Theodorsson Annette, Holm Lovisa, Theodorsson Elvar
Department of Biomedicine and Surgery, IBK/Clinical Chemistry, Division of Clinical Chemistry, University Hospital, SE-581 85 Linkoping, Sweden.
Neuropeptides. 2008 Feb;42(1):79-87. doi: 10.1016/j.npep.2007.09.008. Epub 2007 Nov 28.
The effects of hypothermia on galanin concentrations and the relation between ischemic brain lesions, hypothermia and galanin concentrations in a transient and focal rat stroke model were investigated in order to elucidate whether hypothermia-induced alterations in galanin concentrations could constitute a part of the established neuroprotective effect of hypothermia. Female rats were allocated to normothermia (37 degrees C) or hypothermia (33 degrees C) treatments during a 60 min microclip middle cerebral artery occlusion. The ischemic lesions were visualized after observation periods of 2 or 7 days and the concentration of galanin measured by radioimmunoassay in extracts of punch biopsies from both the lesioned and the contralateral control hemisphere. Hypothermia-induced an overall increase in the concentrations of immunoreactive galanin (p<0.001). The elevated galanin levels were predominantly found in the non-ischemic control hemisphere, in the hippocampus, thalamus and the posterior part of parietal cortex. The galanin concentrations were lower in the ischemic hemisphere in both the normo- and hypothermic animals compared to the corresponding contra lateral intact hemisphere (p=0.049). The factor of time, 2 respectively 7 days, did not show any significant difference regarding the galanin concentrations (p=0.844). Multivariate analyses of variance revealed significant effect of ischemia on the size of the ischemic brain lesions (p=0.001) but no overall effect of temperature when data from both 2 and 7 days observation periods were analyzed together. The ischemic lesions were generally larger at 33 degrees after 2 days (p=0.230). Prolonged observation time of 7 days resulted in a significant reduction of the ischemic brain lesion (p=0.011) with smaller ischemic lesions in the hypothermic group. Our data support the notion that hypothermia-induced increase in the tissue concentrations of galanin in the brain are the result of changes from optimal homeostatic conditions - the hypothermia-induced stress - rather than the ischemia/re-perfusion lesion induced changes in galanin concentrations. Hypothermia-induced elevation in galanin concentration is therefore not likely to be amongst the major protective mechanisms of hypothermia.
为了阐明低温诱导的甘丙肽浓度变化是否构成低温既定神经保护作用的一部分,研究了低温对甘丙肽浓度的影响以及在短暂性局灶性大鼠中风模型中缺血性脑损伤、低温与甘丙肽浓度之间的关系。在60分钟的大脑中动脉微夹闭期间,将雌性大鼠分为正常体温(37摄氏度)或低温(33摄氏度)处理组。在2天或7天的观察期后观察缺血性损伤,并通过放射免疫分析法测量损伤半球和对侧对照半球的穿孔活检提取物中甘丙肽的浓度。低温导致免疫反应性甘丙肽浓度总体升高(p<0.001)。升高的甘丙肽水平主要见于非缺血性对照半球、海马体、丘脑和顶叶皮质后部。与相应的对侧完整半球相比,正常体温和低温动物的缺血半球中甘丙肽浓度均较低(p=0.049)。时间因素,分别为2天和7天,在甘丙肽浓度方面未显示任何显著差异(p=0.844)。多因素方差分析显示,缺血对缺血性脑损伤的大小有显著影响(p=0.001),但当一起分析2天和7天观察期的数据时,温度没有总体影响。2天后,33摄氏度时的缺血性损伤通常更大(p=0.230)。延长至7天的观察时间导致缺血性脑损伤显著减少(p=0.011),低温组的缺血性损伤较小。我们的数据支持这样一种观点,即低温诱导的大脑中甘丙肽组织浓度增加是最佳稳态条件变化——低温诱导的应激——的结果,而不是缺血/再灌注损伤诱导的甘丙肽浓度变化。因此,低温诱导的甘丙肽浓度升高不太可能是低温的主要保护机制之一。