College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan, S7N 5C9, Canada.
Curr Neurovasc Res. 2011 Feb;8(1):64-74. doi: 10.2174/156720211794520206.
Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p < 0.027). In the immediate post-surgical period, PEM decreased body temperature to a greater extent than that in well-nourished controls (p = 0.003). The increase in daily temperature fluctuation caused by PEM persisted throughout the 7 day post-surgical period (p < 0.001), and this interacted with the effects of global ischemia on days 8 (p = 0.018) and 11 (p = 0.021). The astrocytic and microglial responses induced at 7 days after global ischemia were not influenced by PEM, but this preliminary analysis needs to be confirmed with a more reliable global ischemia model. In conclusion, exposure to a low protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke victims with coexisting PEM.
合并存在的蛋白质-能量营养不良（PEM），其特征为蛋白质和能量状态均有缺陷，会损害全脑缺血后的功能预后，并与活性神经胶质增生增加有关。由于温度是缺血性损伤后脑损伤的关键决定因素，因此本研究旨在探讨缺血后体温调节的改变是否导致 PEM 诱导的缺血后活性神经胶质增生。雄性 Sprague-Dawley 大鼠（190-280g）分为对照组（18%蛋白质）或 PEM 组（7 天前给予低蛋白饮食，2%蛋白质），然后进行全脑缺血或假手术。通过生物电传感器发射器连续记录核心温度，发现低蛋白饮食组大鼠的体温调节功能迅速受到破坏。在最初的 24 小时内，每日温度波动和平均温度升高，在缺血前 7 天期间一直显著升高（p<0.027）。在手术后即刻，PEM 组的体温下降程度比营养良好的对照组更大（p=0.003）。PEM 引起的每日温度波动增加持续到手术后 7 天（p<0.001），并且这与全脑缺血对第 8 天（p=0.018）和第 11 天（p=0.021）的影响相互作用。全脑缺血后 7 天诱导的星形胶质细胞和小胶质细胞反应不受 PEM 的影响，但这一初步分析需要用更可靠的全脑缺血模型来证实。总之，暴露于低蛋白饮食会迅速损害维持体温调节平衡的能力，而由此产生的 PEM 也会降低对挑战的体温调节能力。由于体温调节是缺血后脑损伤的关键决定因素，这些发现表明，合并存在的 PEM 可能改变中风患者的脑损伤病理生理学。
