A well-characterized mouse model of subarachnoid hemorrhage (SAH) that reproduces the pathophysiology of acute clinical SAH does not exist. Such a model would permit the use of transgenic technology to examine the contribution of genes and products that contribute to acute ischemic injury after SAH. The goal of this study is to develop/characterize a mouse model of SAH, and use it to study Nitric Oxide Synthase (NOS) knockouts during the acute phase of SAH. The hypothesis of this study is that an endovascular filament model of SAH in the mouse can be developed to study acute cerebral ischemia after SAH using transgenic technology.
The Specific aims are 1) to develop the endovascular monofilament model of SAH in the mouse, 2) to characterized the pathophysiology of SAH in this model, and 3) to study NOS knockouts using the model. We previously developed the rat endovascular model of SAH that is used by other workers in this area. The mouse model will be developed using similar techniques adapted to the decreased size of this animal. Endpoints used in characterization of the mouse SAH model will include measurements of blood pressure, intracranial pressure, bilateral cerebral blood flow and histological measurements of the severity of SAH and the degree of vasoconstriction. The utility of a mouse model of SAH will be determined by using knock out mice for endothelial-, neuronal-, or inducible NOS. The contribution of each NOS isozyme to acute changes of Nitric Oxide (NO) levels after SAH will be assessed. This investigation will extend previous Findings from our laboratory using the rat SAH model. The long-term goal of this grant is to develop a mouse SAH model to study the contribution of genes and their products to ischemic cerebral damage during the eady phases of SAH. Significance: development of a mouse SAH model could lead to new therapeutic options against acute cerebral injury after SAH. ? ?
| Sefcik, Roberta K; Rasouli, Jonathan; Bederson, Joshua B et al. (2017) Three-Dimensional, computer simulated navigation in endoscopic neurosurgery. Interdiscip Neurosurg 8:17-22 |
| Sehba, Fatima A; Flores, Rowena; Muller, Artur et al. (2010) Adenosine A(2A) receptors in early ischemic vascular injury after subarachnoid hemorrhage. Laboratory investigation. J Neurosurg 113:826-34 |
