Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical and histopathological findings

Abstract

The aim of the present study was to assess the clinical and histopathological findings in a canine model of ischemic stroke. Cerebral ischemic stroke was induced by middle cerebral artery occlusion in four healthy beagle dogs using silicone plugs. They showed neurological signs of forebrain dysfunction such as reduced responsiveness, head turning, circling, postural reaction deficits, perceptual deficits, and hemianopsia. These signs gradually regressed within 4 weeks without therapy. On magnetic resonance imaging, T2 hyperintensity and T1 hypointensity were found in the cerebral cortex and basal ganglia. These lesions were well-defined and sharply demarcated from adjacent brain parenchyma with a homogenous appearance. No abnormalities of the cerebrospinal fluid were observed. At necropsy, atrophic and necrotic lesions were observed in the cerebral cortex. The cerebral cortex, basal ganglia, and thalamus were partially unstained with triphenyl- tetrazolium chloride. Histopathologically, typical features of infarction were identified in cortical and thalamic lesions. This study demonstrates that our canine model resembles the conditions of real stroke patients.

Fig. 1

Transverse (A and B) and dorsal (C and D) T1-weighted and T2-weighted MR images of the brain in an experimentally embolized dog (ID 2). Hypointense (A and C) and hyperintense (B and D) lesions were found in lateral cortex (arrows) and caudate nucleus (arrow heads). In T2-weighted image, the well defined lesion was sharply demarcated from adjacent brain parenchyma with a homogenous appearance. Swelling, midline shift, and suppressed left lateral ventricle and thalamus by mass effect were identified in all images.

Fig. 2

The ventral (A) and lateral (B) surface of the brain (ID 2) 4 months after MCAO by a silicone embolus exhibits remarkable atrophy and necrosis (arrows) in the affected lateral cortex.

Fig. 3

Coronal section of the brain (ID 2) after TTC staining demonstrate unstained lesion on thalamus (arrow) and atrophic changes (arrow heads) on the left lateral cortex.

Fig. 4

Microscopic features of the brain in an experimentally embolized dog (ID 2). (A) Thalamic lesion. Necrotic neurons (arrows), nuclear pyknosis, eosinophilia of the cytoplasm, and karyolysis were prominent. H&E stain, ×400. (B) Cortex lesion. Loss of tissue cohesion, infiltration by leukocytes (especially polymorphonuclear leukocytes), congestion of small parenchymal blood vessels (arrow heads), and angioblastic proliferation were observed. H&E stain, ×100.