infarct core. Agents acting on these mechanisms may prove to be neuroprotective in ischemic stroke.
Fig. (2)
Fig. (2). Cerebral ischemia and reperfusion injury by oxygen radicals
Fe2+, ferrous iron. Cu+: cuprous ion. COX: cyclooxygenase. NOS: nitric oxide synthase. XO: xanthine oxidase. SOD: superoxide dismutase.
See this image and copyright information in PMC

References

    1. Tsuchiya M, Sako K, Yura S, Yonemasu Y. Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats. Exp Brain Res. 1992;89(1):87–92. - PubMed
    1. Chavez JC, Hurko O, Barone FC, Feuerstein GZ. Pharmacologic interventions for stroke: looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch. Stroke. 2009;40(10):e558–563. - PubMed
    1. Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. J Neurosurg. 1992;77(3):337–354. - PubMed
    1. Friedlander RM. Apoptosis and caspases in neurodegenerative diseases. N Engl J Med. 2003;348(14):1365–1375. - PubMed
    1. Gladstone DJ, Black SE, Hakim AM. Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke. 2002;33(8):2123–2136. - PubMed

Publication types

MeSH terms