Delayed hemorrhagic hypotension exacerbates the hemodynamic and histopathologic consequences of traumatic brain injury in rats

Yoshitaro Matsushita, Helen M. Bramlett, John W. Kuluz, Ofelia Alonso, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Alterations in cerebral autoregulation and cerebrovascular reactivity after traumatic brain injury (TBI) may increase the susceptibility of the brain to secondary insults, including arterial hypotension. The purpose of this study was to evaluate the consequences of mild hemorrhagic hypotension on hemodynamic and histopathologic outcome after TBI. Intubated, anesthetized male rats were subjected to moderate (1.94 to 2.18 atm) parasagittal fluid-percussion (FP) brain injury. After TBI, animals were exposed to either normotension (group 1: TBI alone, n = 6) or hypotension (group 2: TBI + hypotension, n = 6). Moderate hypotension (60 mm Hg/30 min) was induced 5 minutes after TBI or sham procedures by hemorrhage. Sham-operated controls (group 3, n = 7) underwent an induced hypotensive period, whereas normotensive controls (group 4, n = 4) did not. For measuring regional cerebral blood flow (rCBF), radiolabeled microspheres were injected before, 20 minutes after, and 60 minutes after TBI (n = 23). For quantitative histopathologic evaluation, separate groups of animals were perfusion-fixed 3 days after TBI (n = 22). At 20 minutes after TBI, rCBF was bilaterally reduced by 57% ± 6% and 48% ± 11% in cortical and subcortical brain regions, respectively, under normotensive conditions. Compared with normotensive TBI rats, hemodynamic depression was significantly greater with induced hypotension in the histopathologically vulnerable (P1) posterior parietal cortex (P < 0.01). Secondary hypotension also increased contusion area at specific bregma levels compared with normotensive TBI rats (P < 0.05), as well as overall contusion volume (0.96 ± 0.46 mm3 vs. 2.02 ± 0.51 mm3, mean ± SD, P < 0.05). These findings demonstrate that mild hemorrhagic hypotension after FP injury worsens local histopathologic outcome, possibly through vascular mechanisms.

Original languageEnglish (US)
Pages (from-to)847-856
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number7
StatePublished - 2001


  • Autoregulation
  • Fluid-percussion injury
  • Hypoxia
  • Pathology
  • Rat
  • Regional cerebral blood flow

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism


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