An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade

Abstract

Stroke is one of the leading causes of death worldwide and the main reason for long-term disability. An appropriate animal model of stroke is urgently required for understanding the exact pathophysiological mechanism of stroke and testing any new therapeutic regimen. Our work aimed to establish a canine stroke model occluding the middle cerebral artery (MCA) and blocking the ipsilateral internal carotid artery (ICA), and to assess the infarct lesions by magnetic resonance imaging. The stroke model was generated by injecting two autologous clots into each MCA, followed by 2-h ipsilateral ICA blockade (ilICAB) using a catheter in 15 healthy adult beagles. Outcome measurements included 24-h and 7-day postocclusion T2-weighted imaging (T2WI)-based infarct volume calculation. In addition, pial collateral score, canine neurobehavioral score and histopathologic results were documented. Out of 15 dogs, 12 with successful MCA occlusion (MCAO) and ilICAB survived 7 days without complications or casualties and MCA were reperfused at 7 days after occlusion. High signal intensity in the basal ganglia and cerebral cortex on T2WI was initially observed in each dog at 6 h after the procedure. The mean percentage hemispherical infarct volume corrected for edema in all dogs on T2WI at 24 h after occlusion was 12.99 ± 1.57%, and the degree of variability was 12.08%. The infarct volumes at 24 h after occlusion correlated with pial collateral scores and canine neurobehavioral scores well. This canine stroke model with combined MCAO and ilICAB reported here were proven to be highly feasible and reproducible.

Endovascular model of ischemic stroke in swine guided by real-time MRI

“…Jahan et al 29 did not evaluate whether the procedure results in ischemia, but they used this model to demonstrate pharmacological thrombolysis using plasmin delivered intraarterially. In dogs with much larger arteries there is more flexibility in navigating catheter and two routes for occluding canine MCA were reported with approach via internal carotid artery 32 or via vertebral artery (VA) 33 . Stroke volume in dogs with ICA emboli injection varies depending on clot size and was the largest in group with clot 1.4 mm/1.7 mm combined with additional ipsilateral ICA transient occlusion (4173.23 ± 603.22 mm 3 ) 14,32 .…”

High b value DWI in evaluation of the hyperacute cerebral ischemia at 3T: A comparative study in an embolic canine stroke model

“…A total of 12 male beagles (13–15 kg; Laboratory Animal Center of Nanjing Medical University) were anesthetized by intravenous injection with 3 ml/kg pentobarbital (Pentobarbital Sodium Salt; Chemical Reagent Company, Shanghai, China). Detailed procedures were described in our previous studies ( 18 – 20 ). In brief, two autologous clots (1.4 and 1.7 mm in diameter and 5 mm in length) were injected into the left middle cerebral artery (MCA).…”

“…The aim of the present study was to evaluate the temporal evolution of rDWI and rADC in three different b values, and further compare their diagnostic performances in identifying the onset time of acute ischemic stroke, based on an embolic canine model with clear onset time ( 18 , 19 ).…”

Validity of a neurological scoring system for canine X-linked myotubular myopathy

“…Clinical rating scores and neurological assessment scores of large animal research models have been reported for gene therapy in feline models of the GM1 and GM2 gangliosidoses, 13,14 canine models of Duschenne muscular dystrophy, 15 and in rabbit and canine stroke models. [16][17][18] In the current project, we hypothesize that the neurological assessment score developed for the XLMTM dog model correlates with genotype and established measures of disease severity, such as hindlimb strength. We also hypothesize that scoring is reliable when performed by an independent observer.…”