Effect of duration of osmotherapy on blood-brain barrier disruption and regional cerebral edema after experimental stroke

Chih Hung Chen, Thomas J K Toung, Adam Sapirstein, Anish Bhardwaj

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Osmotherapy is the cornerstone of medical management for cerebral edema associated with large ischemic strokes. We determined the effect of duration of graded increases in serum osmolality with mannitol and hypertonic saline (HS) on blood-brain barrier (BBB) disruption and regional cerebral edema in a well-characterized rat model of large ischemic stroke. Halothane-anesthetized adult male Wistar rats were subjected to transient (2-h) middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Beginning at 6 h after MCAO, rats were treated with either no intravenous fluids or a continuous intravenous infusion (0.3 mL/h) of 0.9% saline, 20% mannitol, 3% HS, or 7.5% HS for 24, 48, 72, and 96 h. In the first series of experiments, BBB permeability was quantified by the Evans blue (EB) extravasation method. In the second series of experiments, water content was assessed by comparing wet-to-dry weight ratios in six predetermined brain regions. Blood-brain barrier disruption was maximal in rats treated with 0.9% saline for 48 h, but did not correlate with increases in serum osmolality or treatment duration with osmotic agents. Treatment with 7.5% HS attenuated water content in the periinfarct regions and all subregions of the contralateral nonischemic hemisphere to a greater extent than mannitol did with no adverse effect on survival rates. These data show that (1) BBB integrity is not affected by the duration and degree of serum osmolality with osmotic agents, and (2) attenuation of increases in brain water content with HS to target levels >350 mOsm/L may have therapeutic implications in the treatment of cerebral edema associated with ischemic stroke.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume26
Issue number7
DOIs
StatePublished - Jun 19 2006
Externally publishedYes

Fingerprint

Brain Edema
Blood-Brain Barrier
Mannitol
Stroke
Osmolar Concentration
Middle Cerebral Artery Infarction
Serum
Evans Blue
Water
Brain
Halothane
Therapeutics
Intravenous Infusions
Wistar Rats
Permeability
Weights and Measures

Keywords

  • Cerebral edema
  • Focal cerebral ischemia
  • Infarct
  • Osmotherapy
  • Reperfusion
  • Stroke

ASJC Scopus subject areas

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

Cite this

Effect of duration of osmotherapy on blood-brain barrier disruption and regional cerebral edema after experimental stroke. / Chen, Chih Hung; Toung, Thomas J K; Sapirstein, Adam; Bhardwaj, Anish.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 26, No. 7, 19.06.2006, p. 951-958.

Research output: Contribution to journalArticle

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