Direct Experimental Occlusion of the Distal Middle Cerebral Artery Induces High Reproducibility of Brain Ischemia in Mice

Abstract

Several investigators have used murine models to investigate the pathophysiology of brain ischemia. The focal ischemic model is a closer approximation to human stroke which includes a necrotic core, penumbra, and undamaged tissue. Occlusion of a unilateral artery, especially the middle cerebral artery (MCA), is performed in this model, but collateral circulation often induces variation of ischemic lesions both qualitatively and quantitatively. It is likely that the more proximal the artery which is unilaterally occluded is, the more inconsistent the outcomes. The present study was designed to examine the reproducibility of infarct lesion by distal or proximal artery occlusion. Direct occlusion of the distal MCA was performed and compared with unilateral common carotid artery occlusion (CCAO) in C57BL/6 mice. Direct MCA occlusion (MCAO) consistently induced ischemic lesions in cortical areas. All model animals (n=14) survived 24 h after occlusion, and exhibited a maximum infarct volume (20.0 ± 5.0%). In contrast, permanent and transient unilateral CCAO models had mortality rates of 62.5 and 25.0%, and showed severe to absent lesions with the infarct volumes of 29.0 ± 20.8 and 33.2 ± 24.2%, respectively. In conclusion, distal MCAO produces high reproducibility of ischemic insults and survivability compared to unilateral CCAO. Thus, distal MCAO is a useful method for the focal ischemic model.

In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

“…dMCAO was used as an experimental model of cortical ischemia (Kuraoka et al, 2009;Pena-Philippides et al, 2014). This model produces an infarct in the frontal and parietal cortex, which over time progresses into adjacent temporal, frontal, and cingulate cortex.…”

“…In addition, dMCAO induces mostly cortical ischemia and thus represents a convenient model for in vivo imaging, which is limited by its depth penetration capacities. dMCAO was performed on 2-month-old male C57BL/6 mice (Jones et al, 2008;Kuraoka et al, 2009). The mice were anesthetized using isoflurane gas (induction dosage 2-3%; maintenance dosage 1.5-2%) and a mixture of O 2 :N 2 O gases in the ratio 2:1 delivered during the surgery.…”

“…The mice were anesthetized using isoflurane gas (induction dosage 2-3%; maintenance dosage 1.5-2%) and a mixture of O 2 :N 2 O gases in the ratio 2:1 delivered during the surgery. The middle cerebral artery (MCA) was exposed via a transtemporal approach (Jones et al, 2008;Kuraoka et al, 2009). A small burr hole (located 1 mm rostral to the fusion of zygoma and squamosal bone and 3 mm ventral to the parietal bone) was made on the left side of the skull surface and the MCA was coagulated with low-heat electrocautery (Bovie Medical).…”

Intravenously Delivered Allogeneic Mesenchymal Stem Cells Bidirectionally Regulate Inflammation and Induce Neurotrophic Effects in Distal Middle Cerebral Artery Occlusion Rats Within the First 7 Days After Stroke

“…Permanent occlusion was induced by electrocauterization of the distal portion of the MCA in conjunction with ligation of both common carotid arteries for 30 min [23, 24]. During surgery, body temperature was maintained at 37°C using a heating pad.…”

“…To minimize the error introduced by edema, which distorts and enlarges the infarcted tissue and surrounding white matter, infarct areas for each section were calculated by subtracting the area of intact tissue in the ipsilateral hemisphere from the corresponding area of the contralateral hemisphere. Infarct volumes were calculated by multiplying the summarized infarct areas (all 6 sections) by the interval distance betweenthe sections (2 mm in this experiment) [27]. …”