Hippocampal cellular loss after brief hypotension

Abstract

Brief episodes of hypotension have been shown to cause acute brain damage in animal models. We used a rat hemorrhagic shock model to assess functional outcome and to measure the relative neuronal damage at 1, 4 and 14 days post-injury (3 min of hypotension). All rats underwent a neurological assessment including motor abilities, sensory system evaluation and retrograde memory at post-hypotensive insult. Brains were harvested and stained for Fluorojade C and Nissl. Stereology was used to analyze Fluorojade C and Nissl stained brain sections to quantitatively detect neuronal damage after the hypotensive insult. Statistical analysis was performed using Graphpad Prism 5 with the Bonferroni test at a 95% confidence interval after ANOVA. A Mixed Effect Model was used for the passive avoidance evaluation. Stereologically counted fluorojade positive cells in the hippocampus revealed significant differences in neuronal cell injury between control rats and rats that received 3 min of hypotension one day after insult. Quantification of Nissl positive neuronal cells showed a significant decrease in the number hippocampal cells at day 14. No changes in frontal cortical cells were evident at any time, no significative changes in neurological assessments as well. Our observations show that brief periods of hemorrhage-induced hypotension actually result in neuronal cell damage in Sprague–Dawley rats even if the extent of neuronal damage that was incurred was not significant enough to cause changes in motor or sensory behavior.