Spatio-temporal distribution of inflammatory reaction and expression of TLR2/4 signaling pathway in rat brain following permanent focal cerebral ischemia.
Toll-like receptors (TLRs) are considered to mediate the inflammatory reaction, which are involved in the pathophysiological processes of cerebral ischemia injury. To elucidate the possible role of inflammatory reaction and TLR2/4 signaling pathway in cerebral ischemia, in the present study, we explored the spatio-temporal distribution of inflammatory reaction, and further investigated the time-course expression of TLR2/4 and the downstream effector molecules after focal cerebral ischemia in rats. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO) for 6, 12, 24, 48 and 72 h. Neurological deficit, cerebral infarction and neutrophil infiltration were measured at different time points following pMCAO. Expression of TLR2/4 were examined by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) were determined by western blot. Serum content of tumor necrosis factor-alpha (TNF-alpha) was detected by enzyme-linked immunosorbent assay (ELISA). Experimental results showed that pMCAO caused an increase of neutrophil infiltration in infarcted brain tissue, with a peaked activity at 24 h of ischemia. The inflammatory molecules including TLR2, TLR4, NF-kappaB, COX-2 and TNF-alpha were significantly increased after pMCAO, especially during 12-24 h of ischemia, which were correlated with pMCAO-induced brain injury and cerebral inflammation. Our studies suggested that TLR2/4 signaling pathway likely aggravated ischemic brain injury through mediating the inflammatory reaction. TLR2/4 signaling pathway may be a promising therapeutic target for cerebral ischemia injury.
Tu
Xian-kun
XK
Department of Neurosurgery, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Yang
Wei-zhong
WZ
Shi
Song-sheng
SS
Wang
Chun-hua
CH
Zhang
Guo-liang
GL
Ni
Tian-rui
TR
Chen
Chun-mei
CM
Wang
Rui
R
Jia
Jian-wen
JW
Song
Qi-min
QM
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000276:immunology / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000276:immunology; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase
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