| 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 in USA showed that 55% of patients comatose on admission suffered from DBI. 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) which are associated with increased mortality and morbidity in comparison with DBI alone. Approximately 2/3 patients with severe brain injuries suffered from hypoxia and hypotension during pre-hospital, and even on admission, there is still 1/3 patient with hypoxia and hypotension according to the Guidelines for the Management of Severe Head Injury in USA. The DBI with SBI is not suitable for operation, so many neuroprotective agents were designed according to the secondary processes. But to date, none of the neuroprotective agents showed efficacy in the general population of patients with severe brain injury according to the recent report on the results of trials of neuroprotective agents in brain injury. Metabotropic glutamate receptor (mGluR), as one of the newly-found glutamate receptors, are classified into three main groups on the basis of sequence homology, coupling to second messenger systems, and selectivity for various agonists. Activation of group III mGluRs can provide neuroprotective effects, which brings new sight for the therapy of DBI with/without SBI. In this study, the SBI model was created by bilateral carotid occlusion on the basis of Marmarou's DBI model. Then the changes of group HI mGluRs mRNA were detected by in-situ hybridization and the neuroprotective effects of group HI mGluRs specific agonists L-AP4 were also studied. 1. The experimental study on the animal model of DBI with SBIObjective To set up a new model to study the pathophysiology of DBI with SBI in rats.Methods 175 male SD rats were randomized into five groups: normal control, sham-operated, cerebral ischemia alone, DBI alone and DBI with SBI group. DBI was produced by acceleration-deceleration model of traumatic brain injury developed by Marmarou et al. 15 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 12 hours after injuries. The water contents and the numbers of injured neurons were recorded at different intervals post-injuries. Results The morality of DBI with SBI was double as much as that of DBI alone CPO.05). The NSS of rats with DBI with SBI was much higher than that of DBI alone 12 hours after injury (/><0.05). The water contents of rats with DBI with SBI were 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 contents were still significantly high 7days after injury (PO.05); The evolution of neuronal damage in the DBI alone was relatively static at 12 hours, however, there was a remarkable increase in the neuronal damage of the DBI with SBI group. The damaged neurons of DBI with SBI reached the peak 24-72 hours after injury when the damaged neurons of the DBI with SBI group were much more than that of the DBI group (PO.05). Conclusion The mortality of rats with DBI is increased, and the traumatic brain edema and neuronal damage exacerbated after it coupled with SBI.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. 2. The changes of group in mGluRs in the cerebral cortex of rats with DBI and SBI.Objective To study the changes of group HI mGluRs in the cerebral cortex of rats with DBI and SBI. Methods On the basis of the DBI and SBI models stated above, the mRNAs of the mGluRs were detected in Ih, 6h, 12h, 24h, 72h, and I68h after injuries by in-situ hybridization. To assess the expression qu...
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