Cerebral Ischemia after Bilateral Carotid Artery Occlusion and Intraluminal Suture Occlusion in Mice: Evaluation of the Patency of the Posterior Communicating Artery

Abstract

Summary: Cerebral ischemia models using mice have drawn increasing attention, particularly because of the availability of transgenic animals, However, the variability of intracranial vas culature at the circle of Willis in mice can influence the degree of ischemia in both the bilateral common carotid artery (CCA) occlusion and intraluminal suture occlusion models, We have developed a method to predict the extent of the anastomosis between carotid and vertebrobasilar circulation in three mouse strains (C57BLl6, CBA, and DBAl2) by measuring cortical microperfusion with laser Doppler flowmetry during a 1-minute occlusion of both CCA, When animals showed residual cortical microperfusion of less than 12% during bilateral CCA occlusion, the mice showed absence of functional anastomosis, developed ATP depletion in the frontal cortex during occlusion,The patency of the posterior communicating artery (PComA) has been regarded as a crucial factor in the development of forebrain ischemia after bilateral com mon carotid artery (CCA) occlusion in gerbils (Levine and Sohn, 1969;Kahn, 1972; Berry et aI., 1975), In mice, strain differences have been observed regarding the pa tency of the PComA at the circle of Willis (Barone et a!., 1993; Yang et aI., 1997), Although the territory supplied by the posterior cerebral artery (PCA), including the hip pocampus and thalamus, is expected to experience isch- emia using the intraluminal suture occlusion model in the absence of collateral circulation through a patent PComA (Fig. 1), the importance of the PComA has not been critically evaluated in the context of an intraluminal su ture occlusion model to produce occlusion of the middle cerebral artery (MCA), In the current study, we provide evidence that patency of the PComA is a crucial deter minant of the development of bilateral forebrain isch emia after bilateral CCA occlusion as well as ischemia in the PCA territory using the intraluminal suture occlusion model in three murine strains, including C57BL/6, CBA, and DBA12. We therefore developed a procedure to pre dict the patency of the PComA and found that this pro cedure would be useful for the reproducible induction of cerebral ischemia in transgenic mice. MATERIALS AND METHODSThree mouse strains were obtained from Charles River, Inc.(Yokohama, Kanagawa, Japan): C57BLl6NCrj (C57BLl6), CBAljNCrj (CBA), and DBAl2NCrj (DBAl2). All mice were mature males aged 8 to 16 weeks, weighing 22.5 ± 0.4 g (C57BLl6, n = 46), 21.8 ± 0.6 g (CBA, n = 27), and 22.8 ±

p53 Potentiates Hippocampal Neuronal Death Caused by Global Ischemia

“…Since this method yields highly reproducible and consistent CA1 neuronal injury, as compared with other models (Kitagawa et al, 1998;Wellons et al, 2000), comparison of ischemic outcomes in wild-type and p53-deficient mice could show a link between p53 and ischemic neuronal injury in vivo.…”

On Ischemic Brain Injury in Genetically Altered Mice

“…This appears to be the case in the study of Tabrizi et al 34 Interstrain differences in intracranial vascular anatomy affecting the circle of Willis are another factor influencing the degree of ischemia. [45][46][47][48] As the methods of molecular biology and genetics continue to be applied with increasing success to the study of ischemic brain injury, one expects not only an increasingly sophisticated understanding of pathophysiology but also major advances in the rational design and implementation of neuroprotective strategies that will be tested in the clinic and succeed, eventually, in diminishing death and disability in patients with ischemic stroke. …”

Optimized protocol to reduce variable outcomes for the bilateral common carotid artery occlusion model in mice

“…It is now apparent that the sensitivities to ischemic insult between different mouse strains is a problematic issue (Sheldon et al, 1998;Wellons et al, 2000) that necessitates optimizing ischemic duration for each mouse strain. In addition, we and others have noted variability stemming from individual differences in collateral flow through the circle of Willis, even within one strain (Fujii et al, 1997;Kitagawa et al, 1998;Sheng et al, 1999;Beckmann, 2000;Wellons et al, 2000). Therefore, knowing the patency of PcomA of an individual mouse before conducting surgery would be ideal for optimizing this model.…”

“…Therefore, knowing the patency of PcomA of an individual mouse before conducting surgery would be ideal for optimizing this model. Some investigators have suggested that residual cerebral blood flow (rCBF) after the initiation of ischemia could be used as a predictor of the presence of PcomA (Kitagawa et al, 1998;Yonekura et al, 2004). It was also reported that mice undergoing transient global ischemia by 3-vessel occlusion in which the effect of collateral blood flow had been eliminated by successful basilar artery occlusion would have a rCBF <10% of baseline at 2.5 min after ischemia was initiated (Yonekura et al, 2004).…”