During focal ischemia, neurons in a densely ischemic focus are usually doomed unless reperfusion is quickly instituted. In contrast, neurons in a less densely ischemic penumbral zone remain viable for at least 4-8 h and then die (Siesjo, 1992). Recent studies have provided evi dence that some neuronal subpopulations may die after permanent or transient cerebral ischemia via apoptosis or programmed cell death following the activation of an endogenous cell death program (Linnik et aI., 1993; Li et aI., 1995).The best characterized genetic system of programmed cell death (peD) is the worm Caenorhabditis elegans (c.

Nitric oxide from neuronal cells plays detrimental roles in glutamate neurotoxicity and in focal brain ischemia. Nitric oxide directly damages DNA, and breaks in the DNA strands activate poly(ADP-ribose) polymerase (PARP), which brings poly(ADP-ribosyl)ation of the nuclear proteins. The excessive activation of PARP is thought to cause depletion of ATP and the energy failure resulting in cell death. To clarify the involvement of poly(ADP-ribosyl)ation in ischemic insult, we examined poly(ADP ribosyl)ation by immunohistochemical methods and the protective effect of 3-aminobenzamide, which is a PARP inhibitor, on focal brain ischemia using an intraluminal permanent middle cerebral artery occlusion model in rats. Poly(ADP ribosyl)ation was widely and markedly detected 2 hours after the ischemic insult in the cerebral cortex and striatum in which infarction developed 24 hours later. The enhanced immunoreactivity of poly(ADP-ribose) gradually decreased, and 16 hours later, no immunoreactivity was detected. Intraventricular administration of 3-aminobenzamide (1 to 30 mg/kg) 30 minutes before the ischemic insult decreased infarction volume in a dose-dependent manner along with the immunohistochemical reduction of poly(ADP-ribosyl)ation. Pretreatment with 7-nitroindazole (25 mg/kg, intraperitoneally), a selective neuronal nitric oxide synthetase inhibitor, partially reduced poly(ADP-ribosyl)ation. These data suggest the involvement of poly(ADP-ribosyl)ation in the development of cerebral infarction.

Thioredoxin (TRX) is a small, multifunctional protein with a redox-active site and multiple biological functions that include reducing activity for reactive oxygen intermediates. We assayed TRX and TRX mRNA by immunohistochemical methods and hybridization experiments in the rat brain after middle cerebral artery (MCA) occlusion. During ischemia, the immunoreactivity for TRX decreased; it disappeared after MCA occlusion in the ischemic regions. It rapidly decreased and nearly disappeared at 4 and 16 hours after MCA occlusion in the lateral striatum and frontoparietal cortex, respectively. On the other hand, in the perifocal ischemic region, the penumbra, TRX immunoreactivity began to increase 4 hours after MCA occlusion and continued to increase until 24 hours after occlusion. In hybridization experiments, TRX mRNA decreased and nearly disappeared 4 hours after MCA occlusion in the lateral striatum. In the frontoparietal cortex, it decreased until 24 hours after MCA occlusion. In the perifocal ischemic region, TRX mRNA began to increase 4 hours after MCA occlusion and continued to increase until 24 hours. Northern blot analysis showed that total TRX mRNA in the operated hemispheres was induced from 8 hours and increased until 24 hours after the surgical procedures. We previously reported that recombinant TRX promotes the in vitro survival of primary cultured neurons. We now suggest that TRX in the penumbra has neuroprotective functions and that decreased levels of TRX in the ischemic core modify neuronal damage during focal brain ischemia.

Delayed neuronal death (DND) in CA1 region after transient global ischemia is a well-known phenomenon, but its mechanism has not been clarified. In order to examine the involvement of nitric oxide (NO) in DND, 7-nitro indazole (7NI), a selective neuronal NO synthase (nNOS) inhibitor, and FK506, an immunosuppressant which also inhibits nNOS, were administered intraperitoneally during and after transient global ischemia in gerbil. FK506 moderately ameliorated DND in a dose-dependent manner. However, 7NI showed only minor neuroprotective effects. These results show that DND is not mainly mediated by NO production via nNOS, and FK506 acts as a neuroprotective agent via unknown pathways other than nNOS inhibition.

Background:Multinodular and vacuolated neuronal tumor (MVNT) is a benign neuronal tumor that is newly recognized as architectural appearance that may be related to ganglion cell tumors in 2016 World Health Organization Classification of Tumors of the Central Nervous System. Herein, we report a case of MVNT in a 60-year-old man with a thorough literature review.Case Description:A 60-year-old male was pointed out the presence of intracerebral neoplasm located in left frontal lobe by a comprehensive medical examination. We suspected dysembryoplastic neuroepithelial tumors and proposed him to wait and see, but he wished to undergo surgery for diagnosis. We performed en bloc resection and pathological findings were consistent with MVNT. He was discharged on the 8th day after the operation without any complications. He remained stable without recurrence at the 16-month postoperative follow-up.Conclusions:Further studies may be helpful to fully understand the radiological and histological findings of MVNT development. As a result, we will be able to prevent the aggressive treatment if we established their major features.