Neuroprotective effects of MK-801 against traumatic brain injury in immature rats
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2015
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Abstract
Traumatic brain injury (TBI) is a major health problem in pediatric ages and also has major social, economic, and emotional outcomes, with diverse sequelae in many spheres of everyday life. We aimed to investigate the effect of MK-801, a competitive NMDA receptor antagonist, on hippocampal damage and behavioral deficits on 10-day-old rat pups subjected to contusion injury. The aims of the present study were to determine: (i) the short term effects of MK-801 on hippocampal BDNF, NGF and NMDA receptor immunoreactivity and neuron density in hippocampus (ii) long term effects of MK-801 on cognitive dysfunction following TBI in the immature rats. MK-801, was injected intraperitoneally at the doses of 1. mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining, BDNF, NGF and NMDAR receptor immunohistochemistry on P10 day and behavioral alterations were evaluated using elevated plus maze and novel object recognition tests two months after the trauma. Histopathological and immunohistochemical evaluations showed that treatment with a single dose of 1. mg/kg MK-801 (i.p.) significantly ameliorated the trauma induced hippocampal neuron loss and decreased BDNF, NGF and NMDAR expressions in CA1, CA3 and DG hippocampal brain regions. Additionally, treatment with MK-801 ameliorated anxiety and hippocampus dependent memory of animals subjected to trauma. These results show that acute treatment of MK-801 has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in immature rats. © 2015 Elsevier Ireland Ltd.
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Animals , Brain Injuries , Brain-Derived Neurotrophic Factor , Cognition Disorders , Dizocilpine Maleate , Hippocampus , Memory , N-Methylaspartate , Nerve Growth Factor , Neurons , Neuroprotective Agents , Rats, Wistar , brain derived neurotrophic factor , dizocilpine , n methyl dextro aspartic acid receptor , nerve growth factor , brain derived neurotrophic factor , dizocilpine maleate , n methylaspartic acid , nerve growth factor , neuroprotective agent , animal cell , animal experiment , animal model , animal tissue , anxiety , apoptosis , Article , behavior disorder , brain damage , cell density , cognitive defect , controlled study , dentate gyrus , exploratory behavior , hippocampus , immunoreactivity , memory , memory disorder , nerve cell , neuroprotection , nonhuman , novel object recognition test , priority journal , rat , stratum pyramidale , traumatic brain injury , animal , Brain Injuries , Cognition Disorders , drug effects , metabolism , pathology , psychology , Wistar rat