Comparison of experimental rat models of early brain injury after subarachnoid hemorrhage

Abstract

Objective: To investigate acute pathophysiological changes after subarachnoid hemorrhage (SAH) in rats and compare endovascular perforation and double blood injection models for studies of early brain injury after SAH.

Methods: Rat SAH was induced by endovascular perforation of the internal carotid artery (n = 41) or double injection of autologous blood into the cisterna magna (n = 23). Effects of SAH on arterial blood pressure, intracranial pressure, cerebral artery dimensions, and cerebral blood flow were measured. Neuronal death was assessed 24 hours after SAH.

Results: SAH was more severe in the endovascular perforation model (4-fold greater hemoglobin content on the basal brain surface), and mortality was greater (47%) than in the blood injection model (0%). Intracranial pressure increases were faster and greater in the perforation model. Correspondingly, cerebral blood flow reductions were greater after perforation than in the blood injection model, particularly in middle cerebral artery-supplied regions (32 +/- 16 versus 65 +/- 18 mL/100 g/min, P < 0.01). Diffuse neuronal death occurred in all rats in the perforation model but more seldom after blood injection. Anterior cerebral artery diameter and cross sectional area were significantly decreased on day 1 after SAH induction (52 +/- 21% and 22 +/- 16% of control values; P < 0.001) in the perforation model but not after blood injection.

Conclusion: The perforation model produced more severe pathophysiological changes than the double blood injection, and it mimics human SAH in having an injured blood vessel and direct hemorrhagic brain lesion under arterial blood pressure. Therefore, endovascular perforation seems more suitable for study of acute SAH sequelae. However, further model refinement is required to reduce the high mortality rate.