PMID- 34098454 OWN - NLM STAT- MEDLINE DCOM- 20211216 LR - 20211216 IS - 1532-2785 (Electronic) IS - 0143-4179 (Linking) VI - 88 DP - 2021 Aug TI - Long term neuroprotective effects of acute single dose MK-801treatment against traumatic brain injury in immature rats. PG - 102161 LID - S0143-4179(21)00047-0 [pii] LID - 10.1016/j.npep.2021.102161 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Cigel, Ayse AU - Cigel A AD - Department of Physiology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey. Electronic address: acigel@adu.edu.tr. FAU - Sayin, Oya AU - Sayin O AD - Research Laboratory, Faculty of Medicine Dokuz Eylul University, Izmir, Turkey. Electronic address: oya.sayin@deu.edu.tr. FAU - Gurgen, Seren Gulsen AU - Gurgen SG AD - Department of Histology and Embryology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. FAU - Sonmez, Atac AU - Sonmez A AD - Department of Physiology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey. Electronic address: atac.sonmez@deu.edu.tr. LA - eng PT - Journal Article DEP - 20210521 PL - Netherlands TA - Neuropeptides JT - Neuropeptides JID - 8103156 RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Neuroprotective Agents) RN - 6LR8C1B66Q (Dizocilpine Maleate) SB - IM MH - Animals MH - Brain/drug effects/metabolism MH - Brain Injuries, Traumatic/*drug therapy/metabolism MH - Dizocilpine Maleate/*pharmacology MH - Excitatory Amino Acid Antagonists/pharmacology MH - Hippocampus/drug effects/metabolism MH - Neuroprotective Agents/*pharmacology MH - Rats MH - *Time OTO - NOTNLM OT - BDNF OT - Cognition OT - Hippocampus OT - MK-801 OT - NGF OT - NMDA-R OT - Traumatic brain injury EDAT- 2021/06/08 06:00 MHDA- 2021/12/17 06:00 CRDT- 2021/06/07 20:28 PHST- 2021/01/04 00:00 [received] PHST- 2021/04/28 00:00 [revised] PHST- 2021/05/16 00:00 [accepted] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/12/17 06:00 [medline] PHST- 2021/06/07 20:28 [entrez] AID - S0143-4179(21)00047-0 [pii] AID - 10.1016/j.npep.2021.102161 [doi] PST - ppublish SO - Neuropeptides. 2021 Aug;88:102161. doi: 10.1016/j.npep.2021.102161. Epub 2021 May 21.