Endovascular ischemic stroke models of adult rhesus monkeys: a comparison of two endovascular methods

Abstract

To further investigate and improve upon current stroke models in nonhuman primates, infarct size, neurologic function and survival were evaluated in two endovascular ischemic models in sixteen rhesus monkeys. The first method utilized a micro-catheter or an inflatable balloon to occlude the M1 segment in six monkeys. In the second model, an autologous clot was injected via a micro-catheter into the M1 segment in ten monkeys. MRI scanning was performed on all monkeys both at baseline and 3 hours after the onset of ischemia. Spetzler neurologic functions were assessed post-operatively, and selective perfusion deficits were confirmed by DSA and MRI in all monkeys. Animals undergoing micro-catheter or balloon occlusion demonstrated more profound hemiparesis, larger infarct sizes, lower Spetzler neurologic scores and increased mortality compared to the thrombus occlusion group. In animals injected with the clot, there was no evidence of dissolution, and the thrombus was either near the injection site (M1) or flushed into the superior division of the MCA (M2). All animals survived the M2 occlusion. M1 occlusion with thrombus generated 50% mortality. This study highlighted clinically important differences in these two models, providing a platform for further study of a translational thromboembolic model of acute ischemic stroke.

Figure 1. Physiological parameters of animal models subjected to endovascular inducement.

(a) Systolic blood pressure, (b) diastolic blood pressure and (d) rectal temperatures were increased at 3 h after the onset of ischemia in the micro-catheter group comparing to baseline values. No significant difference was found for (c) heart rate, (e) SaO₂, (f) (pCO₂), (g) haematocrit, and (h) glucose when adopting the two endovascular methods. *P < 0.05. SaO₂: oxygen saturation; pCO₂: partial pressure of carbon dioxide.

Figure 2. Images from an animal undergoing ischemia through the micro-catheter method.

(a) A lateral pre-occlusion angiogram demonstrated normal MCA, its divisions and the position of the micro-catheter. (b) A lateral post-occlusion angiogram illustrated the perfusion deficit in the M1 main trunk. (c) There was a prolonged T2, indicating early vaso-genic edema. (d) Diffuse hyper-intensity on DWI scans indicated ischemic lesions. A: anterior; P: posterior; R: right; L: left.

Figure 3. Comparison of infarct size, midline shift, Spetzler Scores and operation duration between the micro-catheter and the thrombus group.

(a) The micro-catheter group had larger infarct sizes both in DWI and T2 at 3 h following the ischemia. (b) The micro-catheter group had an increased midline shift compared to the thrombus group. (c) The micro-catheter group had decreased Spetzler scores both at 12 hours and 24 hours when compared to the thrombus group. (d) The micro-catheter group had a shorter operation duration compared to the thrombus group. *P < 0.05.

Figure 4. Images from a M1 model of ischemic stroke with an autologous clot.

(a) A lateral pre-occlusion angiogram demonstrated normal MCA, its divisions and the position of the micro-catheter. (b) A lateral post-occlusion angiogram illustrated the perfusion deficit in the M1 divisions. (c) Local hyper-intensity was obvious in T2 scans. (d) Local hyper-intensity on DWI scans indicated ischemic lesions. A: anterior; P: posterior; R: right; L: left.

Figure 5. Images from a M2 model of ischemic stroke with an autologous clot.

(a) A lateral pre-occlusion angiogram demonstrated normal MCA, its divisions and the predominant superior division. (b) A lateral post-occlusion angiogram illustrated the perfusion deficit in the superior division. (c) There was also an abnormal T2 scans indicating ischemic lesions. (d) Local hyper-intensity on DWI scans indicated ischemic stroke. A: anterior; P: posterior; R: right; L: left.

Figure 6. Perfusion deficit in the thrombus group.

The perfusion deficit was more obvious based on CBF (a) and MTT (c) when M1 was blocked, compared with the perfusion deficit according to CBF (b) and MTT (d) when M2 was occluded. A: anterior; P: posterior; R: right; L: left.

Figure 7. Analysis of possible factors related to the survival of models.

(a) Dead animals had larger infarct sizes both in DWI and T2 at 3 h following the ischemia. (b) Dead monkeys had an increased midline shift compared to alive ones. (c) Dead animals had decreased Spetzler scores both at 12 hours and 24 hours when compared to living ones. (d) Dead animals had a higher systolic pressure at 3 hours compared to living ones. *P < 0.05.