title: Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats.
abstract: In traditional Chinese medicine, Ligusticum wallichii Franchat (Chuan Xiong) and its active ingredient tetramethylpyrazine (TMP) have been used to treat cardiovascular diseases and to relieve various neurological symptoms such as ischemic deficits. However, scientific evidence related to their effectiveness or precise modes of neuroprotective action is largely unclear. In the current study, we elicited the neuroprotective mechanisms of TMP after focal cerebral ischemic/reperfusion (I/R) by common carotid arteries and middle cerebral artery occlusion model in rats. TMP was administrated 60 min before occlusion via intraperitoneal injection. TMP concentration-dependently exhibited significant neuroprotective effect against ischemic deficits by reduction of behavioral disturbance. Neuronal loss and brain infarction in the ischemic side of rats were markedly lowered by treatment with TMP. Cerebral I/R-induced internucleosomal DNA fragmentation, caspase-8, caspase-9, and caspase-3 activation, and cytochrome c release were reduced by TMP treatment. Western blot analysis revealed the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax and Bad by cerebral I/R insult. Among them, only the alteration in Bcl-xL expression was reversed by TMP treatment. Moreover, the activation of microglia and/or recruitment of inflammatory cells within the ischemic side and the consequent production of monocyte chemoattractant protein 1 (MCP-1) were suppressed by TMP pre-treatment. Our findings suggest that TMP might provide neuroprotection against ischemic brain injury, in part, through suppression of inflammatory reaction, reduction of neuronal apoptosis, and prevention of neuronal loss.
authors.affiliation: Department of Nursing, Tajen Institute of Technology, Pingtung, Taiwan.
authors.forename: Tsung-Kuei
authors.initials: TK
authors.lastname: Kao
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Ou
authors.forename: Jong-Song
authors.initials: JS
authors.lastname: Kuo
authors.forename: Wen-Yin
authors.initials: WY
authors.lastname: Chen
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Liao
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Nai-Nu
authors.initials: NN
authors.lastname: Ling
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Wen-Huang
authors.initials: WH
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D011719:Pyrazines; C017953:tetramethylpyrazine