Department of Surgical Sciences, Anesthesiology, and Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden.
International Experimental CNS Injury and Repair (IECNSIR), University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 28, SE-75421, Uppsala, Sweden.
Mol Neurobiol. 2018 Jan;55(1):276-285. doi: 10.1007/s12035-017-0740-y.
The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 °C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier.
本研究在大鼠模型中考察了创伤性脑损伤（TBI）发生于寒冷环境是否会加重脑病理和氧化应激。在冷适应大鼠（5°C 每日 3 小时，共 5 周）或在室温下接受 Equithesin 麻醉的动物中，通过在右顶叶大脑皮质（2mm 深，4mm 长）做纵向切口造成 TBI。与室温下相同的 TBI 相比，暴露于寒冷中的大鼠的 TBI 明显增加了脑内的光解萤光素（LCG）、鲁米诺（LUM）和丙二醛（MDA），并显著降低了谷胱甘肽（GTH）。与室温相比，受伤后冷暴露大鼠的血脑屏障（BBB）对放射性碘和 Evans 蓝白蛋白的通透性、水肿形成和神经元损伤的程度和强度也加剧。在冷暴露组中，伤后 6 和 8 小时给予 H-290/51（50mg/kg）的纳米输送显著阻止了脑病理和氧化应激，而在室温下 TBI 后，正常给予 H-290/51 具有神经保护作用。这些观察结果首次表明：（i）寒冷加重了 TBI 的病理生理学，可能是由于氧化应激的产生增强；（ii）在这种情况下，抗氧化剂化合物的纳米输送具有更好的神经保护作用，这是以前没有报道过的。
