Lourbopoulos Athanasios, Mamrak Uta, Roth Stefan, Balbi Matilde, Shrouder Joshua, Liesz Arthur, Hellal Farida, Plesnila Nikolaus
1 Laboratory of Experimental Stroke Research, Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center, Munich, Germany.
2 Munich Cluster for Systems Neurology (Synergy), LMU Munich, Munich, Germany.
J Cereb Blood Flow Metab. 2017 Jun;37(6):2084-2097. doi: 10.1177/0271678X16660986. Epub 2016 Jan 1.
Experimental stroke models producing clinically relevant functional deficits are often associated with high mortality. Because the mechanisms that underlie post-stroke mortality are largely unknown, results obtained using these models are often difficult to interpret, thereby limiting their translational potential. Given that specific forms of post-stroke care reduce mortality in patients, we hypothesized that inadequate food and water intake may underlie mortality following experimental stroke. C57BL/6 mice were subjected to 1 h of intraluminal filament middle cerebral artery occlusion. Nutritional support beginning on the second day after filament middle cerebral artery occlusion reduced the 14-day mortality rate from 59% to 15%. The surviving mice in the post-stroke support group had the same infarct size as non-surviving control mice, suggesting that post-stroke care was not neuroprotective and that inadequate food and/or water intake are the main reasons for filament middle cerebral artery occlusion-induced mortality. This notion was supported by the presence of significant hypoglycemia, ketonemia, and dehydration in control mice. Taken together, these data suggest that post-filament middle cerebral artery occlusion mortality in mice is not primarily caused by ischemic brain damage, but secondarily by inadequate food and/or water intake. Thus, providing nutritional support following filament middle cerebral artery occlusion greatly minimizes mortality bias and allows the study of long-term morphological and functional sequelae of stroke in mice.
产生具有临床相关性功能缺陷的实验性中风模型往往与高死亡率相关。由于中风后死亡率的潜在机制很大程度上未知，使用这些模型获得的结果通常难以解释，从而限制了它们的转化潜力。鉴于特定形式的中风后护理可降低患者死亡率，我们推测食物和水摄入不足可能是实验性中风后死亡率的潜在原因。将C57BL/6小鼠进行1小时的腔内细丝大脑中动脉闭塞。在细丝大脑中动脉闭塞后第二天开始的营养支持将14天死亡率从59%降至15%。中风后支持组中存活的小鼠与未存活的对照小鼠梗死面积相同，这表明中风后护理没有神经保护作用，食物和/或水摄入不足是细丝大脑中动脉闭塞诱导死亡率的主要原因。对照小鼠中存在显著低血糖、酮血症和脱水支持了这一观点。综上所述，这些数据表明小鼠细丝大脑中动脉闭塞后死亡率并非主要由缺血性脑损伤引起，而是继发于食物和/或水摄入不足。因此，在细丝大脑中动脉闭塞后提供营养支持可极大地减少死亡率偏差，并允许研究小鼠中风的长期形态和功能后遗症。
