Abstract T P401: Human Albumin Confers Neurovascular Protection And Long-term Neurobehavioral Improvement After Subarachnoid Hemorrhage

Abstract

Introduction: Subarachnoid hemorrhage (SAH) patients suffer from high mortality and worsening of their daily functioning. Currently no clinically effective agents have been recognized yet. Hypothesis: This study aimed to investigate whether albumin (Alb) confers a sustained improvement in SAH, and whether the salutary effects are associated with neurovascular preservation. Methods: Endovascular perforation method was used to induce SAH. Alb (0.63 g/kg or 1.25 g/kg) was immediately intravenously administered after surgery. Cerebral blood flow and early vasospasm-induced arterial morphology changes were measured to evaluate vascular dysfunction. Fluoro-Jade C staining and TUNEL staining were used to evaluate neuronal injury. To determine the blood-brain barrier (BBB) integrity, EB extravasation, IgG leakage, and tight junction protein levels were assessed. Gelatin zymography was also used to gelatinolytic activity of MMP-2 and MMP-9. Neurological deficits were assessed up to post-operative day 42. Results: SAH grade and mortality were not significantly different among groups. Alb prevented early cerebral blood flow reduction and vasospasm with decreased arterial luminal perimeter, wall thickness and increased arterial diameter as compared with vehicle group. Upon SAH, neuronal degeneration and cell apoptosis were noticed in the hippocampal and cortical areas, which was significantly attenuated by Alb. This neurovascular protection was accompanied with lowered IgG leakage and EB extravasation. Mechanically, the expression levels of tight junction proteins (ZO-1, occludin, claudin-5) and adherent junction protein (VE-cadherin), which maintain the BBB structure and function, were remarkably preserved after treatment of Alb. The expression and activity of gelatinase were also conserved. As for neurological deficits, SAH led to a sensorimotor dysfunction up to 28 days after the insult, which could be improved by Alb. Alb also improved the long-term cognitive outcomes, as assessed by novel object recognition and Morris water maze. Conclusions: In conclusion, Alb preserves neurovascular functions and long-term neurobehavioral outcomes in experimental SAH.