Kim Y, Truettner J, Zhao W, Busto R, Ginsberg M D
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, FL, USA.
J Neurol Sci. 1998 Jul 15;159(1):1-10. doi: 10.1016/s0022-510x(98)00146-4.
We have recently shown that moderate hyperthermia, even if delayed, markedly enlarges the volume of an acute ischemic infarct. In the current study, we used in situ hybridization autoradiography to assess the effects of delayed hyperthermia on the regional expression of messenger RNA (mRNA) for the immediate early genes c-fos and c-jun, the inducible heat-shock protein 70 (hsp70) and glial fibrillary acid protein (GFAP) following 1 h of transient middle cerebral artery occlusion (MCAo) produced in rats by the insertion of an intraluminal suture. Sham-occluded rats were also studied. One day after MCAo, rats were placed into a heating chamber, where cranial temperature was either maintained at 37-38 degrees C (normothermic group) or was elevated to 40 degrees C (hyperthermic group) for 3 h. At either 2 or 24 h thereafter, brains were studied by in situ hybridization. Low-level constitutive c-fos and c-jun expression in sham-occluded rats was unaffected by delayed temperature manipulation. Prior MCAo decreased c-fos and c-jun mRNA in the affected striatum and overlying cortex. In rats studied 2 h after delayed hyperthermia, however, c-fos mRNA was markedly increased in ipsilateral cingulate cortex. By contrast, the pattern of c-jun mRNA was similar in rats with prior MCAo irrespective of delayed normothermia or hyperthermia: increased expression involved ipsilateral cingulate and paramedian cortical areas. Bilateral increases in hsp70 expression were produced by hyperthermia alone, and hsp70 mRNA was densely increased throughout the ischemic cortex and striatum following MCAo, while delayed hyperthermia altered this pattern by extending the zone of increased hsp70 message to cingulate and paramedian cortical areas at 2 h. GFAP mRNA was decreased within the previously ischemic field but increased in surrounding regions. The induction of c-fos and hsp70 message in tissue regions abutting zones of enhanced injury in brains with delayed postischemic hyperthermia indicates that these zones have been additionally stressed: these gene responses may possibly contribute to the protection of these threatened regions.
我们最近发现，适度的体温过高，即使有所延迟，也会显著增大急性缺血性梗死灶的体积。在本研究中，我们采用原位杂交放射自显影术，评估延迟性体温过高对即刻早期基因c-fos和c-jun、诱导性热休克蛋白70（hsp70）以及胶质纤维酸性蛋白（GFAP）信使核糖核酸（mRNA）区域表达的影响。这些基因是在大鼠因插入管腔内缝合线导致大脑中动脉短暂闭塞（MCAo）一小时后出现的。同时也对假闭塞大鼠进行了研究。MCAo一天后，将大鼠放入加热室，颅温要么维持在37 - 38摄氏度（正常体温组），要么升高到40摄氏度（体温过高组），持续3小时。此后2小时或24小时，通过原位杂交对大脑进行研究。假闭塞大鼠中低水平的组成型c-fos和c-jun表达不受延迟性温度调控的影响。先前的MCAo降低了受影响纹状体和覆盖皮质中的c-fos和c-jun mRNA。然而，在延迟性体温过高后2小时进行研究的大鼠中，同侧扣带回皮质中的c-fos mRNA显著增加。相比之下，先前有MCAo的大鼠中，无论延迟性正常体温还是体温过高，c-jun mRNA的模式相似：表达增加涉及同侧扣带回和旁正中皮质区域。单独的体温过高导致hsp70表达双侧增加，MCAo后hsp70 mRNA在整个缺血皮质和纹状体中密集增加，而延迟性体温过高通过在2小时时将hsp70信息增加区域扩展到扣带回和旁正中皮质区域改变了这种模式。GFAP mRNA在先前缺血区域内减少，但在周围区域增加。在缺血后延迟性体温过高的大脑中，与损伤增强区域相邻的组织区域中c-fos和hsp70信息的诱导表明这些区域受到了额外的应激：这些基因反应可能有助于保护这些受到威胁的区域。
