Search

Growth inhibitory factor (GIF) is a small protein belonging to the metallothionein family that has the capacity to inhibit neuronal survival and neurite formation in vitro. This study was conducted to investigate the role of GIF in the brain afflicted with ischemic injury. We used the in situ hybridization technique and Northern blot analysis to study the changes in GIF messenger RNA (mRNA) expression in a rat focal ischemia model. On the first day, the expression tended to decrease in the hemisphere ipsilateral to the injury. It returned to normal levels on the second day except for the central area of the middle cerebral artery (MCA) territory. On the third and fourth day, the expression increased diffusely in the hemisphere of the affected side, including the subcortical area. Two weeks after ischemia, the GIF mRNA expression increased again but only in the peri-infarcted area. Down-regulation of GIF on the first day in the cortex ipsilateral to the infarction might promote neurite sprouting. The subsequent increase in GIF mRNA expression on the third and fourth day might be a symptom of neurons attempting to inhibit excessive neurite outgrowth, or to protect themselves against toxicity caused by oxygen radicals. The later increase in the limited area around the infarction may be related to astroglial reaction. Growth inhibitory factor may play an important role in regulating the central nervous system after ischemic insults.

Myo-inositol is one of the major organic osmolytes in the brain. It is accumulated into cells through an Na+/ myo-inositol cotransporter (SMIT) that is regulated by extracellular tonicity. To investigate the role of SMIT in the brain after cerebral ischemia, we examined expression of SMIT mRNA in the rat brain after middle cerebral artery occlusion, which would reflect alteration of extracellular tonicity. The expression of SMIT mRNA was markedly increased 12 h after surgery in the cortex of the affected side and lasted until the second day. Increased expression was also found in the contralateral cingulate cortex. Up-regulated expression was found predominantly in the neurons in remote areas, although nonneuronal cells adjacent to the ischemic core also expressed this mRNA. These results suggest that cerebral ischemia causes extensive osmotic stress in brain and that the neuronal cells respond to this stress by increasing SMIT expression.

We investigated the effects of prostaglandin (PG) E1 on the hypoxic injury of fetal rat hippocampal cells. Primary hippocampal cell cultures (embryonic day 18) were established and maintained. After 72 h in culture, PGE1 was added to the serum-free medium at a final concentration of 10(-5)-10(-9) M. Cultures were divided into two groups: The normoxia group was in culture for another 48 h, and the hypoxia group was exposed to 24 h of hypoxia followed by continuation of culture for another 24 h. As a quantitative measure of cell death, lactate dehydrogenase (LDH) activity was estimated in the culture medium. The LDH activity, released by the hypoxic insult, was significantly smaller with PGE1 treatment at 10(-6), 10(-7), and 10(-8) M (p < 0.01) and 10(-9) M (p < 0.05) compared with the control. No differences in the LDH activities were observed in the normoxia group. Glial culture was not affected by the hypoxia. Western blot analysis showed an increased induction of 62-kDa c-Fos and 58, 60, and 66 kDa Myc proteins in rat hippocampal cells with 10(-7) M PGE1 treatment. We conclude that PGE1 at concentrations of 10(-6)-10(-9) M protects rat hippocampal neurons against hypoxic insult.