| Diffuse brain injury(DBI), a type of closed head injury, is associated with high mortality and morbidity. Studies by the Traumatic Coma Data Bank study group showed that 55% of patients comatose on admission suffer from diffuse brain injury. Current understanding of the pathophysiology of DBI stresses the importance not only of the primary injury, but also the secondary processes occurring after injury which may lead to cerebral hypoxia and ischemia called secondary brain insults(SBI) . Patients with SBI normally had increased mortality and morbidity in comparison with DBI alone. Approximately 2/3 patients with severe brain injuries suffered from hypoxia and hypotension during prehospital, and even on addmission, there is still 1/3 patients suffering from hypoxia and hypotension according to the Guidelines for the Management of Severe Head Injury in USA. With the progress in researching on DBI, more and more patients with DBI were detected in clinical work. However, because the DBI with SBI is not situated for operation, many neuroprotective agents were designed according to its secondary processes. Metabotropic glutamate receptor (mGluR), as one of the newly-detected glutamate receptors, is classified into three main groups on the basis of sequence homology, coupling to second messenger systems, and selectivity for various agonists. Activation of group IImGluRs may provide neuroprotective effect, which brings new sight for the therapy on DBI with/without SBI. In this study, the SBI model was created by bilateral carotid occlusion for 30 minutes on the basis of Marmarou's DBI model. Then the changes of group II mGluRs mRNA were dectected by in-situ hybridization and the neuroprotective effects of group II mGluRs specific agonists DCG-IV were also studied.?? Establishment of the SBI model:Aim: On the basis of Mamarou DBI model , SBI was produced by occlusing arteriae carotis communis. Material and methods: SD rats were randomized into four groups: normal control, sham-operated, DBI alone and DBI with SBI group. DBI was produced by acceleration-deceleration model of traumatic brain injury developed by Marmarou, et al. Fifteen minutes following the impact injury, a secondary insult was produced by bilateral carotid occlusion for 30 minutes. Then the rats were tested for the motor and cognitive performance(NSS) 12 hours after injuries. The water contents and the numbers of injured neurons were counted at different intervals post-injuries. Results: The rats of normal control and sham-operated group all survived. Their NSS water contents and neurons are normal.The mortality of DBI coupled with SBI was apparently higher than that of DBI alone(25.7% v.s. 14.3%, P<0.05). The NSS of DBI coupled with SBI rats is much higher than that of DBI alone 12 hours after injury(P<0.05). The water contents of DBI coupled with SBI rats was much higher than that of DBI alone at any time-point after injury except 1 hour after injury (.P<0.05 ). The peak value was at 12 hours after injury and the content was still significantly high 72h after injury. Damaged neurons number increased significantly 12 hours after DBI with/without SBI(P<0.05), and did not return tonormal level at 72h after injury. Conclusion: This model can produce the SBI process similar to the clinical characteristics and can be used to study the pathophysiological process of DBI coupled with SBI in the future. ??Study of transcription of group IlmGluRs of DBI alone and DBI coupledwith SBI.Aim:On the basis of the animal model stated above, the changes of group IlmGluRs after DBI coupled with SBI in rats were studied. Material and methods: The mRNA of the mGluRs were detected in Ih, 3h, 6h, 12h, 24h, 48h, 72h after injuries by in-situ hybridization. To assess the expression quantitatively, numbers of positive neurons per high-power microscope field(400X) were counted manually in the supraventricular cerebral cortex. Results: signals of hybridization are brown principally situated at plasmolysis. The expression of mGluR2,3mRNA in the supr...
|
PDF Full Text Request