| The exact pathologic mechanism of diffuse axonal injury (DAI) is not clear . Until now, there is no effective treatment to DAI. The aims of the present study was to study the pathological characteristic of DAI, to reveal the cause of the memory reduction in DAI by studying injury degree of the hippocampus region, to observe rat's memory and learning behavior after DAI and evaluate the cycolsporin A (CsA) treatment efficacy by using Morris water maze and dark-avoidance test. By studying the expression of P -amyloid precursor protein(3-APP), to reveal the possible treatment mechanism of CsA.Diffuse axonal injury is very common . The morbidity and mortality of DAI remain high. Until now, there is no effective treatment to DAI. The aims of the present study were to study axonal injury characteristic and the injury degree of the hippocampus neuron, to evaluate learning acquisition and memory retention impairments in rats after DAI, to evaluate the CsA treatment efficacy by neurobehavior test apparatus and pathological method, to explore the possible treatment mechanism of CsA.The experimental rats were divided into 4 groups. Group 1 and group 2 was used to study pathological characteristic by hematoxylin and eosin (HE)staining, Bielschowsky staining, immunohistochemistry method and electron microscopy (EM). Group 3 was used to study treatment efficacy of CsA by Behavior analysis. Group 4 was use to study treatment efficacy of CsA by Immunohistochemistry method. The above 4 groups are divided into several subgroups as follows:Groupl (n=32) was divided into 6 subgroups (20 minutes, 2 hours, 8 hours, 24 hours, 7days postinjury groups and control groups). The samples of the rat brain were stained with hematoxylin and eosin (HE) and Bielschowsky stain for histopathology, and with anti?APP for immunohistochemistry. Group 2 (n=21) was divided into 7 groups(20 minutes, 2 hours, 3 hours, 6 hours, 24 hours , 72hours postinjury groups and control groups) for electron microscopy(EM). Group 3(n=24) was divided into 3 subgroups: non-injured group(n=8), vehicle-treated group (n=8)to whom Saline was applied and CsA - treated group(n=8). By analyzing Behavior changes of rats in Morris water maze and dark-avoidance test, the CsA treatment efficacy was evaluated. Group 4 (n=16)was divided into 2 subgroups: vehicle-treated group (n=8) and CsA-treatraent group(n=8). The treatment efficacy was evaluated by quantitative evaluation of P -APP in brain stem and CAS subsector of hippocampus.Results: 1. EM revealed that the loss of microtubules occurred in twenty minutes after injury. In some axonal regions of axon, microtubules even disappeared completely. The loss of microtubules leads to the accumulation of cytoplasm. Expression of {3 -APP was detect in injured rats' brains in two hours after injury and reached peak in twenty-four hours postinjury (F=-45. 10 P<0. 01). Compared classical silver staining methods, immunohistochemistryfor APP is a more sensitive technique. It has been found to be a useful marker for axonal damage. The APP-positive axon was higher in the brain stem. The immunoreactivity in the neuronal perikarya remained high in hippocampus region, and the APP-positive neurons in hippocampus showed shrunken cell body and pyknotic nuclei after injury. 2. The Morris water maze was used to observe rat' memory and learning behavior. During a place-training experiment, the latency to find platform in each trial descended remarkably. Vehicle-treated group exhibited acquisition deficits compared with CsA-treatment group. The latency in each trial was longer in vehicle-treated group ( F=60. 44 P<0. 01). With continued training, the rats' performance in CsA-treatment group was better than those in control brain-injured group in crossing platform test (F=-4, P<0. 01) , but no difference with the normal group. In dark-avoidance test, the rats in normal control group had remembered the electricity shock very fast, and seldom entered into dark chamber. The mean latency time is 292. 88+ 12. 61 seconds. The latenc...
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