Investigation of the effects of nimodipine and enoxaparin sodium on changes in the glymphatic system after subarachnoid hemorrhage in rabbits

Objective: Subarachnoid hemorrhage (SAH) is the presence of blood in the subarachnoid space and is a sign of serious brain disease. It accounts for 5% of all cerebral strokes, with an incidence of 10/100000/person/year. Following the first demonstration of the brain glymphatic system in 2012, studies have shown that the glymphatic system plays a role in the clearance of brain metabolic wastes. The aim of this study was to evaluate the relationship between the glymphatic system and pathophysiologic events affecting clinical outcomes in a rabbit model of SAH and to investigate whether nimodipine and enoxaparin sodium are effective in clinical outcomes. Materials and Methods: In the study, 20 white male New Zealand rabbits weighing 3000-4000 g were used. MR cisternography imaging, neurologic functions, food intake, age/dry weight measurements of the brain, and hematoxylin and eosin staining of brain tissue samples were performed between the control group and the groups in which SAH was performed and no medication was given, or SAH was performed and enoxaparin or nimodipine treatment was started. For the evaluation of inflammatory processes, S100B, NSE levels in cerebrum, serum and deep cervical lymph tissues, cerebrum Aqp4 gene expression levels were compared between the groups. Results: In the groups receiving enoxaparin sodium and nimodipine treatments after SAH; - significant improvement in neurologic functions and food intake values, - In MR cisternography results, early phase (day 1) images showed accumulation of contrast material in the CSF space around the optic and olfactory nerves, ventricular system, internal acoustic canals and inner ear structures, main and accessory olfactory bulbs, vomeronasal nerves, facial and nasal veins, and late phase (days 3 and 5) images showed almost complete clearance of contrast material and presence of contrast material in the bladder. - (results of wet/dry weight measurements) were effective in reducing brain edema, - Aqp4 gene expression levels were lower, - There are fewer areas of edema in histologic studies, - decreased in light microscopy evaluation of the perivascular area/vascular area ratio, which helps to assess glymphatic flow, - Serum and lymph tissue levels of S100B and NSE, which are used as inflammatory markers, were found to be significantly higher in the untreated group. Conclusion: Rabbits treated with nimodipine and enoxaparin sodium after SAH; - had significant improvement in neurologic functions and food intake, whereas there was no improvement in the untreated group, - MR cisternography imaging showed no significant difference in glymphatic flow between the groups and no increase in SAH rates, especially in the enoxaparin group, - enoxaparin sodium has antithrombic, anticoagulant, profibrinolytic and anti-inflammatory effects on the glymphatic system and nimodipine prevents vasospasm and reduces cerebral edema, - the effects of drugs lead to an increase in S100B, NSE in serum and lymph tissue and a decrease in Aqp4 gene expression levels, - We observed statistically and histologically significant differences in the wet/dry weight measurements, perivascular area/vascular area ratios of the brain. Keywords: Subarachnoid Hemorrhage, Glymphatic System, Enoxaparin Sodium, Nimodipine