C-fos Gene Expression And Changes Of Beta-endorphin After Secondary Brain Insults

Secondary brain insult(SBI)followed traumatic brain injury (TBI) is a mainfactor that influences the outcome. In this study, the SBI model was created bybilateral carotid occlusion on the basis of Marmarou's diffuse brain injury(DBI) model.Then the changes of c-fos gene expression in brain and beta-endorphin of bloodplasma were detected. The neuroprotective effects of naloxone hydrochloride werealso studied. The research consists of three parts:1.The changes of c-fos gene expression in brain and beta-endorphin of bloodplasma of rats with DBI and SBIMethods : Total of 163 male SD rats were divided into five groups randomly:normal control, sham-operated, cerebral ischemia alone, DBI alone and DBI with SBIgroup. DBI was produced by acceleration-deceleration model of traumatic braininjury developed by Marmarou et al. 15minutes following the impact injury, asecondary insult was produced by bilateral carotid occlusion for 30 minutes. Then thec-fos protein in brain were detected by immunohistochemistry and beta-endorphin ofblood plasma were detected by radioimmunoassay. The water contents and thepatho-microstructure of brain were also observed. Results: The c-fos gene expressionafter DBI with SBI in neuron has two peaks, one peaking at three hours, anotherexpression peak appeared 24 hours later. The numbers of c-fos-positive cell in DBIwith SBI group was much higher than that of cerebral ischemia alone and DBI aloneat any time-point after injury except one hour after injury (P<0.05). Thebeta-endorphin of blood plasma in DBI with SBI group peak value was at one hoursafter injury and the contents were still significantly high 48 hours after injury(P<0.05). The beta-endorphin of blood plasma in the DBI with SBI group were muchhigher than that of cerebral ischemia alone and DBI alone at any time-point afterinjury(P<0.05). The water contents of rats with DBI and SBI were much higher thanthat of cerebral ischemia alone and DBI alone at any time-point after injury, exceptfor one hour after injury (P <0.05). The numbers of neuronal damage of rats with DBIwith SBI were much higher than that of cerebral ischemia alone and DBI alone from 6hours after injury (P <0.05). Conclusion:The increasing of c-fos gene expression andbeta-endorphin may contribute to the pathobiologic changes after DBI with SBI. Theresults of experiment indicate that the alteration of c-fos gene expression andbeta-endorphin may correlate to the development of SBI. 2.The effect of naloxone hydrochloride on c-fos gene expression in brain andbeta-endorphin of blood plasma of rats with DBI and SBI Methods:All animals in treatment group were injected intraperitoneal withnaloxone hydrochloride(3.0mg/kg) 15 minutes after injuries or 15 minute beforeinjuries, while all animals in control group were injected with 0.9% saline instead.Then the rats were tested for the motor and cognitive performance 24 hours afterinjuries. The water contents, the numbers of injured neurons were recorded, thebeta-endorphin of blood plasma and the number of c-fos-positive cell were recordedat different intervals post-injuries. Results: The morality, the water contents in thefrontal cortex , the beta-endorphin of blood plasma , the numbers of c-fos-positive celland the damaged neurons of treatmental group were lower than that of control group(P<0.05). Conclusion:The results of this study indicate that naloxone hydrochlorideprovides remarkable protection against the damage exacerbated by secondary insults. 3.The risk factor of secondary brain insults effects on the beta-endorphin ofblood plasma and outcome of patient with acte severe craniocerebral injury Methods: 48 patients with acte severe craniocerebral injury were divided into 2groups according to suffering form the risk factors of SBI or not. The beta-endorphinof blood plasma and the GOS were compared between the two groups. Results: Thebeta-endorphin of blood plasma of patients suffered form risk factor of SBI werehigher than that of the without risk factors of SBI at six days after hospital admission(P<0.05). When patients discharged , the GOS of the patients who were suffered formrisk factor of SBI were lower than that of the patients who were not suffered form riskfactor of SBI (P <0.05). The beta-endorphin of blood plasma of patient was inversecorrelation to the GOS of patient (P <0.05). Conclusion: The outcome of patient withacte severe craniocerebral injury was aggravated by the risk factor of SBI. Theincreasing of beta-endorphin may correlate to the development of SBI and is asignificance factor which effect on the outcome of patient with acte severecraniocerebral injury.