Preclinical acute ischemic stroke modeling

Abstract

Preclinical ischemic stroke is at the crossroads in search of reliable and robust simulation models as past experiences with their translation from the laboratory to the standard of clinical care have often been disappointing. The efficacy of neuroprotective agents is still elusive, and the use of thrombolytics alone is limited to the narrow time window of presentation from the onset of the deficit. Hence, the focus has shifted to interventional revascularization to salvage the parenchyma at the risk of infarction. As the burden of disease morbidity and mortality is so enormous, neurointerventionalists have adopted a more aggressive approach to mechanical revascularization with the limited approved tools available-the Penumbra and the MERCI retrieval system, and the recently incorporated stent retrievers. In fact, the interventional space is among the fastest growing fields in stroke research today. Assessing treatment efficacy in these scenarios is infinitely complex as the heterogeneity of the cerebrovasculature, physical and mechanical nature of the occlusive embolus and the time of presentation are all confounders in assessing treatment outcomes. As no single thromboembolic model is apt to address all of these questions, an integrated methodology with a combination of both in vitro and in vivo assessment needs to be adopted. This involves clinically relevant thromboembolic analogs in device evaluation in vascular replicas, thromboembolic stroke induction in large animal gyrencephalic ischemic stroke models for thrombolytic, imaging and neuroprotection research and a native cerebrovascular target for evaluation of the safety and efficacy of mechanical thrombectomy devices.

Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

“…Differences in stroke outcomes and the effect of potential neuroprotectants on them, between agyric and gyric brains, have been well discussed previously. 42 Seventh, most data involved young male animals (n ¼ 11 for lesion volume) and few related to aged males, overiectomized females, and none in hormonally intact females. Further experiments in older animals and hormonally intact females are required before the translational potential of progesterone treatment can be predicted.…”

Interventional 4-D C-Arm CT Perfusion Imaging Using Interleaved Scanning and Partial Reconstruction Interpolation

“…Note, there is no minimally invasive stroke model for pigs since the rete mirabile does not permit endovascular access to the anterior cerebrovasculature [29]. Further studies involving animal stroke models or human stroke patients are necessary for the validation of our methods and will be carried out in the future.…”

“…In order to decrease the influence of large vessels we additionally applied a vascular pixel elimination (VPE) similar to the method described in [27]. If the mean CBV value from perfusion CT in a certain square ROI was above the threshold value of 8 ml/100g (this value was suggested in [27] for human data and we assumed it also applies to the data from our in vivo pig studies because of the similarities of the human brain and the pig brain [28], [29]) then the data from this ROI was not used for the correlation analysis.…”

Effectiveness of Mechanical Endovascular Thrombectomy in a Model System of Cerebrovascular Occlusion

“…These cannot be assessed by using in vitro modeling, and consequently preclinical assessment in animal models is still required. 25 …”