TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10 min or shorter

Abstract

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA.

Animal models of transient ischemic attack: a review

“…However, the basic research on TIA is limited, and methods are still being developed. According to the definition of TIA, the establishment of a successful and reliable TIA animal model should follow three criteria [20,35]: (1) objective evidence of cerebral arteries occlusion and reperfusion, (2) no permanent neurological deficit, (3) no acute cerebral infarction. The importance of the first criterion is to confirm the occurrence of transient cerebral ischemia by monitoring CBF and to promptly exclude the animals with inadequate occlusion or inappropriate reperfusion.…”

“…It is worth noting that the infarct thresholds (the minimum duration of ischemia that can cause cerebral infarction) vary in different animals used in the suture method of TIA. The mechanism for this variation is still unclear and may be caused by many factors, including differences in the composition of the circle of Willis, the distribution of gray and white matter, neuron density and other neuromorphological features [20]. Furthermore, because of individual differences in the formation of collateral circulation, the same strain may present different infarct thresholds.…”

Dl-3-N-Butylphthalide Promotes Angiogenesis in an Optimized Model of Transient Ischemic Attack in C57BL/6 Mice

“…One reason for this is the lack of an appropriate and available animal model, making it difficult to further explore the pathology, mechanisms and potential targeted treatments of TIA. In this study, we utilized the suture MCAO method and followed the three established criteria of TIA models ( Pedrono et al, 2010 ; Durukan et al, 2017 ) to evaluate the outcomes of 7–10 min of ischemia in C57BL/6 mice to establish an optimal TIA model. The criteria are as follows: 1) objective evidence of ischemia and reperfusion, primarily relying on CBF monitoring to confirm adequate occlusion and reperfusion; 2) no permanent neurological deficit; and 3) no acute cerebral infarction.…”

“…The intraluminal suture middle cerebral artery occlusion (MCAO) method is minimally invasive and easy to perform, with the ability to precisely control the ischemia-reperfusion process, and thus is a preferable method for TIA modeling. Based on this method, Durukan ( Durukan et al, 2017 ) and Pedrono ( Pedrono et al, 2010 ) established TIA models in Wistar rats and NMRI mice, respectively, by controlling the duration of ischemia. They found that in both species, no cerebral infarction confirmed by MRI occurred when the occlusion lasted no more than 10 min.…”

“…Here, we aim to develop a TIA model in C57BL/6 mice by exploring the ischemia duration based on the intraluminal suture MCAO method. To realize the relevance to clinical TIA, three criteria of TIA model were proposed ( Pedrono et al, 2010 ; Durukan et al, 2017 ): 1) objective evidence of ischemia and reperfusion, 2) no permanent neurological deficit, and 3) no acute cerebral infarction. In this study, laser speckle contrast imaging (LSCI) was used during surgery to evaluate cerebral arteries occlusion and reperfusion.…”