Koistinaho J, Pasonen S, Yrjänheikki J, Chan P H
A.I. Virtanen Institute, University of Kuopio, Finland.
Stroke. 1999 Jan;30(1):114-9. doi: 10.1161/01.str.30.1.114.
Plasma glucose and spreading depression (SD) are both determinants of brain ischemia. The purpose of this study was to examine whether plasma glucose affects SD-induced gene expression in the cortex.
SD was induced by topical application of KCl. Hyperglycemia and hypoglycemia were induced by intraperitoneal injection of glucose and insulin, respectively. The expression of c-fos, cyclooxygenase-2 (COX-2), protein kinase C-delta (PKCdelta), and heme oxygenase-1 (HO-1) was determined by in situ hybridization.
SD alone induced expression of c-fos (by 340%), COX-2 (210%), HO-1 (470%), and PKCdelta (410%). Hypoglycemia (2.4+/-0.9 mmol/L) alone did not induce gene expression, and hyperglycemia (22.1+/-3.7 mmol/L) alone induced only c-fos by 42%. When hypoglycemia was induced 30 minutes before SD, c-fos induction was enhanced by 145%, but the induction of HO-1 and PKCdelta was reduced to 43% and 64%, respectively. When hyperglycemia was induced 30 minutes before SD, c-fos induction was enhanced by 388% and COX-2 expression by 53%, whereas the induction of PKCdelta and HO-1 was reduced to 54% and 51%, respectively. The frequency, amplitude, and duration of direct current potentials were unaltered in hyperglycemic SD animals, whereas in hypoglycemic animals the duration was increased by 47%.
While SD induces expression of several genes, the availability of glucose regulates the extent of the gene induction. The effect of glucose is different on early-response genes (c-fos and COX-2) compared with late-response genes. Plasma glucose may contribute to neuronal damage partially by regulating gene expression.
血糖和扩散性抑制（SD）都是脑缺血的决定因素。本研究的目的是探讨血糖是否会影响SD诱导的皮质基因表达。
通过局部应用氯化钾诱导SD。分别通过腹腔注射葡萄糖和胰岛素诱导高血糖和低血糖。采用原位杂交法检测c-fos、环氧化酶-2（COX-2）、蛋白激酶C-δ（PKCδ）和血红素加氧酶-1（HO-1）的表达。
单独SD诱导c-fos表达增加340%、COX-2增加210%、HO-1增加470%、PKCδ增加410%。单独低血糖（2.4±0.9 mmol/L）未诱导基因表达，单独高血糖（22.1±3.7 mmol/L）仅诱导c-fos增加42%。在SD前30分钟诱导低血糖时，c-fos的诱导增加145%，但HO-1和PKCδ的诱导分别降至43%和64%。在SD前30分钟诱导高血糖时，c-fos的诱导增加388%，COX-2表达增加53%，而PKCδ和HO-1的诱导分别降至54%和51%。高血糖SD动物的直流电位频率、幅度和持续时间未改变，而低血糖动物的持续时间增加47%。
虽然SD诱导多种基因表达，但葡萄糖的可用性调节基因诱导的程度。与晚期反应基因相比，葡萄糖对早期反应基因（c-fos和COX-2）的影响不同。血糖可能部分通过调节基因表达导致神经元损伤。
