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Because the clinical studies of neuroprotective drugs ended in failure, the Stroke Treatment Academy Industry Roundtable recommended the use of non-human primates for preclinical research on stroke. Non-human primates are the bridge between basic experiment and clinical research, and the experimental results are of great reference value. However, non-human primate stroke models have a variety of neurological deficits and behavioral evaluation methods, and the scoring methods also have their own emphases. It is easy to have differences in the evaluation, or there are deficiencies in the scale itself, resulting in inaccurate scoring, which directly affects the experimental results and the implementation of subsequent research. This article summarizes the neurological deficits and behavioral evaluation methods of non-human primate stroke model.
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Objective To investigate the neuroprotective effect and its mechanism of local hypothermia combined with nicotinamide phosphoribosyltransferase (NAMPT) on cerebral ischemia-reperfusion injury in rats.Methods Fifty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,NAMPT group,local hypothermia group,and combined treatment group (NAMPT + local hypothermia).A rat model of local cerebral ischemia-reperfusion was induced by suture method.Infarct volume and cerebral edema volume were assessed by 2,3,5-triphenyltetrazolium chloride staining after 2 h cerebral ischemia and 24 h reperfusion in rats.Evans blue staining was used to assess the extent of blood-brain barrier damage,and a 12-point scale was used to assess neurological deficits.Results The infarct volume in the local hypothermia group,NAMPT group,and combination treatment group was significantly lower than that in the model group (all P ＜0.05).The infarct volume in the combination treatment group was significantly lower than that in the NAMPT group (P ＜0.05).The infarct volume in the combination treatment group was lower than that in the local hypothermia group,but it did not reach statistical significance.The neurological function scores of the local hypothermia group,NAMPT group,and combination treatment group were significantly lower than those of the model group (all P ＜0.05).The score of the combined treatment group was significantly lower than that of the NAMPT group and the local hypothermia group (all P＜0.05).Evans blue leakage in the local hypothermia group,NAMPT group,and combination treatment group was lower than that in the model group (all P ＜0.05),but the differences between each treatment group were not statistically significant.Conclusion NAMPT and local hypothermia combination therapy showed better neuroprotective effects on cerebral ischemia-reperfusion injury,suggesting that the combination therapy had clinical transformation prospects.
ABSTRACT
The Stroke Therapy Academic Industry Roundtable(STAIR)committee has suggested that nonhuman primates(NHPs)should be used for preclinical stroke studies owing to previous translational failures. Ischemia induced by endovascular method closely mimics thromboembolic or thrombotic cerebrovascular occlusion in patients. This method also shows potential for endovascular treatment. This review provides a detailed summary of NHP models using endovascular method,including advantages and disadvantages,and potential applications. Additionally,we also provide further analysis based on different kinds of emboli,infract size,and abnormal hemodynamics. Selection of the optimum model will pave the way for translational research.
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Objective To examine the nonhuman primate(NHP)model of acute cerebral infarction thrombus-thrombolysis using multi-parameter high-field magnetic resonance imaging(MRI). Methods Altogether, 8 adult male rhesus monkeys aged 8.2(± 1.2)years old and weighing 9.4(± 1.0)kg were randomized into an infarction group(n=4)and thrombolysis group(n =4). Middle cerebral artery occlusion(MCAO)was induced with a clot in the M1 segment. Monkeys in the thrombolysis group were treated with the recombinant tissue plasminogen activator, rt-PA, while those in the infarction group were treated with 0.9% NaCl only. T2 weighted imaging(T2WI), T2-weighted-fluid-attenuated inversion recovery(T2-FLAIR), time-of-flight magnetic resonance angiography(TOF-MRA), and diffusion-weighted imaging(DWI)were used to examine all monkeys at 4 and 24 h after onset of ischemia. Results The rhesus monkey thrombus-thrombolysis model was successfully established. MRA showed that the middle cerebral artery(MCA) was not recanalized in the infarction group, but was recanalized in the thrombolysis group. T2WI sequence showed an increase in infarction volume(12 027 ± 5507 mm3)in the infarction group compared with the thrombolysis group(4910 ± 2764 mm3). DWI sequence showed an increase in infarction volume(9498 ± 5226 mm3)in the infarction group and thrombolysis group(4854 ± 1792 mm3). Both T2WI and DWI sequences showed no significant difference in infarction volume at 4 h between the two groups, while infarction volume in the thrombolysis group at 24 h was significantly lower compared with the infarction group. The increase in infarction volume was significantly lower in the thrombolysis group compared with the infarction group. Conclusions MRI sequences can be used to successfully evaluate recanalization and infarct changes in the thrombus-thrombolysis model in rhesus monkeys.