title: Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury.
abstract: OBJECTIVE
  Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses.
  
  
  METHODS
  EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes).
  
  
  RESULTS
  Ten minutes after injury, microglial activation with increased OX42 immuno-reactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions.
  
  
  CONCLUSIONS
  These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suma
authors.forename: Morimichi
authors.initials: M
authors.lastname: Koshinaga
authors.forename: Masamichi
authors.initials: M
authors.lastname: Fukushima
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kano
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007736:Kynurenic Acid / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D039481:CD11b Antigen; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D007473:Ion Channels; D011810:Quinoxalines; D017470:Receptors, Glutamate; D026941:Sodium Channel Blockers; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D007736:Kynurenic Acid; D014633:Valine