title: Neuroprotective effects of MK-801 against traumatic brain injury in immature rats.
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 1mg/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 1mg/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.
authors.affiliation: Department of Physiology, Faculty of Medicine, Dokuz Eylül University, 35340 Izmir, Turkey. Electronic address: atac.sonmez@deu.edu.tr.
authors.forename: Ataç
authors.initials: A
authors.lastname: Sönmez
authors.affiliation: Research Laboratory, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Oya
authors.initials: O
authors.lastname: Sayın
authors.affiliation: Department of Histology and Embriyology, Medical Faculty, Celal Bayar University, Manisa, Turkey.
authors.forename: Seren Gülşen
authors.initials: SG
authors.lastname: Gürgen
authors.affiliation: Health Science Institute, Laboratory Animal Science, Dokuz Eylül University, Izmir, Turkey.
authors.forename: Meryem
authors.initials: M
authors.lastname: Çalişir
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008568:Memory / Q000187:drug effects; D016202:N-Methylaspartate / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D020932:Nerve Growth Factor
keywords: BDNF; Cognition; Hippocampus; Immature rats; MK-801; NGF; NMDAR; Traumatic brain injury