Differential Expression Of NGF, Bcl-2 And Bax Gene In Aged And Young Rats After Fluid Percussion Brain Injury

In clinical studies, It is found that the consequence of traumatic brain injury(TBI) appear to worsen with increasing age at each level of brain injury, elderly patients would experience greater acute neurological deficits, higher cognitive morbidity, slower recovery rates, and higher mortality rates than young patients from TBI. We modeled brain injury in aged rats in an effort to elucidate the pathophysiology of this sensitivity and, in particular to determine if there are susceptibility differences in the expression of nerve growth factor(NGF), bcl-2 and bax gene in the brain in young versus aged rats. At last, we observed the effects of β2-adrenoceptor agonist clenbuterol on the expression of NGF,bcl-2 and bax gene in young and aged rats following fluid percussion brain injury, and discussed the protective effect of clenbuterol against brain injury. The research work includes 3 parts:Part I Differential expression of NGF,bcl-2 and bax protein in aged and young rats brain after fluid percussion injury[Abstract] Objective: To study the effect of aging on the expression of NGF,bcl-2 and bax protein after traumatic brain injury(TBI). Methods: TBI was performed in young (2-3 months old) and aged (15 months old) Sprague-Dawley rats by fluid percussion brain injury. The expression of NGF,bcl-2 and bax protein was analyzed by immunohistochemical methods. Results: In the ipsilateral cerebral cortex and hippocampus, the expression of NGF,bcl-2 and bax protein was increased 12h after fluid percussion brain injury both in young and aged rats. However , the level of the NGF protein and the ratio of bcl-2/bax were lower in aged rat cerebral cortex compare to that in the young (P<0.05). Conclusion: The present study demonstrated that the expression of NGF,bcl-2 and bax protein after fluid percussion brain injury was influenced by aging, the low level of NGF expression and the decrease of bcl-2/bax ratio maybe play an important role in the age-related neurological deficits after TBI.Part II Differential induction of NGF,bcl-2 and bax mRNA in aged and young rat following fluid percussion brain injury.[Abstract] Objective To find out whether there are some differences in the expression of NGF, bcl-2 and bax mRNA between the young and aged rats following traumatic brain injuries(TBI). Methods Aged(15 months) and young(2~3 months) Sprague-Dawley rats were subjected to TBI using lateral fluid-percussion brain injury. The expression of NGF,bcl-2 and bax mRNA was analyzed by in situ hybridization and computer image analysis. Results In the ipsilateral cerebral cortex and hippocampus, the expression of NGF,bcl-2 and bax mRNA was increased 12h after fluid percussion brain injury both in young and aged rats. However,the level of NGF and bcl-2 mRNA in the aged rat cerebral cortex was lower than that in the young(the former P<0.05,the later P<0.01),on the contrary, bax mRNA was higher than the young(P<0.01). Conclusion The lower induction of NGF and bcl-2 mRNA and higher induction of bax mRNA after TBI in the elderly maybe elucidate the pathophysiology why the elderly patients have a higher morbidity of neurological deficits.Par III Clenbuterol modulates the expression of NGF, bcl-2 and bax protein and mRNA in aged and young rats following traumatic brain injury [Abstract] Objective To observe the effects of β2-adrenoceptor agonist clenbuterol on the expression of NGF,bcl-2 and bax gene in young and aged rats following traumatic brain injury(TBI), and discuss the protective effect of clenbuterol against brain injury. Methods TBI was performed in young (2-3 months old ) and aged (15 months old) Sprague-Dawley rats by lateral fluid-percussion brain injury. Clenbuterol (0.5mg/kg,intraperitoneally)or vehicle were administered immediately after fluid-percussion injury. The expression of NGF,bcl-2 and bax protein was analyzed by immunohistochemical and in situ hybridization methods. Results Clenbuterol elevated the NGF protein level by 31.4% and 105.9%( the later, P<0.05) in the cortex of the young and aged rats 12 ho...