Transarterial Regional Brain Hypothermia Inhibits Acute Aquaporin-4 Surge and Sequential Microvascular Events in Ischemia/Reperfusion Injury

Abstract

AQP4, aquaporin-4BBB, blood-brain barrierIba1, ionized calcium-binding adapter molecule 1ICA, internal carotid arteryICAM-1, intracellular adhesion molecule-1I/R, ischemia/reperfusionMCAO, middle cerebral artery occlusionMMP-9, matrix metalloproteinase-9.

Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

“…The present study demonstrated that transarterial regional hypothermia exerts robust neuroprotective effects in the pMCAO with tCHP model, as well as the typical tMCAO model, as reported previously (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Kurisu et al, 2015;Luan et al, 2004;Zhao et al, 2009). This therapy significantly improved neurological deficits and decreased infarct/edema volumes.…”

“…Consistent with previous findings (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Luan et al, 2004;Zhao et al, 2009), we also clarified that transarterial regional hypothermia exerts strong neuroprotective effects on ischemia-reperfusion (I/R) injury (Kurisu et al, 2015). However, the effects of this therapy have only been examined in a typical ischemic stroke model, the transient middle cerebral artery occlusion (tMCAO) model (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Kurisu et al, 2015;Luan et al, 2004;Zhao et al, 2009), which is a complete reperfusion model (Fluri et al, 2015;Takahashi et al, 2012;Zhao and Steinberg, 2011). The effects of this therapy have not yet been investigated in other ischemic stroke models, even though ischemic stroke in humans is extremely diverse in its pattern of occlusion and reperfusion in actual clinical settings.…”

“…Therefore, transarterial regional hypothermia is strongly expected to become a novel attractive treatment for acute ischemic stroke because of its rapid cooling action and fewer systemic side effects (Dumitrascu et al, 2016;Esposito et al, 2014;Kurisu et al, 2015). Consistent with previous findings (Chen et al, 2013;Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Luan et al, 2004;Zhao et al, 2009), we also clarified that transarterial regional hypothermia exerts strong neuroprotective effects on ischemia-reperfusion (I/R) injury (Kurisu et al, 2015).…”

“…Transarterial regional hypothermia shows rapid and selective brain cooling in the model of pMCAO with tCHP as well as in the tMCAO model (Ding et al, 2003;Ding et al, 2004a;Ding et al, 2004b;Kurisu et al, 2015;Luan et al, 2004;Zhao et al, 2009). A comparison of the depth and duration of the cooling effect revealed that it was weaker in the model of pMCAO with tCHP than in the tMCAO model, but still mediated significant temperature lowering (2 to 3°C for 15 minutes).…”

“…We speculate that transarterial regional hypothermia may utilize a different mechanism to that of general hypothermia in order to mediate neuroprotection. Since CS is directly infused into the vascular system, transarterial regional hypothermia may have a more direct and intensive cooling effect on the microvascular endothelium and its surroundings (Kurisu et al, 2015). This cooling effect may be important for the therapeutic mechanism, resulting in the difference observed.…”