| Traumatic brain injury (TBI) is the chief cause of death in the people younger than 45 years. Diffuse brain injury (DBI) is associated with high mortality and morbidity. Studies by the Traumatic Coma Data study group in USA shows that 55% of patients comatose on admission suffered from DBI. The DBI is not suitable for operation; so many neuroprotective agents were designed according to this process. According to our study, the mGluRs are closely involved in the pathology of DBI. Accumulation of glutamic acid in brain after traumatic injury is due to various acute or chronic pathological insults on neurons. Change of metabotrobic glutamate receptor la (mGluRla) is the most prominent in the families of mGluRs after diffuse brain injury and plays an important role in aggravating neuronal damages. It was found that the mGluR I had the agonist-independent activity, inwhich they could mediate the increases of IP3 and the opening of Ca2+-dependent K+ channel in cell without agonist, and the agonist-independent activity was found to be mediated by new signal transduction molecules - Homer.In our experiments the change of Homer molecules, which interacts with mGluRla after neuron injury, will be studied and the key Homer molecules will be selected on the basis of Marmarou rat DBI model hoping to provide a new insight for the development of neuroprotective agents.1.The establishment of the DBI animal modelObjective To set up a DBI animal model in rats. Methods one hundred and five(105) male SD rats were randomized into three groups: normal, sham- operated and DBI group. DBI was produced by acceletation -deceletation model of DBI by Marmarou et al. Then the rats were tested for the motor and cognitive performance 12 hours after injury and the numbers of injured neurons were recorded at different intervals post-injuries. Results The NSS of rats with DBI was much higher than that of the other groups (P<0.05=;there was a remarkable increase in the number of damaged neurons in the DBI group 30minin after injury and the increase remained significantly 7 days after injury(P<0.05).Conclusion The successful establishment of this model can provide solid foundation for the following study.2.The study on the expression and significance of Homer in rats after DBI by the immunohistochemistry way.Objective To study the expression time and significance ofHomer in rats after DBI and select the key Homer molecules, which interacts with mGluRla preparatorily. Methods One hundred and five SD rats were randomized to normal group, sham-operated group and DBI group. The Marmarrou rats DBI models were used to result in DBI in DBI group, the sham-operated group was treated as DBI group except for "free fall" attack. The rats' main brain areas and nuclei, for example: nervous tissue of frontal lobe and parietal lobe, were sampled to detect for Homer1 by immunohistochemistry after injury at 30min, 1, 6, 12, 24, 72 and 168h respectively. Results There was no expression of Homer la on neurons in the normal and sham-operated group, but evident expression was found in DBI group and the positive stain were present in nerve cell membrane, cytoplast and process after injury from 30min to 168h ; Homer1b/c, Homer2a/b and Homer3 were present in normal group, sham-operated group and DBI group. Conclusion Dynamically expressed Homer la and constitutively expressed Homer1b/c, Homer2a/b and Homer3 might further modulate the distribution and function of mGluRla, and Homerla is closely involved in neuron injury.3. The study on the expression and significance of Homer in rats after DBI by the immunoblotting way.Objective To study the expression and significance of Homer in rats after DBI more and verify the key Homer molecules that interacts with mGluRla. Methods One hundred and five SD rats were randomized to normal, sham-operated and DBI group. The Marmarrou rats DBI models were used to result in DBI in DBI group, and the...
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