ABSTRACT
AIM:To investigate the regulatory effect of JAK 2-STAT3 signaling pathway on the neuroprotection of ischemic postconditioning (IPoC) in tree shrews, and to explore the mechanisms of cerebral injury deterioration after in-hibiting the JAK2-STAT3 pathway .METHODS:The model of thrombotic cerebral ischemia was induced by photochemical reaction in tree shrews and the IPoC was established at 4 h after ischemia followed by clipping ipsilateral common carotid ar-tery on the ischemia side for 5 min ( 3 times ) .After IPoC and intracerebroventricular injection of AG 490 ( JAK2 inhibi-tor), the changes of cerebral infarction area were detected by TTC staining , and the histological and ultrastructural changes of cortical neurons were observed under light and electron microscopes , respectively .The protein levels of t-STAT3 and p-STAT3 in the cortical tissue were determined by Western blot .RESULTS:The neuronal pycnosis , mitochondrial swelling and vanish of the mitochondrial cristae were found in cortical cortex , and the infarction area was (24.78 ±3.30)%at 24 h after cerebral ischemia .Meanwhile, the phosphorylation level of STAT 3 protein in the cortical tissue was significantly in-creased (P<0.01).The cortical neuronal damage and mitochondrial swelling were decreased after IPoC , the area of cere-bral infarction was significantly reduced to (17.67 ±1.83)%(P<0.01), and the phosphorylation level of STAT3 protein was further increased ( P<0.01 ) .However , the neuronal damage was aggravated , the infarction area was expanded to (23.85 ±2.77)%(P<0.05) after treatment with AG490, and the phosphorylation level of STAT3 protein was also signif-icantly reduced ( P <0.05 ) .CONCLUSION: IPoC may reduce cerebral injury by regulating the phosphorylation of STAT3 protein, and inhibition of JAK2-STAT3 signaling pathway may counteract the cerebral protective effect of IPoC and aggravate brain injury .
ABSTRACT
AIM:To assess whether the expression of tight junction (TJ) proteins, occludin/zonula occludins (ZO)-1, and regional cerebral blood flow (rCBF) link to brain edema in tree shrews during thrombotic cerebral ischemia and ischemic postconditioning (PC), and to explore how TJ affects brain edema and cerebral infarction .METHODS:Tree shrews were randomly grouped into control , ischemia and cerebral ischemia +PC (n=23), and the remaining 3 ani-mals were used for magnetic resonance imaging ( MRI) .The local cerebral thrombosis were induced by photochemical reac-tion in the tree shrews , and ischemic PC was established at 4 h after induction of cerebral ischemia followed by clipped ipsi-lateral common carotid artery (5 min ×3).The changes of the neural ultrastructure were observed under electron micro-scope.The neuronal apoptosis was analyzed by the method of TUNEL .Laser Doppler brain flowmetry was used to monitor the rCBF.The protein levels of occludin/ZO-1 were determined by immunochemistry and Western blot .The cerebral in-farction volume was detected by MRI .The brain water content was measured by dry-wet weight method .RESULTS: In-duction of cerebral ischemia led to a significant reduction of the normal neuron numbers in the hippocampal CA 1 area, and conversely, the number of neurons with abnormal ultrastructure was increased .The TUNEL positive cells were increased significantly (P<0.01) in ischemia group.Moreover, the rCBF decreased significantly (P<0.01), and occludin/ZO-1 protein expression decreased ( P<0.01 ) .The brain water content and cerebral infarction volume were significantly in-creased (P<0.01).Ischemic PC increased the rCBF and the occludin/ZO-1 expression, but reduced the brain water con-tent, the TUNEL positive cells, and the infarction volume (P<0.01).CONCLUSION:Ischemic PC increases the rCBF but not the local water content , suggesting that reduced cerebral infarction volume after ischemia PC is associated with the attenuation of cerebral edema by the enhancement of occludin /ZO-1 protein expression .