An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia

OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 ± 0.7 vs. 85 ± 1.4, mean ± se), and almost blunted neuronal cell death (hippocampal CA1, 2150 ± 191 vs. 884 ± 141 neurons/mm; cortex, 1746 ± 91 vs. 1060 ± 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.