Stroke — Animal Models & Recovery Testing

MCAO (intraluminal filament) is the gold standard for clinically relevant focal ischemia — it produces large cortical-striatal infarcts mimicking human large-vessel stroke. Photothrombotic stroke provides precise, reproducible cortical lesions ideal for plasticity and rehabilitation research. Endothelin-1 allows targeted ischemia at specific brain regions. Global ischemia (BCCAO) models cardiac arrest outcomes with selective hippocampal damage. Choose based on whether you need motor outcomes (focal models) or cognitive outcomes (global ischemia).

A silicon-coated nylon monofilament is inserted through the external carotid artery, advanced through the internal carotid artery, and positioned at the origin of the middle cerebral artery to block blood flow. For transient ischemia, the filament is withdrawn after 60–90 minutes; for permanent ischemia, it is left in place. Laser Doppler flowmetry over the MCA territory confirms successful occlusion (>70% reduction in cerebral blood flow). Infarction develops in the MCA territory affecting striatum and lateral cortex.

Motor assessment: rotarod (coordination and balance), balance beam (foot slips and traversal time), grip strength (contralateral forelimb weakness), and gait analysis (stride asymmetry). Cognitive assessment: Morris water maze and Barnes maze (spatial learning), Y-maze spontaneous alternation (working memory), and novel object recognition (recognition memory). Always include open field as a locomotor control. For focal ischemia, test motor outcomes acutely (24–72 hours) and longitudinally (1–4 weeks); delay cognitive testing until motor function partially recovers.

Photothrombotic stroke uses the photosensitive dye rose bengal (injected IV at 10–30 mg/kg) combined with focused illumination through the intact skull. Light activation of rose bengal generates singlet oxygen that damages vascular endothelium, triggering platelet aggregation and localized thrombosis. The result is a sharply demarcated cortical infarct whose size and location are controlled by the illumination spot diameter and position. It is minimally invasive (no craniotomy), highly reproducible, and has low mortality (~5%).

Hippocampal CA1 pyramidal neurons are selectively vulnerable to ischemia due to high expression of glutamate receptors (especially NMDA receptors), high metabolic demand, limited collateral blood supply, and slower post-ischemic recovery of protein synthesis. During global ischemia, excitotoxic glutamate release causes calcium overload specifically in CA1 neurons, triggering delayed cell death 2–4 days after reperfusion. This selective vulnerability is why cardiac arrest survivors often present with memory impairment despite intact motor and sensory function.

For focal ischemia (MCAO, photothrombotic): wait 7–14 days before spatial learning tasks (MWM, Barnes maze) to allow motor recovery — swim impairment confounds water maze performance. Novel object recognition can be tested earlier (3–7 days) because it has low motor demand. For global ischemia (BCCAO): motor function is largely preserved, so cognitive testing can begin at 7 days when CA1 neuronal death has peaked. Y-maze spontaneous alternation at 7 days provides a quick cognitive screen before committing to a full MWM protocol.