| Objective It has been established from different aspects that the existence of neural progenitor cells in hippocampus plays a beneficial role to cognitive recovery following traumatic brain injury, but the classification-control studies aiming at different graded brain trauma are still insufficient. This experiment tested the capability of adult endogenous neurogenesis for repairing the cognitive function and observed the regeneration status of neural progenitor cells after different graded traumatic hippocampus injury without intervention of external factors to further estimate the significances of endogenous neurogenesis for repairing the injury.Method In terms of complete randomization principle,49 Wistar rats were divided into mild injured group (n=17), severe injured group (n=17) and control group (n=15). The mild injured group and severe injured group were respectively subjected to lateral fluid percussion (LFP) injury of 1.8±0.02 atm and 2.8±0.04 atm,using a precalibrated fluid percussion injury device. Control group was subjected to the same surgical procedure without receiving fluid pulse. To assess the status of newly generated cells after Traumatic brain injury, rats received daily i.p. injection of BrdU at 200 mg/kg body weight for six consecutive days beginning at first day post injury to maximally label the dividing cells.24 hours post injury,3 rats in mild group and 3 rats in severe group were selected and the brains were processed by HE staining to demonstrate the traumatic model was successful.7 days post injury,5 rats in each group were sacrificed to evaluate the proliferative status of newly generated cells through BrdU immunofluorescent staining. The rest of 28 rats were examined in the Morris water maze at 8-12,29-33 and 57-61 days post injury to estimate the cognitive status of hippocampus. Each rat performed 4 trials per day for 5 consecutive days. The time interval needed to find the platform (latency) was the primary dependent variable and the last day's performance of each trial was choosed to assess the hippocampal function.61 days post injury, the rest 28 rats were killed and brains were processed through BrdU/NeuN immunofluorescent staining to evaluate the survival and maturational fate of newly generated cells. We selected representative sections to estimate the number of newly generated cells in hippocampus after different graded traumatic brain injury.Result At 7 days post injury, the BrdU+ cells of hippocampal dentate gyrus increased significantly in mild and severe group compared with the control group (P <0.01).At 61 days post injury, the BrdU+/NeuN+ cells of hippocampal dentate gyrus in mild group were significantly greater than severe group and control group (P< 0.01) and the control group had the greatest proportion of survival cells differentiating to mature neurons (P<0.01)than the other two groups.At 12 and 33 days post injury, the mild group and severe group displayed significant cognitive deficit compared with control group (P<0.01),but at 61 days post injury, the cognitive function of mild group recovered to the normal level,whereas severe group still showed cognitive deficit compared to the other two groups (P<0.01).Conclusion Traumatic brain injury might be a stimulated factor for proliferation of progenitor cells in adult hippocampus at the early stage after injury and an innate repair mechanism existed in hippocampus following injury. Majority of newly generated cells survived for an expended period and differentiated into neurons suggesting that injury induced proliferation was primarily neurogenesis rather than reactive gliosis. More serious brain trauma does not accompany with more new generated cells and only moderate injury could obviously promote endogenous neurogenesis and produce more newly generated neurons to repair the hippocampus dysfunction caused by brain trauma. Endogenous adult neurogenesis can repair neurological function to certain extent. However, in the circumstances of severe traumatic brain injury, the recovery of neurological function is difficult and needs further medical treatments. |
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