Experimental Subarachnoid Hemorrhage in Rats: Comparison of Two Endovascular Perforation Techniques with Respect to Success Rate, Confounding Pathologies and Early Hippocampal Tissue Lesion Pattern

Abstract

Recently aside from the "classic" endovascular monofilament perforation technique to induce experimental subarachnoid hemorrhage (SAH) a modification using a tungsten wire advanced through a guide tube has been described. We aim to assess both techniques for their success rate (induction of SAH without confounding pathologies) as primary endpoint. Further, the early tissue lesion pattern as evidence for early brain injury will be analyzed as secondary endpoint. Sprague Dawley rats (n=39) were randomly assigned to receive either Sham surgery (n=4), SAH using the "classic" technique (n=18) or using a modified technique (n=17). Course of intracranial pressure (ICP) and regional cerebral blood flow (rCBF) was analyzed; subsequent pathologies were documented either 6 or 24 h after SAH. Hippocampal tissue samples were analyzed via immunohistochemistry and western blotting. SAH-induction, regardless of confounding pathologies, was independent from type of technique (p=0.679). There was no significant difference concerning case fatality rate (classic: 40%; modified: 20%; p=0.213). Successful induction of SAH without collateral ICH or SDH was possible in 40% with the classic and in 86.7% with the modified technique (p=0.008). Peak ICP levels differed significantly between the two groups (classic: 94 +/- 23 mmHg; modified: 68 +/- 19 mmHg; p=0.003). Evidence of early cellular stress response and activation of apoptotic pathways 6 h after SAH was demonstrated. The extent of stress response is not dependent on type of technique. Both tested techniques successfully produce SAH including activation of an early stress response and apoptotic pathways in the hippocampal tissue. However, the induction of SAH with less confounding pathologies was more frequently achieved with the modified tungsten wire technique.