Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats

L. W. Jenkins, Y. C. Lu, W. E. Johnston, B. G. Lyeth, Donald Prough

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Muscarinic and NMDA receptors contribute to post-traumatic hypersensitivity to secondary ischemia. However, the effect of these receptor antagonists on behavior and CA1 neuronal death after traumatic brain injury (TBI) with acute (1 h after TBI) forebrain ischemia has not been systematically assessed. We examined cognitive and motor dysfunction and the relationship of behavior deficits to neuronal death in this model using muscarinic and NMDA antagonists. Three behavioral groups (n = 10/group) of Wistar rats: were subjected to mild TBI and 6 rain of forebrain ischemia imposed 1 h after TBI with 45 clays survival. Motor and spatial memory performance were assessed using the rotarod task and Morris water maze. Seven additional groups (n = 6/group) were evaluated only for CA 1 death after 7 days survival following sham, individual or combined injury with and without drug treatments. Rats were given 0.3 mg/kg MK-801 (M) and 1.0 mg/kg scopolamine (S) alone or combined (M-S) before or 45 min after TBI. Rotarod performance was tested at days 1-5 and maze performance on days 11-15 and 40- 44 after M-S treatment. The 7-day studies showed M-S treatment (p < 0.01) reduced CA1 neuronal death better than either S or M alone. Behavioral groups had inadvertent post-ischemic hypothermia that decreased CA1 death and likely influenced behavioral morbidity. M-S given before TBI (p < 0.01) decreased memory deficits on day 15, while M-S treatment given after TBI was ineffective. Unexpectedly, M-S treatment before or after TBI produced transient motor deficits (p < 0.01). Memory improvement occurred independent of CA1 death.

Original languageEnglish (US)
Pages (from-to)132-144
Number of pages13
JournalBrain Research
Volume817
Issue number1-2
DOIs
StatePublished - Jan 30 1999

Fingerprint

Brain Concussion
Prosencephalon
Ischemia
Therapeutics
Muscarinic Antagonists
Scopolamine Hydrobromide
Dizocilpine Maleate
Rain
Memory Disorders
Muscarinic Receptors
N-Methylaspartate
Traumatic Brain Injury
N-Methyl-D-Aspartate Receptors
Hypothermia
Wistar Rats
Hypersensitivity
Morbidity
Water
Wounds and Injuries

Keywords

  • Cerebral ischemia
  • Excitotoxicity
  • Hippocampus
  • Hypothermia
  • Rat
  • Spatial memory
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats. / Jenkins, L. W.; Lu, Y. C.; Johnston, W. E.; Lyeth, B. G.; Prough, Donald.

In: Brain Research, Vol. 817, No. 1-2, 30.01.1999, p. 132-144.

Research output: Contribution to journalArticle

Jenkins, L. W. ; Lu, Y. C. ; Johnston, W. E. ; Lyeth, B. G. ; Prough, Donald. / Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats. In: Brain Research. 1999 ; Vol. 817, No. 1-2. pp. 132-144.
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