Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats

Robert S B Clark, Patrick M. Kochanek, Margaret A. Schwarz, Joanne K. Schiding, David S. Turner, Minzhi Chen, Timothy M. Carlos, Simon C. Watkins

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The inflammatory response after traumatic brain injury (TBI) includes cytokine production, leukocyte infiltration, and microglial activation. Production of nitric oxide by inducible nitric oxide synthase (iNOS) occurs during acute inflammation outside of the CNS and in models of cerebral ischemia, and therefore may contribute to the inflammatory response after TBI. The purpose of this study was to localize and define the time course of iNnS expression after TBI in the immature rat. Immature Wistar rats (age 3.5- 4.5 wk) were anesthetized and subjected to percussive trauma to the right parietal cortex. Nontraumatized rats were used as controls (n = 7). At 2, 24, 48, or 168 h (n = 3/group) posttrauma rats were killed by perfusion fixation. Brains were removed, frozen, sectioned, immunostained with antibodies against iNnS and glial fibrillary acidic protein (GFAP, a marker specific for astrocytes), and imaged using fluorescent detection systems. There was no detectable expression of iNnS in control brains. At 2 h, minimal cerebrovascular iNnS expression was seen in the peritrauma area. At 24 and 48 h, there was marked peritrauma cerebrovascular iNnS expression that appeared to be restricted to vascular smooth muscle cells and infiltrated leukocytes. Further dual-immunolabeling showed that the leukocytes expressing iNnS were predominantly neutrophils. At 168 h, iNnS expression was no longer detectable. iNOS was not detectable in GFAP-positive cells. The prominent expression of iNnS protein after TBI in cerebrovascular smooth muscle cells and infiltrated neutrophils suggests that iNnS may play a role in cerebrovascular disturbances and secondary brain injury after trauma.

Original languageEnglish (US)
Pages (from-to)784-790
Number of pages7
JournalPediatric Research
Volume39
Issue number5
DOIs
StatePublished - May 1996

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Clark, R. S. B., Kochanek, P. M., Schwarz, M. A., Schiding, J. K., Turner, D. S., Chen, M., Carlos, T. M., & Watkins, S. C. (1996). Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatric Research, 39(5), 784-790. https://doi.org/10.1203/00006450-199605000-00007