title: Central nervous system agents for ischemic stroke: neuroprotection mechanisms.
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.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Department of Neurosurgery, Boston, Massachusetts 02115, USA.
authors.forename: Rachna S
authors.initials: RS
authors.lastname: Pandya
authors.forename: Lijuan
authors.initials: L
authors.lastname: Mao
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Zhou
authors.forename: Jiang
authors.initials: J
authors.lastname: Zeng
authors.forename: A John
authors.initials: AJ
authors.lastname: Popp
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018836:Inflammation Mediators / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D002491:Central Nervous System Agents; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D018696:Neuroprotective Agents