Exercise Training exert Neuron Plasticity andAcute Proinflammation Cytokine Regulation viaHeat Shock Protein 70 Overexpression inTraumatic Brain Injury

• Main Authors: Yu-Chien Chen, 陳宥婕
• Other Authors: 張菁萍
• Format: Others
• Language: zh-TW
• Published: 103
• Online Access: http://ndltd.ncl.edu.tw/handle/asuuzc

碩士 === 南台科技大學 === 生物科技系 === 102 === Background: A promising treatment strategy is that of preconditioning. Preconditioning is the notion that a subtoxic stimulus is applied to a tissue in curring a response in that tissue that then protects it from, or limits the damage when a similar, or even worse, an otherwise lethal stimulus would followed. For example, exercise preconditioning increases heat shock protein (HSP) 70expression, and the presence of HSP70 before a stroke attenuates neuronal injury in rats. However, the effect of treadmill exercise on TBI- induced cognitive and motor function loss in relation to neuroinflammation, neural plasticity defects, apoptotic neuronal cell death, and neurodegeneration remains unclear. Aim: In this study, we were used the rat TBI model to investigate: (1) How treadmill running exercise precondition affect molecular events (e.g. inflammation or death signals) caused by TBI in rats; (2) How the treadmill running exercise precondition affects the expression of synapsin I correlates of synaptic plasticity in TBI rats; and (3) Whether treadmill running exercise improve cognitive and motor functions via stimulating synaptic plasticity following TBI. Materials and Methods: Rats will be underwent surgery to induce either sham operation injury (Sham) or TBI injury followed by hsp70gene knockdown (shhsp70, 50g/kg, i.c.v.) or vector (vector, 50 g/kg, i.c.v.) treatment. Rats will be trained with treadmill exercise (Exercise) or under sedentary (Sedentary) conditions for 21 days before or after TBI, thus resulting in the following groups: The rats were randomly assigned to one of six groups: (1) Sham operation without exercise preconditioning vii (Sham/Sedentary); (2)Sham operation with exercise preconditioning (Sham/Exercise); (3) Sham operation with exercise preconditioning and short hairpin heat shock protein 70 (shHSP70) injection (Sham/Exercise+shHSP70); (4) TBI without exercise preconditioning (TBI/Sedentary); (5) TBI with exercise preconditioning (TBI/Exercise); (6) TBI with exercise preconditioning and shHSP70 injection (TBI/Exercise+shHSP70). To deal with the question, the present study will attempt to assess acute changes in several physiological and pathological parameters (including blood pressure, cell morphology, BBB permeability, infarction area measurement), brain HSP 70 expression (exercise marker), synapsin-1 (neuroplasticity marker), serum profiles of all cytokines and chemokines, and neuroinflammatory cytokines after TBI. Results: In a fluid-percussion injury model of TBI, exercised rats had significantly higher levels of HSP70 in different brain regions, a lower functional deficit, fewer cerebral contusions, and fewer apoptotic cells than did non-exercised rats. shHSP70 was injected into the contused cerebral cortex. In addition to reducing HSP70, the shHSP70 significantly attenuated the beneficial effects of exercise preconditioning in reducing cerebral contusion and apoptosis. Cytokines and chemokines analysis were used by RT-PCR method. Cytokines serve a central function as key factors in the regulation of the immune response and mediation of tissue damage, especially in interleukin-6 (IL-6). And IL-6 expression was dependent on NF-κB activity. Exercise preconditioning promoted functional recovery in rats after TBI by upregulating HSP72 in the contused cortex of the injured brain. Conclusion: As mentioned above, chronic physical (exercise) conditions can induce over-expression of HSP-70. The fairly high level of HSP-70 prior to viii ischemia/reperfusion injury was essential in reducing brain infarction and apoptosis in exercised rats after TBI. This indicates that effects of HSP-70 on neuroprotection occur at pre-ischemic episodes. Although exercise and TBI both induced HSP-70 expression, only pre-ischemic expression seemed to confer neuroprotection. In addition, inhibition of HSP-70 completely diminished exercise induced neuroprotection, suggesting that certain levels of HSP-70 are essential in exercise-associated neuroprotection. We reveal an important function of brain HSP70 in protecting neuronal apoptosis in the injured cortex. We conclude that exercise preconditioning is a promising treatment strategy for facilitating functional recovery from TBI in rats.