Endogenous opioids may mediate secondary damage after experimental brain injury

T. K. McIntosh, R. L. Hayes, Douglas Dewitt, V. Agura, A. I. Faden

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist {Win 44,441-3 [Win-(-)]} with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume253
Issue number5
StatePublished - 1987
Externally publishedYes

Fingerprint

Opioid Receptors
Cerebrovascular Circulation
Brain Injuries
Opioid Analgesics
Brain
Dynorphins
Regional Blood Flow
Opiate Alkaloids
Wounds and Injuries
Blood
Spinal Cord Ischemia
Percussion
Leucine Enkephalin
Peptide Receptors
Opioid Peptides
Brain Ischemia
Spinal Cord Injuries
Craniocerebral Trauma
Arterial Pressure
Cats

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Endogenous opioids may mediate secondary damage after experimental brain injury. / McIntosh, T. K.; Hayes, R. L.; Dewitt, Douglas; Agura, V.; Faden, A. I.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 253, No. 5, 1987.

Research output: Contribution to journalArticle

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