Characterization of an improved double hemorrhage rat model for the study of delayed cerebral vasospasm

Abstract

Rats have been shown in several studies to develop delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the rat model has not yet been fully validated, and there are number of methodological issues. In this study, we present an improved double hemorrhage rat model for studies of delayed cerebral vasospasm. Double hemorrhage was induced at an interval of 24 h using a PE-10 catheter introduced into the cisterna magna through a parieto-occipital burr hole. Blood volumes consisted of 0.3/0.2 ml (Group 1) or 0.2/0.1 ml (Group 2). Regional cerebral blood flow (CBF) was measured with 14C-IMP, and compared to a sham operated control group. Additionally, the diameter and cross-sectional area of basilar artery (BA) was measured microscopically at four different levels. Mortality in Group 1 was 40%, compared to 1.5% in Group 2 and further experiments focused on the latter. Immediately following the second hemorrhage, the vessel diameter and cross-sectional area of BA were not significantly changed, but by day 5 these had decreased to 64 ± 3% and 39 ± 4% of control ( p < 0.001), respectively. CBF changes were global, affecting all cerebral areas to a similar degree. Immediately following second SAH induction, CBF diminished to 62–73% of control ( p < 0.05). By day 1, CBF had slightly increased above normal (101–120%), but there was then a second progressive reduction in flow in all areas examined at day 5 reaching 70–85% of baseline ( p < 0.05). CBF then normalized by day 7 and 9. In this study, we present a new technique for creation of double SAH leading to delayed cerebral vasospasm in rats.