title: Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats.
abstract: Tetramethylpyrazine (TMP) has been used to treat ischemic stroke. However, scientific evidence related to its effectiveness or precise modes of neuroprotective action is largely unclear. This study provides evidence of an alternative target for TMP and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of TMP on intracerebral cellular inflammatory response in a rat model of permanent cerebral ischemia. TMP exhibited a neuroprotective effect against ischemic deficits by reduction of behavioral disturbance, brain infarction, and edema. The results of immunohistochemistry, enzymatic assay, Western blot, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and flow cytometric analysis revealed that TMP reduced the percentages of activated macrophages/microglia and infiltrative lymphocytes, neutrophils, and macrophages and pro-inflammatory cytokine expression after cerebral ischemia. In parallel with these immunosuppressive phenomena, TMP also attenuated the activities of ischemia-induced inflammation-associated signaling molecules and transcription factors. Another finding in this study was that the anti-inflammatory and neuroprotective effects of TMP were accompanied by a further elevated expression of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in ipsilateral neurons and macrophages/microglia after cerebral ischemia. Taken together, our results suggest that both the promotion of endogenous defense capacity and the attenuation of the extent and composition percentage of the major cellular inflammatory responses via targeting of macrophages/microglia by elevating Nrf2/HO-1 expression might actively contribute to TMP-mediated neuroprotection against cerebral ischemia.
authors: School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, China.
authors: Tsung-Kuei
authors: TK
authors: Kao
authors: Cheng-Yi
authors: CY
authors: Chang
authors: Yen-Chuan
authors: YC
authors: Ou
authors: Wen-Ying
authors: WY
authors: Chen
authors: Yu-Hsiang
authors: YH
authors: Kuan
authors: Hung-Chuan
authors: HC
authors: Pan
authors: Su-Lan
authors: SL
authors: Liao
authors: Guo-Zhang
authors: GZ
authors: Li
authors: Chun-Jung
authors: CJ
authors: Chen
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy; D039481:CD11b Antigen / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D004660:Encephalitis / Q000209:etiology* / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D005343:Fibrinolytic Agents; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; C495637:Nfe2l2 protein, rat; D011719:Pyrazines; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D017493:Leukocyte Common Antigens; C017953:tetramethylpyrazine
keywords: Leukocyte; Neuroinflammation; Stroke; Tetramethylpyrazine