Characterization of Inflammatory cells Infiltration in Ischemic Rats

• Main Authors: Chuan-Wei Dong, 董全緯
• Other Authors: Yong-San Huang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/02967315308439617556

碩士 === 國立中興大學 === 獸醫學系暨研究所 === 96 === The principal pathophysiological changes in transient cerebral ischemia are energy failure, ionic and neurotransmitter disturbance, acidosis, excitotoxicity, inflammatory cells infiltration, vascular permeability change, oxidative stress, and programmed cell death. Evidence shows that the delayed neuronal death is attributed to over-activated inflammatory responses including inflammatory cell recruitment, activation, and subsequent production of cytotoxic mediators such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Among the recruited inflammatory cells, resident microglia with an amoeboid macrophage phenotype are activated within the injured areas at the early phase and macrophage migrate from peripheral circulation toward the lesion site at the late phase. Since microglia and marcophage play critical roles in the induction and progression of inflammatory reaction, the present study was aimed to elicit their dynamic changes and potential involvement in post-ischemic brain injury in a stroke animal model. Using focal cerebral ischemia/reperfusion animals, several pathophysiological changes were temporally and spatially detected and analyzed, including neurobehavior, infarction size, histopathology, neuron degeneration, and inflammatory cytokines. In addition, the apparent recruitment of microglia/macrophages as well as resting-to-activated switch were detected in ischemic cortical tissues. For the assessment of immunosuppression, we had focused on both early and late events in the peripheral immune system, sush as leucocytes change in blood, spleen and thymus during ischemia of rat. Our experimental results showed that post-ischemic brain injury was accompanied by weight loss and hypoactivity. Inflammatory factors sush as IL1-β, MMPs, and COX-2 were over-expressed in the injury side. Over-activated microglia (CD45+high/CD11b+high) was observed in the first day and macrophage from peripheral circulation (CD45+med/CD11b+high) was observed in the 5 days after ischemia. The tissue weight of both of spleen and thymus were decreased after ischemia. Because of no obviously change in Treg cells (CD4+/Foxp3+-Treg) in spleen and thymus, there was no evidence indicated the association of immunosuppression and organ atrophy after stroke. Our research was focusing on the development of the experimental focal cerebral ischemia model and evaluation of pathophysiology changes after ischemia. Through the application of these assayed platform and identified critical target molecules, it will help to screen and evaluate poteintially neuroprotective compounds and develop therapeutic strategies for the prevention and treatment of stroke.