| Craniocerebral injury is ranked no.1in trauma, with relatively high mortality and morbidity. Diffuse brain injury is one kind of craniocerebral injury, the treatment is very difficult, the mortality is more than60%, the rehabilitation is bad.Diffuse brain injury can cause primary brain injury(brain nerve tissue and brain blood vessel injury caused by mechanical injury factors) and secondary brain injury(Cerebral ischemia, brain edema, intracranial hematoma, cerebral edema,increased intracranial pressure caused by tissue reaction, physiological changes, blooding and other factors after primary brain injury. Therefore, if timely diagnosis and effective treatment of diffuse brain injury are not carried out, it can lead to the occurrence of progressive intracranial hypertension, pathological changes of primary brain injury, as well as herniation, central failure and even death.In recent years, a variety of treatment methods, including operation and on operation treatment were carried out according to pathological and physiological changes of brain injury, the development of CT, MRI and other neuroimaging techniques make the diagnosis of craniocerebral injury reach a high level, mortality of some craniocerebral injuries(such as intracranial hematoma) has obviously declined. But no breakthrough has been made in treatment methods of diffuse brain injury, the mortality remains high.There is no effective method for treatment of diffuse brain injury, treatment of cerebral edema, reduction of intracranial pressure and prevention of secondary damage are the main existing methods. The understanding of pathological mechanism of diffuse brain injury can only be realized through clinical symptom, imaging examination, autopsy and other means, therefore, the establishment of diffuse brain injury model for animals that is similar to human and the study on nosogenesis of diffuse brain injury draw increasingly more attention. Part I The model of diffuse brain injury in rats and the expression of c-fos and c-junObjective To study the expression pattern of c-Fos and c-Jun in the cerebral cortex of Adult male Sprague-Dawley rats with diffuse brain injury (DBI) and investigate their potential roles in DBI treatment.Methods Adult male SD rats were anesthetized and subjected to TBI by a weight drop onto the exposed right parietal cortex. At30min,1h,3h,6h,12h,1d,3d,7d after TBI, traumatized brain tissues were prepared for pathological, immunohistochemical analysis, including HE staining, ultrathin sections electron microscopy, brain water content analysis and transcript analysis.Results The water content of injured brain tissuses increased1hour post-injury, peaked24hours post-injury, then decreased. Histological examination of H&E stained sections showed vacuolations around neurons in all injured rats at all sacrifice time points. There were also small spots of bleeding in the cortex and corpus callosum and several capillaries also were seen to be congested. Immunochemical staining of rat brain sections shows APP accumulation in the brain stem, hippocampus, thalamus, corpus callosum and the periventrical areas at24h after injury as compared to sham treated rats. Electron micrographs showed at3d after injury, advanced stages of axonal damage were characterized by myelin thinning and marked edema. At1hour after brain injury, a significant increase in c-Fos and c-Jun postive cells were obsered. The expression level of c-Fos peaked at3h,then decreased lately, and the second peak time was the3d after brain injury. The c-fun peaked at6h and3d,which was followed by a gradual decline and7d was the lowest, but still higher than that in the control group.Conclusion1After diffuse brain injury, water content of rat brain tissues increase, c-Fos, c-Jun in nerve cells show high expressions.2After diffuse brain injury, there is a certain correlation between brain tissue edema and c-Fos, c-Jun expressions, different variations occur over time. Part Ⅱ:The protection of hypothermia in rats with diffuse brain injury and the related mechanismObjective To examine the effect of hypothermia (HT) on SD rats with diffuse brain injury (DBI) and investigate their potential roles in DBI treatment.Methods Adult male Sprague-Dawley rats were randomly divided into sham operation, DBI1d group and DBI1d+HT (30℃) group. Rats were anesthetized, intubated, mechanically ventilated, and subjected to TBI by a weight drop (450g×150cm) onto the exposed right parietal cortex. Hypothermic rats were then cooled to a brain temperature of30℃for6h, and control rats were maintained at a brain temperature of37℃. Rat brains at1day after injury, were collected to determine histopathological damage and the expression levels of c-fos, c-jun.1day after insult, animals were challenged with Morris water maze test and brain water content, brain edema were investigated.Results Compared the DBI group, the survival rate of rats in HT (30℃) treated group was greatly improved, the infarct volume, cerebral ischaemia and brain edema was significantly reduced, the average time of escape latency was significantly shorter and the number of platform location crossing was more. HE staining displayed that the pathological injuries in the hippocampus were alleviated in the HT-treated DBI group when compared with the untreated DBI group. The HT-treated control group showed increased survived neurons compared with the untreated DBI group. The expressions of c-fos, c-jun were reduced in HT treated groups compared to those in DBI group.Conclusion These findings indicate that the HT treatment can enhance the neuroprotective effect in the DBI model partially mediated by inhibiting c-fos, c-jun pathways. Part Ⅲ Theprotection and mechanism of hyperbaric oxygen therapy in rats with diffuse brain injuryObjective To evaluate the effect of hyperbaric oxygen (HBO) on SD rats with diffuse brain injury (DBI) and investigate their potential roles in DBI treatment.Methods Adult male Sprague-Dawley rats were randomly divided into sham operation, DBI3d group and DBI3d+HBO group. Rats were anesthetized and subjected to TBI by a weight drop (450g×1.5m) onto the exposed right parietal cortex. DBI3d+HBO group was treated for2h at2.5absolute atmosphere (ATA) per day for3days. Rat brains at3days after DBI, were collected to determine histopathological damage and the expression levels of c-fos, c-jun, Bax and Bcl-2.3days after insult, animals were challenged with Morris water maze test and brain water content, brain edema were investigated.Results Compared the DBI group, the survival rate of rats in HBO treated group was greatly improved, the infarct volume, cerebral ischaemia and brain edema was significantly reduced, the average time of escape latency was significantly shorter and the number of platform location crossing was more. HE staining displayed that the pathological injuries in the hippocampus were alleviated in the HBO-treated group when compared with the untreated DBI group. The HBO-treated contrfol group showed increased survived neurons compared with the untreated DBI group. The expressions of c-fos, c-jun, caspase-3, bax were reduced in HBO treated groups compared to those in DBI group.Conclusion These findings indicate that the HBO treatment can enhance the neuroprotective effect in the DBI model partially mediated by inhibiting c-fos, c-jun and bax pathways. |
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