A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat

Eiji Tsuchida, John F. Harms, John J. Woodward, Ross Bullock

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Acute subdural hematoma kills or disables more severely head injured patients than any other complication of cranial trauma. The main pathological factor involved is ischemic neuronal damage, which is caused by raised intracranial pros sure and local effect. The authors have evaluated the hypothesis thai a novel use-dependent sodium channel antagonist. 619C89, could reduce ischemic brain damage in the rat subdural hematoma model. Because previous studies have shown that focal neuronal damage may be mediated by 'excitotoxic' mechanisms, and because excitatory amino acid levels have been shown to be markedly elevated after brain trauma in humans, the authors have measured levels of glutamate, aspartate, and threonine within the cortex underneath the hematoma, using in vivo microdialysis before and after induction of hematoma, in both vehicle and drug-treated rats. Postinjury treatment with 619C89 (30 mg/kg) significantly reduced the volume of hemispheric ischemic damage produced by subdural hematoma, from 99.77 ± 7.51 mm3 in vehicle-treated control rats to 46.07 ± 11.06 mm3 (p = 0.0007) in drug-treated animals. In the vehicle-treated animals, induction of subdural hematoma led to a fourfold increase in glutamate in the first 30 minutes after subdural hematoma occurred. The mean extracellular glutamate concentration in these animals remained 2- to 2.6-fold increased over the following 2.5 hours. In the 619C89-treated animals, the release of glutamate from the cortex underneath the hematoma was significantly attenuated. In these rats, induction of subdural hematoma led to a 2.7-fold increase in the first 30-minute sample, but extracellular glutamate concentration returned to near-basal levels thereafter, compared with vehicle-treated animals (p < 0.05). These results show thai 619C89 is highly neuroprotective in this model and that its effects may, in part, be mediated by the inhibiton of glutamate release from the ischemic cortex underneath the hematoma.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalJournal of Neurosurgery
Volume85
Issue number1
StatePublished - Jul 1 1996
Externally publishedYes

Fingerprint

Hematoma, Subdural, Acute
Sodium Channels
Subdural Hematoma
Glutamic Acid
Hematoma
Brain
Excitatory Amino Acids
Microdialysis
Threonine
Aspartic Acid
Pharmaceutical Preparations
sipatrigine
Head
Wounds and Injuries

Keywords

  • 619C89
  • acute subdural hematoma
  • excitatory amino acid sodium channel antagonist
  • rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat. / Tsuchida, Eiji; Harms, John F.; Woodward, John J.; Bullock, Ross.

In: Journal of Neurosurgery, Vol. 85, No. 1, 01.07.1996, p. 104-111.

Research output: Contribution to journalArticle

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