Long term neuroprotective effects of acute single dose MK-801treatment against traumatic brain injury in immature rats

Abstract

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.