|M.Sc Student||Tachlykov Vadim|
|Subject||Behavioral and Morpho-physiological Properties after|
Minimal Brain Injury
|Department||Department of Medicine||Supervisors||Professor Yeshayahu(Sha Katz|
|Professor Chaim Pick|
|Full Thesis text|
The interpretation of cellular and molecular pathogenetic basis of post-traumatic brain pathology is an important clinical and scientific problem because of the wide distribution of this pathology and a high percentage of disability. Because of great clinical importance of the problem and the necessity to optimize therapeutical approaches to such patients, the majority of studies pay attention to severe and moderate brain trauma. Based on clinical and experimental data, it has recently become understood that even mild traumatic brain injury (TBI) can cause many psychiatric and neurologic problems. With the aim of gaining deeper knowledge of the changes in different brain structures after minimal trauma we used a weight-drop experimental model on mice. Different weights: 5, 10, 15, 20, 25 and 30 g, were dropped from a height of 80 cm on the right side of the mice's head under ether anesthesia. Behavioral analysis using the staircase test showed minimal changes at 1h after TBI, which were resolved at 72h after traumatic impact. At 72h posttrauma all used histological methods showed significant appearance of diffuse neurodegenerative process in all analyzed cortical and hippocampal areas. At the same time it was accompanied by a decrease in the total number of neurons in those regions. Anterior cingulate and frontal cortices and CA3 hippocampal regions showed the most widespread neurodegeneration. This neurodegeneration included different cellular states, both necrosis and apoptosis. The quantity of TUNEL-positive cells increased in a non-linear fashion with the degree of trauma. It was accompanied with an increase of downstream caspase immunoreactivity of total brain homogenate. Our data show an elevation of the amount of p53 or c-Jun proteins in the total brain. Regional distribution of p53 and c-Jun-labeled cells conformed to the distribution of degenerated neurons. In addition to the apoptotic appearance we observed activation of antiapoptotic mechanisms. Western blot analysis showed elevation of bcl-2 immunoreactivity of total brain homogenate after traumatic impact. No statistically clear differences in expression of diffuse neurodegeneration were observed between the hemispheres. Trauma by 15g weight was the threshold to activation of neurodegeneration. We did not find any changes in the level of synaptospecific proteins in total brain homogenates, such as synapsin I and synapsin II.
Balance in activation of different necrotic, pro-apoptotic and anti-apoptotic intracellular and extracellular events can be the central responsible factor of the development of post-traumatic neurodegeneration.