Background and Purpose- Induction of hypothermia as a stroke therapy has been limited by logistical challenges. This study was designed to determine the hypothermic and neuroprotective efficacy of infusing cold saline directly into the internal jugular (IJ) vein and compare the effects of IJ hypothermia to those achieved by intracarotid artery hypothermia in an ischemic stroke model. Methods- The right middle cerebral artery was occluded in rats using an intraluminal filament. Immediately following reperfusion, hypothermia was achieved by infusing isotonic saline through microcatheter into the right IJ or right intracarotid over 30 minutes. Infarct sizes, neurological deficits, blood-brain barrier damage, edema volume, blood-brain barrier associated molecules (MMP-9 [matrix metallopeptidase 9] and AQP-4 [aquaporin 4]), and apoptosis-associated proteins (Bcl-2 and cleaved Caspase-3) were measured. Results- We found that both IJ- and intracarotid-based infusion cooled the brain robustly with a minimal effect on rectal temperatures. This brain cooling led to significantly reduced infarct volumes at 24 hours after reperfusion, as well as decreased expression of the proapoptotic protein cleaved Caspase-3 and increased expression of the antiapoptotic protein Bcl-2. Intracarotid and IJ cooling also aided in blood-brain barrier maintenance, as shown by decreased edema volumes, reduced Evans Blue leakage, and decreased expression of edema-facilitating proteins (MMP-9 and AQP-4). Both cooling methods then translated to preserved neurological function as determined by multiple functional tests over a 28-day observation period. Most importantly, the cooling and neuroprotective efficacy of IJ cooling was comparable to intracarotid cooling by almost every metric evaluated. Conclusions- Compared with intracarotid infusion, IJ infusion conferred a similar degree of hypothermia and neuroprotection following ischemic stroke. Given the ease of establishing vascular access via the internal jugular vein and the powerful neuroprotection that hypothermia provides, IJ brain cooling could be used as a promising hypothermia-induction modality going forward.

中文翻译：

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颈动脉内冷却和对缺血性卒中的神经保护作用的低温治疗的新的血管内方法。

背景和目的-将低温作为中风疗法的诱导受到后勤挑战的限制。本研究旨在确定将冷盐水直接注入颈内（IJ）静脉的低温和神经保护功效，并在缺血性卒中模型中比较IJ低温疗法与颈动脉内低温疗法所达到的效果。方法-使用腔内灯丝将大鼠右大脑中动脉闭塞。再灌注后，立即通过在30分钟内通过微导管将等渗盐水注入右IJ或右颈内动脉来实现体温过低。梗塞面积，神经功能缺损，血脑屏障损害，水肿体积，血脑屏障相关分子（MMP-9 [基质金属肽酶9]和AQP-4 [水通道蛋白4]），测定细胞凋亡相关蛋白（Bcl-2和裂解的Caspase-3）。结果-我们发现，基于IJ和基于颈动脉的输注均能使大脑强大地冷却，而对直肠温度的影响却很小。这种脑部冷却导致再灌注后24小时的梗塞体积显着减少，以及促凋亡蛋白裂解的Caspase-3的表达降低和抗凋亡蛋白Bcl-2的表达增加。颈动脉内和IJ冷却还有助于维持血脑屏障，如水肿量减少，伊文思蓝渗漏减少和水肿促进蛋白（MMP-9和AQP-4）的表达减少所表明的。然后，在28天的观察期内，两种冷却方法均转换为保留的神经功能，这是通过多项功能测试确定的。最重要的是，在几乎所有评估指标上，IJ降温的降温和神经保护功效均与颈内降温相当。结论-与颈内输注相比，IJ输注在缺血性中风后具有相似程度的体温降低和神经保护作用。鉴于通过颈内静脉建立血管通路的简便性和体温过低提供的强大神经保护作用，IJ脑冷却可以用作未来有希望的体温过低诱导方式。