Ding Yuchuan, Li Jie, Luan Xiaodong, Lai Qin, McAllister James P, Phillis John W, Clark Justin C, Guthikonda Murali, Diaz Fernando G
Department of Neurological Surgery, Wayne State University School of Medicine, Lande Medical Research Building, Room 48, 550 East Canfield, Detroit, MI 48201, USA.
Neurosurgery. 2004 Apr;54(4):956-64; discussion 964-5. doi: 10.1227/01.neu.0000114513.96704.29.
The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole-body surface cooling, has been limited primarily because of management problems and severe side effects (e.g., pneumonia). The goal of this study was to determine whether local infusion of saline into ischemic territory could induce regional brain cooling and neuroprotection.
A novel procedure was used to block the middle cerebral artery of rats for 3 hours with a hollow filament and locally infuse the middle cerebral artery-supplied territory with 6 ml cold saline (20 degrees C) for 10 minutes before reperfusion.
The cold saline infusion rapidly and significantly reduced temperature in cerebral cortex from 37.2 +/- 0.1 to 33.4 +/- 0.4 degrees C and in striatum from 37.5 +/- 0.2 to 33.9 +/- 0.4 degrees C. The significant hypothermia remained for up to 60 minutes after reperfusion. Significant (P < 0.01) reductions in infarct volume (approximately 90%) were evident after 48 hours of reperfusion. In ischemic rats that received the same amount of cold saline systemically through a femoral artery, a mild hypothermia was induced only in the cerebral cortex (35.3 +/- 0.2 degrees C) and returned to normal within 5 minutes. No significant reductions in infarct volume were observed in this group or in the ischemic group with local warm saline infusion or without infusion. Furthermore, brain-cooling infusion significantly (P < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion. This improvement continued for up to 28 days after reperfusion.
Local prereperfusion infusion effectively induced hypothermia and ameliorated brain injury from stroke. Clinically, this procedure could be used in acute stroke treatment, possibly in combination with intra-arterial thrombolysis or mechanical disruption of clot by means of a microcatheter.
低温的神经保护作用早已得到认可。目前通过全身表面降温诱导的低温用于中风治疗，主要由于管理问题和严重副作用（如肺炎）而受到限制。本研究的目的是确定向缺血区域局部输注生理盐水是否能诱导局部脑冷却和神经保护。
采用一种新方法，用中空丝线阻断大鼠大脑中动脉3小时，并在再灌注前向大脑中动脉供血区域局部输注6毫升冷生理盐水（20℃）10分钟。
冷生理盐水输注迅速且显著地将大脑皮层温度从37.2±0.1℃降至33.4±0.4℃，纹状体温度从37.5±0.2℃降至33.9±0.4℃。再灌注后显著低温持续长达60分钟。再灌注48小时后，梗死体积显著（P<0.01）减小（约90%）。在通过股动脉全身接受相同量冷生理盐水的缺血大鼠中，仅大脑皮层诱导出轻度低温（35.3±0.2℃），并在5分钟内恢复正常。在该组或局部输注温生理盐水或未输注的缺血组中，未观察到梗死体积有显著减小。此外，脑冷却输注在再灌注14天后显著（P<0.01）改善了缺血大鼠的运动行为。这种改善在再灌注后持续长达28天。
再灌注前局部输注有效地诱导了低温并减轻了中风引起的脑损伤。临床上，该方法可用于急性中风治疗，可能与动脉内溶栓或通过微导管机械性血栓溶解联合使用。
