Because brain development continues during adolescence, childhood trauma is a major health problem in pediatric ages. It is known traumatic brain injury (TBI) results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The study aims to investigate the long-term effects of MK-801 (dizocilpine), an N-methyl d-aspartate (NMDA) receptor antagonist, on hippocampal damage, locomotor activity, and cognitive functions following TBI in immature rats. MK-801 (1 mg/kg) was injected intraperitoneally immediately after TBI. Thirty-seven litters were randomly allocated into three groups at 7 days (P7) of postnatal age: a control group, a trauma group, and an MK-801 treatment group. The control group received no treatment; the trauma group received saline as vehicle control for the MK-801 group and the MK-801 group received a single dose of 1 mg/kg MK-801 immediately after TBI. Hippocampal damage was examined by Hematoxylin-Eosin staining. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), NMDA-R, and glial fibrillar acidic protein (GFAP) immunohistochemistry and, BDNF, NGF, and NMDA-R ELISA protein levels were evaluated 125 days after trauma. Histopathological and immunohistochemical evaluations showed that treatment with MK-801 significantly ameliorated the trauma-induced hippocampal neuron loss and increased BDNF, NGF, NMDA-R, GFAP expressions in CA1, CA3, and DG hippocampal regions. Additionally, treatment with MK-801 decreased anxiety and increased hippocampus-dependent memory of animals subjected to brain injury after TBI. These results show that acute treatment of MK-801 has a neuroprotective role against trauma-induced hippocampal neuron loss and associated cognitive impairment in rats.

由于大脑在青春期继续发育，因此童年创伤是儿童时期的主要健康问题。众所周知，外伤性脑损伤 (TBI) 会导致大脑的海马和皮质区域受损并损害认知功能。该研究旨在调查 MK-801（地佐西平）的长期影响，这是一种N-甲基d-天冬氨酸 (NMDA) 受体拮抗剂，对未成熟大鼠 TBI 后的海马损伤、运动活动和认知功能有影响。TBI 后立即腹膜内注射 MK-801 (1 mg/kg)。在出生后 7 天 (P7) 将 37 窝幼仔随机分为三组：对照组、创伤组和 MK-801 治疗组。对照组不接受治疗；创伤组接受生理盐水作为 MK-801 组的载体对照，MK-801 组在 TBI 后立即接受单剂量 1 mg/kg MK-801。通过苏木精-伊红染色检查海马损伤。在创伤后 125 天评估脑源性神经营养因子 (BDNF)、神经生长因子 (NGF)、NMDA-R 和胶质纤维酸性蛋白 (GFAP) 免疫组织化学以及 BDNF、NGF 和 NMDA-R ELISA 蛋白水平。组织病理学和免疫组织化学评估表明，MK-801 治疗显着改善了创伤引起的海马神经元丢失，并增加了 CA1、CA3 和 DG 海马区的 BDNF、NGF、NMDA-R、GFAP 表达。此外，用 MK-801 治疗可减少 TBI 后脑损伤动物的焦虑并增加海马依赖性记忆。这些结果表明，MK-801 的急性治疗对大鼠外伤引起的海马神经元丢失和相关的认知障碍具有神经保护作用。用 MK-801 治疗减少了 TBI 后脑损伤动物的焦虑并增加了海马依赖性记忆。这些结果表明，MK-801 的急性治疗对大鼠外伤引起的海马神经元丢失和相关的认知障碍具有神经保护作用。用 MK-801 治疗减少了 TBI 后脑损伤动物的焦虑并增加了海马依赖性记忆。这些结果表明，MK-801 的急性治疗对大鼠外伤引起的海马神经元丢失和相关的认知障碍具有神经保护作用。