| Summary: | 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,
50g/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
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(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
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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.
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