ABSTRACT
BACKGROUND:Cerebral hemorrhage can activate the proliferation and differentiation of neural stem cel s in the dentate gyrus of the hippocampus. Through continuous differentiation and proliferation, endogenous neural stem cel s can gradual y replace aging and damaged neurons, thus protecting the brain structure. OBJECTIVE:To compare the difference of the proliferation and differentiation of neural stem cel s in the dentate gyrus of the hippocampus of rats with different ages. METHODS:Ninety-six adult rats and 96 aged rats were randomly divided into normal group (n=18 per group), sham operation group (n=12 per group) and cerebral hemorrhage group (model group, n=66 per group), respectively. Cerebral hemorrhage models were made in the two model groups in which, the rats were subjected to cerebral hemorrhage for 6, 24, 48, 72 hours and 7 days, respectively. Then, brain tissues were col ected to measure brain water content. BrdU/NeuN and BrdU/GFAP double staining were performed at 3, 7, 14, 21, 28 days after surgery to calculate the number of positive cel s. RESULTS AND CONCLUSION:For both adult and aged rats, the brain water content was significantly higher than that in the normal group and sham operation group (P<0.05), while in the normal and sham operation groups, the brain water content was significantly lower in the aged rats than the adult rats (P<0.05). The number of bilateral BrdU-positive cel s in the adult and aged model groups was significantly higher than that in the corresponding normal and sham operation groups (P<0.05), and moreover, the positive cel number at the hemorrhage side was significantly higher than that at the opposite side (P<0.05). In addition, the number of BrdU-positive cel s at the hemorrhage side in the adult rats was significantly higher than that in the aged rats at different time after cerebral hemorrhage (P<0.05). Results from immunohistochemical double staining showed that the BrdU/NeuN and BrdU/GFAP expression in the hippocampal dentate gyrus of adult rats with cerebral hemorrhage was significantly higher than that of normal adult rats. Al these experimental results show that there are a few neural stem cel s proliferating in the hippocampal dentate gyrus of normal rats, and the proliferation ability is stronger in the adult rats than the aged rats. Cerebral hemorrhage can significantly strengthen the proliferation of neural stem cel s in the dentate gyrus in the adult rats compared with the aged rats.
ABSTRACT
BACKGROUND:Previous studies showed that neurotrophic factor has a variety of functions, which can effectively maintain the survival of neurons after injury. OBJECTIVE:To observe the effect of adenovirus-mediated brain-derived neurotrophic factor on the differentiation of endogenous neural stem cels after intracerebral hemorrhage in rats. METHODS:A total of 90 Sprague-Dawley rat models of cerebral hemorrhage were made. At 12 hours after cerebral hemorrhage, 5-bromodeoxyuridine (BrdU) was intraperitonealy injected, twice a day, for 10 consecutive days. After model establishment, rats were randomly divided into three groups, 30 rats in each group, and were respectively subjected to brain stereotaxic injection of adenovirus vector, adenovirus-mediated brain-derived neurotrophic factor and physiological saline. At 1 day, 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks, neurological deficit score was evaluated. Absorbancevalue of growth associated protein around the area of hematoma after intracerebral hemorrhage was measured. At 4 weeks after injection, double immunostaining was used to detect the expression of BrdU/NeuN and BrdU/glial fibrilary acidic protein (GFAP). RESULTS AND CONCLUSION:(1) With the passage of time, nerve function defect score decreased in the three groups. At 1-4 weeks after injection, nerve function deficit scoreswere lower in the adenovirus-mediated brain-derived neurotrophic factor group thanthat in the adenovirus vector group and saline group (P< 0.05). (2) With the passage of time, the average absorbance of three groups in the peri-hematoma region first increased and then decreased. The absorbance value was higher in the adenovirus-mediated brain-derived neurotrophic factor group than in the adenovirus vector group and saline group at 3 days-4 weeks (P< 0.05). (3) BrdU/NeuN and BrdU/GFAP rates were significantly higher in the adenovirus-mediated brain-derived neurotrophic factor group thanthat of adenovirus vector group and saline group (P< 0.05). (4) The results show that the brain-derived neurotrophic factor mediated by adenovirus, and intervention on cerebral hemorrhage in rats can effectively promote the differentiation of endogenousneural stem cels, and promote the recovery of neural function in animal.