Introduction: A significant portion of the morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH) is due to delayed ischemic neurological deficits (DIND). Although large vessel vasospasm has been implicated as a cause of DIND, the presence of such spasm is not always correlated with DIND. We examined the cortical microvasculature as well as cerebral perfusion in awake mice after SAH in an experimental model typically associated with large vessel vasospasm.
Methods: Twenty adult mice underwent cisterna magna (CM) injection of 60ul syngenic donor blood or artificial cerebrospinal fluid (aCSF). The mice were perfused at 72 hours, and Circle of Willis (COW) vessel diameters were measured. In a separate experiment, cranial windows were created in 10 mice that then underwent CM blood or aCSF injection. Cortical microvessels were measured in awake mice in the vasospasm period using two photon laser scanning microscopy. We also examined sensory-evoked increases in cerebral perfusion using laser Doppler and cerebral blood volume measurements.
Results: We observed a statistically significant difference in COW vessel diameter between the experimental and control groups at each of the sites measured (MCA, P=0.0259; ACA, P=0.0012). In the second experiment, there were no significant differences in cortical microvessel diameter between the experimental and control groups. There were no differences in sensory-evoked increases in cerebral perfusion.
Conclusions: In a CM injection SAH model, we observed significant large vessel spasm but no cortical microvessel spasm or cerebral blood flow change. These results may have important implications for understanding the mechanisms of DIND.
Patient Care: Our experiments are designed to uncover mechanisms of vasospasm and delayed ischemic neurological deficits (DIND) following subarachnoid hemorrhage. An improved understanding of the pathophysiology of DIND will lead to improved treatments for this devastating disease
Learning Objectives: 1. Describe results of experiments designed to test putative mechanisms of vasospasm and delayed ischemic neurological deficits (DIND)
2. Explore implications of the results of these experiments for understanding DIND pathopysiology and treatments
References: Drew PJ, Shih AY, Driscoll JD, Knutsen PM, Blinder P, Davalos D, Akassoglou K, Tsai PS, Kleinfeld D. Chronic optical access through a polished and reinforced thinned skull. Nat Methods. 2010; 7(12):981-4.
Koide M, Bonev AD, Nelson MT, Wellman GC. Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca2+-activated K+ (BK) channels. Proc Natl Acad Sci U S A. 2012;109(21):E1387-95.
Østergaard L, Aamand R, Karabegovic S, Tietze A, Blicher JU, Mikkelsen IK, Iversen NK, Secher N, Engedal TS, Anzabi M, Jimenez EG, Cai C, Koch KU, Naess-Schmidt ET, Obel A, Juul N, Rasmussen M, Sørensen JC. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2013;33(12):1825-37.
Lin CL, Calisaneller T, Ukita N, Dumont AS, Kassell NF, Lee KS. A murine model of subarachnoid hemorrhage-induced cerebral vasospasm. J Neurosci Methods. 2003;123(1):89-97.