title: Acute treatment with MgSO4 attenuates long-term hippocampal tissue loss after brain trauma in the rat.
abstract: Previous studies have shown that magnesium salts and the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPS 1506, attenuated short-term cognitive deficits and histopathological changes associated with traumatic brain injury (TBI). We evaluated the long-term effects of both therapies after brain trauma. Young adult rats were subjected to parasagittal fluid-percussion brain injury and received either MgSO(4) (125 micromol/400 g rat; n = 12) 15 min post-injury, NPS 1506 (1.15 mg/kg; n = 12) 15 min and 4 hr post-injury, or vehicle (n = 9) 15 min post-injury. Uninjured animals (sham) received vehicle (n = 10). Learning function in these animals was evaluated using a water maze paradigm 8 months after injury or sham treatment, and the brains were examined for cortical and hippocampal tissue loss. Compared to sham animals, injured vehicle-treated animals displayed a substantial learning dysfunction, indicated by an increased latency to find a hidden platform in the water maze (P < 0.001). No improvements in learning, however, were found for injured animals treated with NPS 1506 or MgSO(4). Injury induced >30% loss of tissue in the ipsilateral cortex in vehicle-treated animals that was not reduced in animals treated with either NPS 1506 or MgSO(4). Treatment with MgSO(4) significantly reduced progressive tissue loss in the hippocampus (P < 0.001). These findings are the first to demonstrate long-term neuroprotection of hippocampal tissue by an acute treatment in a TBI model. These data also show that the previously reported broad efficacy of MgSO(4) or NPS 1506 observed shortly after brain trauma could not be detected 8 months post-injury.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Browne
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Leoni
authors.forename: Akira
authors.initials: A
authors.lastname: Iwata
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Chen
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time
chemical_list: D008278:Magnesium Sulfate