Young children who have sustained severe traumatic brain injury (TBI) can suffer from debilitating neurocognitive deficits. Impairment of adult hippocampal neurogenesis is associated with cognitive deficits and depression. Very few studies have investigated the adult hippocampal neurogenesis after pediatric TBI. Here, we evaluated long-term cognition, adult hippocampal neurogenesis, and microglial activation in a rabbit pediatric TBI model. On Post-natal Day 5-7 (P5-7), New Zealand white rabbits from the same litter were randomized into naïve, sham (craniotomy alone), and TBI (controlled cortical impact). Bromodeoxyuridine (BrdU, 50 mg/kg, intraperitoneally) was administered at 1-month post-injury, once/daily for 5 consecutive days. Novel object recognition and spontaneous alternation in T-maze tests were performed at 2 months post-injury to measure the cognitive functions. The animals were euthanized after behavioral tests at 3 months of age to evaluate adult hippocampal neurogenesis and microglial activation. We found that: 1) pediatric TBI caused significant deficits in hippocampal dependent cognitive functions; 2) the survival rates of adult-born neurons at both ipsilateral and contralateral hippocampus significantly decreased in the TBI group; 3) TBI induced ectopic migration of adult-born neurons at the dorsal dentate gyrus in both ipsilateral and contralateral hippocampus; 4) TBI increased astrogenesis in the hilus of the dentate gyrus; and 5) TBI results in abnormal microglial activation. In conclusion, pediatric TBI causes prolonged neuroinflammation and dysregulation of the adult hippocampal neurogenesis through young adulthood, which might be responsible for the cognitive deficits. Protection of adult hippocampal neurogenesis may potentially improve outcomes.

中文翻译：

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小儿创伤性脑损伤导致成人海马神经发生和认知的长期缺陷。

遭受严重创伤性脑损伤 (TBI) 的幼儿可能会遭受使人衰弱的神经认知缺陷。成人海马神经发生受损与认知缺陷和抑郁症有关。很少有研究调查儿童 TBI 后的成人海马神经发生。在这里，我们评估了兔儿科 TBI 模型中的长期认知、成人海马神经发生和小胶质细胞激活。在产后第 5-7 天 (P5-7)，来自同一窝的新西兰白兔被随机分为幼稚、假手术（仅开颅手术）和 TBI（受控皮质影响）。溴脱氧尿苷（BrdU，50 mg/kg，腹腔注射）在受伤后 1 个月时给药，每天一次，连续 5 天。在受伤后 2 个月进行 T 迷宫测试中的新物体识别和自发交替以测量认知功能。动物在 3 个月大的行为测试后被安乐死，以评估成年海马神经发生和小胶质细胞激活。我们发现：1）小儿TBI导致海马依赖性认知功能显着缺陷；2）TBI组同侧和对侧海马成体神经元存活率均显着降低；3) TBI 诱导同侧和对侧海马背侧齿状回成年出生神经元异位迁移；4) TBI 增加了齿状回门中的星形发生；5) TBI 导致小胶质细胞异常活化。综上所述，小儿 TBI 会导致长期的神经炎症和成年后成年海马神经发生的失调，这可能是导致认知缺陷的原因。保护成年海马神经发生可能会改善结果。