Distal hypoxic stroke: A new mouse model of stroke with high throughput, low variability and a quantifiable functional deficit

Abstract

C57BL/6J are the most commonly used strain of mouse for stroke experiments but vascular anatomy of the Circle of Willis within this strain is extremely variable and the cortex has extensive collateralization. This causes large variability in stroke models that target the middle cerebral artery proximally and confers resistance to ischemia in those that target it distally. We tested the hypothesis that by combining distal middle cerebral artery occlusion with 1 hour of hypoxia, we could generate a large lesion that causes a behavioral deficit with low variability. We found that this new distal hypoxic (DH) model of stroke generates a lesion with a volume of 25% of the ipsilateral hemisphere, extends to the motor cortex and causes a behavioral deficit. It also has a very clear border, exceptionally low variability, and can be performed by a single surgeon on up to 30 animals a day. Moreover, survivability is 100% in young adult animals, the model can be performed on old animals, and therapeutic intervention can reduce infarct volume. Therefore DH stroke is an excellent complement to existing stroke models and could be used for preclinical studies in C57BL/6J mice.

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

“…26 For this set of studies, ventral photographs of carbon-black-perfused brains revealed that the posterior communicating artery was present either unilaterally or bilaterally in all mice except one.…”

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

“…Distal middle cerebral artery occlusion (DMCAO) plus hypoxia (DH stroke) was performed on C57BL/6 mice, as previously described (Doyle et al, 2012; Nguyen et al, 2016). Mice were anesthetized by isoflurane inhalation, and an incision was made to expose the temporalis muscle.…”

“…Mice were randomly allocated into stroke and sham experimental groups. This stroke model creates a large infarct comprising approximately 25% of the stroked hemisphere, has little variability, and excellent long-term survivability (Doyle et al, 2012). Hypoxia is necessary with this model because C57BL/6 mice that undergo DMCAO without hypoxia have significantly smaller infarcts (Doyle et al, 2012).…”

“…This stroke model creates a large infarct comprising approximately 25% of the stroked hemisphere, has little variability, and excellent long-term survivability (Doyle et al, 2012). Hypoxia is necessary with this model because C57BL/6 mice that undergo DMCAO without hypoxia have significantly smaller infarcts (Doyle et al, 2012). BALB/c mice underwent DMCAO without hypoxia, as previously described (Doyle et al, 2012; Nguyen et al, 2016).…”

“…Hypoxia is necessary with this model because C57BL/6 mice that undergo DMCAO without hypoxia have significantly smaller infarcts (Doyle et al, 2012). BALB/c mice underwent DMCAO without hypoxia, as previously described (Doyle et al, 2012; Nguyen et al, 2016). DMCAO by itself generates an infarct in BALB/c mice that is equivalent in size and location to the infarct generated by DH stroke in C57BL/6 mice (Doyle et al, 2012).…”