title: Neuroprotective effect of asiatic acid in rat model of focal embolic stroke.
abstract: Asiatic acid (AA) is a pleiotropic neuroprotective agent that has been shown to attenuate infarct volume in mouse and rat models of focal ischemia and has a long clinically relevant therapeutic time-window. Because in a future trial AA would be administered with tissue-plasminogen activator (t-PA), the only approved acute stroke therapy, we sought to determine the effect of AA when co-administered with t-PA in a rat focal embolic stroke model. Male rats were treated with AA (75 mg/kg) alone, low-dose t-PA (2.5 mg/kg) alone, or a combination of AA and low-dose t-PA at 3 h after inducing embolic stroke. AA significantly reduced infarct volume whereas low-dose t-PA alone did not reduce infarct volume compared with vehicle. Significantly, combination treatment further enhanced reduction of infarct volume versus AA alone. Treatment with AA reduced cytochrome c (CytoC) and apoptosis-inducing factor (AIF) release from brain mitochondria after ischemia. AA was also neuroprotective against L-glutamate-induced toxicity in primary cortical neurons. In summary, combination treatment with AA and low-dose t-PA at 3 h after embolic stroke reduces infarct volume, improves neurological outcome, and provides neuroprotection. The neuroprotective effects of AA were partially associated with reduction of AIF and CytoC release.
authors.affiliation: Division of Cerebrovascular Diseases and Department of Neurology and Ophthalmology, Michigan State University.
authors.forename: Ki Yong
authors.initials: KY
authors.lastname: Lee
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Shelley
authors.initials: S
authors.lastname: Weinstock
authors.forename: Mounzer
authors.initials: M
authors.lastname: Kassab
authors.forename: Arshad
authors.initials: A
authors.lastname: Majid
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D045304:Cytochromes c; C017032:asiatic acid