Yamashita K, Vogel P, Fritze K, Back T, Hossmann K A, Wiessner C
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
Brain Res. 1996 Oct 7;735(2):285-97. doi: 10.1016/0006-8993(96)00578-1.
We investigated the temporo-spatial expression of astrocyte glial fibrillary acidic protein (gfap) and sulfated glycoprotein 2 (sgp-2) mRNAs in comparison to 70-kDa heat shock protein (hsp70) mRNA by in situ hybridisation in rats subjected to permanent occlusion of the middle cerebral artery (MCA). Gfap mRNA started to increase in the cingulate cortex of the lesioned hemisphere 6 h after MCA occlusion and gradually spread over the lateral part of the ipsilateral cortex and the striatum from 12 h to 3 days, peaking at 3 days after MCA occlusion. Gfap mRNA also increased in the contralateral cingulate cortex and corpus callosum at 12 and 24 h. Hsp70 mRNA increased markedly in the ipsilateral cortex adjacent to the ischemic lesion, and slightly within the lesion area from 3 to 24 h and disappeared after 3 days. By 7 days, gfap and sgp-2 mRNAs were increased markedly in the peri-infarct area, and in the ipsilateral thalamus parallel with the delayed neuronal damage, whereas the widespread increase of gfap mRNA in the ipsilateral hemisphere declined. Post-occlusion treatment with the glutamate receptor antagonists MK-801 and NBQX slightly attenuate the induction of gfap but did not qualitatively affect the topical expression pattern. Within the cingulate cortex MK-801 treatment resulted in a significant decrease of the signal intensity at all survival times, reflecting most likely an attenuation of lesion-induced spreading depression like depolarization waves by MK-801. The area of hsp70 expression was reduced by both MK-801 and NBQX, most likely reflecting the decrease of the lesion area by both treatment regimens. Our study thus revealed an early and widespread increase of gfap mRNA in the non-ischemic area including the contralateral hemisphere starting between 3 and 6 h, and a delayed circumscribed expression in the peri-infarct border zone after 1 week. Comparison with the expression of hsp70 mRNA suggests that the absence of an early gfap mRNA induction in the peri-lesion zone reflects an impairment of astrocytic function which may be of importance for infarct growth during the early evolution of the pathological process.
我们通过原位杂交技术，在大脑中动脉（MCA）永久性闭塞的大鼠中，研究了星形胶质细胞胶质纤维酸性蛋白（gfap）和硫酸化糖蛋白2（sgp - 2）mRNA与70 kDa热休克蛋白（hsp70）mRNA的时空表达情况。MCA闭塞6小时后，gfap mRNA开始在损伤半球的扣带回皮质中增加，并在12小时至3天内逐渐扩散到同侧皮质的外侧部分和纹状体，在MCA闭塞后3天达到峰值。在12小时和24小时时，对侧扣带回皮质和胼胝体中的gfap mRNA也增加。Hsp70 mRNA在缺血性病变相邻的同侧皮质中显著增加，在病变区域内从3小时至24小时略有增加，并在3天后消失。到7天时，gfap和sgp - 2 mRNA在梗死周边区域以及同侧丘脑中显著增加，与延迟性神经元损伤平行，而同侧半球中gfap mRNA的广泛增加则下降。用谷氨酸受体拮抗剂MK - 801和NBQX进行闭塞后治疗，略微减弱了gfap的诱导，但未定性地影响局部表达模式。在扣带回皮质内，MK - 801治疗在所有存活时间均导致信号强度显著降低，这很可能反映了MK - 801对损伤诱导的扩散性抑制样去极化波的减弱作用。MK - 801和NBQX均使hsp70表达区域减小，这很可能反映了两种治疗方案均使病变区域减小。我们的研究因此揭示，在包括对侧半球在内的非缺血区域，gfap mRNA在3至6小时开始出现早期广泛增加，而在1周后梗死周边边界区域出现延迟的局限性表达。与hsp70 mRNA表达的比较表明，病变周边区域缺乏早期gfap mRNA诱导反映了星形胶质细胞功能受损，这可能在病理过程的早期演变中对梗死灶扩大具有重要意义。
