Human Serum Albumin Exerts Neurovascular Protections On Early Brain Injury And Long-term Neurological Deficits Following Subarachnoid Hemorrhage

Objective Subarachnoid hemorrhage (SAH) is a life-threatening subtype of neurovascular disease. It is mainly discovered among middle-aged people with high morbidity and mortality. Neurological prognosis after SAH is far beyond satisfaction, especially cognitive impairments which may destroy work and life of survivors. The present study aims to investigate whether human serum albumin (ALB) can exert promotion and neurovascular protection on early brain injury and long-term neurological prognosis following SAH.Methods SD male rats weighing 270-320 g were arranged into four groups:sham, vehicle, ALB 0.63 and ALB 1.25. We used endovascular perforation model to induce SAH. ICP and CBF were monitored during surgery. Physiological parameters were tested before and right after surgery. Vascular perfusion was examined at 6 h after surgery using FITC-dextran; SAH grade, BBB permeability and function, vasospasm and cellular injury were detected at 24 h post-surgery.Alterations of weight ratio, mortality, modified Garcia and beam walking test were evaluated on post-operative day (POD) 1,3,7,14,28. We then used novel object recognition (NOR) to evaluate working memory of SAH rats and Morris water maze (MWM) to assess spatial memory. Golgi staining and western blotting were employed to demonstrate spine density and synaptic related proteins.Results Intravenous infused ALB functioned as a hemodiluent by decreasing hematocrit and increasing plasma colloid oncotic pressure without affecting other physiological values. ALB significantly improved ICP, CBF and vascular hypoperfusion after SAH. Also ALB can reduce BBB permeability, inhibit vasospasm, diminish neuronal degeneration and apoptosis. ALB did not influence long-term weight ratio and mortality changes. However, ALB can significantly improve sensorimotor and coordinate skills of SAH rats in the long run. Furthermore, learning and memory functions were facilitated by both doses of ALB which may function through increasing spine density and synaptic related proteins.Conclusion Intravenous infused ALB of both doses may ameliorate EBI and long-term neurological prognosis through its neurovascular protections following SAH. Cognitive improvements were of great importance which may be via attenuation of spine density shrinkage and snaptic related proteins loss.