Effects Of Mild Hypothermia On The Inflammation Reaction And The Expression Of Nuclear Factor-κB,P-selectin And Intercellular Adhesion Molecule-1 Following Forebrain Ischemia-Reperfusion In Rats

The ischemic brain cell damage is closely related with the inflammation. The migration of the leukocytes, which in the case of cerebral ischemia are mainly neutrophils,and the encephaledema were observed as the mark in the ischemic brain issue. Mild hypothermia was regarded as one of the effective protective methods on cerebral damage following ischemia. But the mechanisms involved in it are still incompletely understood. It was reported that mild hypothermia(33℃) could inhibit the inflammation of the ischemic brain tissue. However,the further studies of the mechanisms were seldom reported.[Objective]To investigate the expression of nuclear Factor-кВ(NF-кВ) , P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the different areas of the brain following forebrain ischemia-reperfusion in rats. And the influence of mild hypothermia on inflammmtion and above indexes were investigated. The necessary experimental evidence will be provided to hypothermic therapy for the treatment of stroke patients. [Methods]Transient forebrain ischemia was induced by bilateral common carotid artery (CCA) occlusion for 9min and blood withdraw to lower the mean arterial blood pressure to 30-35 mmHg, according to the previously described Smith's with some modifications. The live neurons were counted by nissel body stain .Hematoxylin and eosin staining were done for histological analyses, and the activities of myeloperoxidase(MPO) were measured. The expression of NF-кВ, P-selectin and ICAM-1 were measured by immunohistochemical method.[Results]1. The hippocampal CA1 neurons in normothemic group were remarkably absent compared with that in sham-operated group.2. The deformation of the microvascular endothelium and transmigration of the neutrophils were observed at 24 hours,and deteriorated at 48 to 72 hours in normthermic group.3. The activity of MPO increased at 24 hours and peaked at 48 hours in normthermic group.4. All above changes were relieved in the mild hypothermic groups.5. The positive NF-кВ , P-selectin and ICAM-1 immunostaining were markedly enhanced in the normthermic groups,but only slight increased in mild hypothermic groups.[Conclusion]Mild hypothermia has a protective effect on ischemic neurons. There are inflammation after ischemia-reperfusion of the brain. The data presented in this report demonstrated that adhesion molecules are intensely and rapidly induced in rat brain after trainsient forebrain ischemia and reperfusion. It is suggested that adhesion molecules play important roles at the different stages of the inflammation. Mild hypothermia relieved the inflammation reaction by inhibiting the activation of NF-кВ and then decreasing the expressionP-selectin and ICMA-1. It is hypothesized that the inhabition of HF-кВ, P-selectin and ICMA-1 may be one of the mechanism of the neuroprotective effect of mild hypothermia.