Rabbit Small Clot Embolic Model Research Articles

Dose-finding study of phototherapy on stroke outcome in a rabbit model of ischemic stroke

GoalWhile transcranial laser therapy (TLT) has been shown to improve clinical outcome in a preclinical model of ischemic stroke, optimal timing and dosing has yet to be tested adequately. The purpose of this study was to assess clinical stroke outcome in the Rabbit Small Clot Embolic Model (RSCEM) with dose escalating TLT. MethodsWe utilized the rabbit small clot embolic stroke model (RSCEM) using dose-escalating regimens. Behavioral analysis was conducted at 24h post-embolization, allowing for the determination of the effective stroke dose (ES50) or clot amount (mg) that produces neurological deficits in 50% of a group of rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the ES50 compared with the control group. FindingsA significant behavioral benefit was seen at triple TLT of 111mW treatment of 2min at 2h post-embolization (6.47±1.06, n=17; p=0.03), compared with the previously used regimen (3.09±0.51, n=15). ConclusionTLT results in significant behavioral improvement when administered 2h post-embolization. Studies are warranted to evaluate this therapy in combination with thrombolysis.

A novel model of large vessel ischemic stroke in rabbits: microcatheter occlusion of the posterior cerebral artery

Background and purposeThe rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet has limitations. Blind introduction of autologous thrombus often fails to completely occlude a...

Antiplatelet Loading Improves Behavioral Outcome in a Rabbit Model of Stroke

No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model. Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group). There was a significant difference in 3-hour arachidonic acid and ADP (P<0.011); 6-hour collagen and ADP (P<0.01, P<0.01); and 24-hour collagen, arachidonic acid, and ADP (P=0.02, P<0.01, P<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (P=0.02). This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies.

Abstract 3616: A Novel Model of Large Vessel Ischemic Stroke in New Zealand White Rabbits: Microcatheter Occlusion of the Posterior Cerebral Artery

Introduction: The rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet remains with limitations. Blind introduction of autologous thrombus often fails to occlude the target vessel, and when successful, the precise timing of occlusion and revascularization are difficult to control. Studies of cellular biology and neuroimaging of acute reversible cerebral ischemia (i.e., penumbral tissue) would benefit from a rabbit model in which LVO can be reliably induced and easily confirmed, where the time of occlusion and revascularization can be precisely controlled. Hypothesis: We hypothesized that microcatheterization of the posterior cerebral artery (PCA) in New Zealand white rabbits (NZWRs) would result in LVO, with time of revascularization controlled by microcatheter removal. We hypothesized that transient LVO would produce ischemia in subcortical structures supplied by the PCA (e.g., hippocampus), sparing the cortex, with longer duration LVO leading to irreversible cortical ischemia. Methods: Transfemoral 1.5F microcatheterization of the PCA was performed in anesthetized NZWRs using fluoroscopic guidance. LVO was maintained for 30 minutes (n=2), 60 minutes (n=2), 180 minutes (n=2) and 210 minutes (n=1), followed by microcatheter removal and reperfusion. Neuroimaging was obtained 3 hours later with MRI (3T DWI, FLAIR, gradient and perfusion sequences) and CT (64 slice noncontrast and perfusion imaging). Post-mortem histologic analysis of infarct was assessed using triphenyltetrazolium choloride (TTC) stain. Matched DWI and TTC sections were analyzed using ImageJ software. Results: Percent infarct of matched DWI and TTC sections was strongly correlated (r2 = 0.86). Transient LVO of 30-60 minutes resulted in infarction of the ipsilateral hippocampus and thalamus, sparing the cortex, while more prolonged LVO (180-210 minutes) led to cortical infarction as well. Conclusions: Image-guided microcatheter induction of LVO in NZW rabbits can reliably produce time-dependent infarction of cortical and subcortical structures, and thus may be a useful model for the study of penumbral cortical tissue.