title: N-methyl-D-aspartate preconditioning improves short-term motor deficits outcome after mild traumatic brain injury in mice.
abstract: Traumatic brain injury (TBI) causes impairment of fine motor functions in humans and nonhuman mammals that often persists for months after the injury occurs. Neuroprotective strategies for prevention of the sequelae of TBI and understanding the molecular mechanisms and cellular pathways are related to the glutamatergic system. It has been suggested that cellular damage subsequent to TBI is mediated by the excitatory neurotransmitters, glutamate and aspartate, through the excessive activation of the N-methyl-D-aspartate (NMDA) receptors. Thus, preconditioning with a low dose of NMDA was used as a strategy for protection against locomotor deficits observed after TBI in mice. Male adult mice CF-1 were preconditioned with NMDA (75 mg/kg) 24 hr before the TBI induction. Under anesthesia with O(2)/N(2)O (33%: 66%) inhalation, the animals were subjected to the experimental model of trauma that occurs by the impact of a 25 g weight on the skull. Sensorimotor gating was evaluated at 1.5, 6, or 24 hr after TBI induction by using footprint and rotarod tests. Cellular damage also was assessed 24 hr after occurrence of cortical trauma. Mice preconditioned with NMDA were protected against all motor deficits revealed by footprint tests, but not those observed in rotarod tasks. Although mice showed motor deficits after TBI, no cellular damage was observed. These data corroborate the hypothesis that glutamatergic excitotoxicity, especially via NMDA receptors, contributes to severity of trauma. They also point to a putative neuroprotective mechanism induced by a sublethal dose of NMDA to improve motor behavioral deficits after TBI.
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Tayana
authors.initials: T
authors.lastname: Costa
authors.forename: Leandra C
authors.initials: LC
authors.lastname: Constantino
authors.forename: Bruna P
authors.initials: BP
authors.lastname: Mendonça
authors.forename: Josimar G
authors.initials: JG
authors.lastname: Pereira
authors.forename: Bruno
authors.initials: B
authors.lastname: Herculano
authors.forename: Carla I
authors.initials: CI
authors.lastname: Tasca
authors.forename: Carina R
authors.initials: CR
authors.lastname: Boeck
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D016202:N-Methylaspartate