Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability

Abstract

Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, obesity and diabetes. Accordingly, when evaluating therapies for stroke in animals, it is important to select a model with excellent face validity. Ischemic stroke accounts for 80% of all strokes, and the majority of these occur in the territory of the middle cerebral artery (MCA), often inducing infarcts that affect the sensorimotor cortex, causing persistent plegia or paresis on the contralateral side of the body. We demonstrate in this video a method for producing ischemic stroke in elderly rats, which causes sustained sensorimotor disability and substantial cortical infarcts. Specifically, we induce permanent distal middle cerebral artery occlusion (MCAO) in elderly female rats by using diathermy forceps to occlude a short segment of this artery. The carotid artery on the ipsilateral side to the lesion was then permanently occluded and the contralateral carotid artery was transiently occluded for 60 min. We measure the infarct size using structural T2-weighted magnetic resonance imaging (MRI) at 24 hr and 8 weeks after stroke. In this study, the mean infarct volume was 4.5% ± 2.0% (standard deviation) of the ipsilateral hemisphere at 24 hr (corrected for brain swelling using Gerriet's equation, n = 5). This model is feasible and clinically relevant as it permits the induction of sustained sensorimotor deficits, which is important for the elucidation of pathophysiological mechanisms and novel treatments.

The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

“… 175 To generate more consistent infarcts, permanent distal MCA occlusion can be combined with tandem CCA occlusion in rats. 79 Surgeons should start with a short CCA occlusion time (e.g. 30 min) to see whether adequate lesion volumes (and/or required behavioural deficits) are obtained and only then increase CCA occlusion if necessary.…”

Development of a Modified Surgical Technique for Simulating Ischemic Cerebral Cortex Injury in Rats

“…Among these methods, craniotomy is a common method, that has the advantage of allowing direct visualization of MCA through the surgical field (9). After the MCA has been exposed, it can be occluded by coagulation, transection, ligation or clips (7).…”

Subcutaneous Neurotrophin-3 infusion induces corticospinal neuroplasticity and improvements in dexterity and walking in elderly rats after large cortical stroke

“…Sprouting was frequently observed at the midline, at distance 1, distance 2 and from the ventral corticospinal tract. Increased sprouting at distance 2 indicates that more corticospinal tract axons extended into the territory of the forelimb motor neuron pools which are located in lateral and ventrolateral grey matter ( Figure 3) 28,29 .…”

“…Peripherally administered neurotrophins accumulate in sensory ganglia where they can cause gene transcription, axon growth of primary afferents, and synapse strengthening within locomotor circuits 8,[22][23][24][25][26][27] . Because >90% of strokes occur in people older than 65 with comorbidities including carotid arterial stenosis 28 , we evaluated the effectiveness of NT-3 in elderly rats with large cortical strokes caused by distal middle cerebral artery occlusion and common carotid occlusion 29 . We chose to deliver our therapy 24 hours after cortical ischemia, because most stroke victims are admitted and diagnosed by this time 1,30 .…”