An astrocytic protein S-100beta enhances the expression of inducible nitric oxide synthase in cultured astrocytes at micromolar concentrations, leading to nitric oxide-mediated death of cocultured neurons. The present study examined whether S-100beta production by reactive astrocytes accumulating within the periinfarct area was related to delayed expansion of infarct volume after permanent middle cerebral artery occlusion in the rat. After rapid increases during the initial 24 hours, the increase of infarct volume then decelerated while maintaining the increasing tendency until 168 hours in this model, attaining a significant difference compared with that at 24 hours. In the periinfarct area, the number of reactive astrocytes expressing both S-100 and glial fibrillary acidic protein, the tissue level of S-100beta as measured by the sandwich enzyme-linked immunosolvent assay method using anti-S-100beta monoclonal antibody, and the number of terminal deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;-triphosphate-biotin nick end labeling-positive cells were significantly increased preceding the delayed expansion of infarct volume. The CSF concentration of S-100beta showed a biphasic increase, presumably reflecting the immediate release from astrocytes within the ischemic core and the subsequent production in reactive astrocytes within the periinfarct area. These results show for the first time that the enhanced synthesis of S-100beta by reactive astrocytes participates in the inflammatory responses within the periinfarct area, which may be related to the occurrence of delayed infarct expansion as a major component of the cytokine network.

A novel agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), has a unique property in that it modulates functions of activated cultured astrocytes, including pronounced inhibition of S-100beta synthesis. The present study examined whether administration of this agent would mitigate the delayed expansion of infarct volume and the neurologic deficits after permanent middle cerebral artery occlusion (pMCAO) in rats. Daily intravenous administration of ONO-2506 (10 mg/kg) abolished the delayed infarct expansion between 24 and 168 hours after pMCAO, whereas the acute infarct expansion until 24 hours was unaffected. The agent significantly reduced the expression of S-100beta and glial fibrillary acidic protein in the activated astrocytes and the number of terminal deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;-triphosphate-biotin nick end labeling-positive cells in the periinfarct area. The neurologic deficits were significantly improved, compared with the vehicle-treated groups, as early as 24 hours after the initial administration of ONO-2506. The agent had a wide therapeutic time window of 0 to 48 hours after pMCAO. These results indicate that because of the pharmacologic modulation of astrocytic activation induced by ONO-2506, symptoms can regress whereas delayed expansion of the lesion is arrested. Pharmacologic modulation of astrocytic activation may confer a novel therapeutic strategy against stroke.

Invasion of alien species has been shown to cause detrimental effects on habitats of native species. Insect pollinators represent such examples; the introduction of commercial bumble bee species for crop pollination has resulted in competition for an ecological niche with native species, genetic disturbance caused by mating with native species, and pathogen spillover to native species. The European honey bee, Apis mellifera, was first introduced into Japan for apiculture in 1877, and queen bees have been imported from several countries for many years. However, its effects on Japanese native honey bee, Apis cerana japonica, have never been addressed. We thus conducted the survey of honey bee viruses and Acarapis mites using both A. mellifera and A. c. japonica colonies to examine their infestation in native and non-native honey bee species in Japan. Honey bee viruses, Deformed wing virus (DWV), Black queen cell virus (BQCV), Israeli acute paralysis virus (IAPV), and Sacbrood virus (SBV), were found in both A. mellifera and A. c. japonica colonies; however, the infection frequency of viruses in A. c. japonica was lower than that in A. mellifera colonies. Based on the phylogenies of DWV, BQCV, and SBV isolates from A. mellifera and A. c. japonica, DWV and BQCV may infect both honey bee species; meanwhile, SBV has a clear species barrier. For the first time in Japan, tracheal mite (Acarapis woodi) was specifically found in the dead honey bees from collapsing A. c. japonica colonies. This paper thus provides further evidence that tracheal-mite-infested honey bee colonies can die during cool winters with no other disease present. These results demonstrate the infestation of native honey bees by parasite and pathogens of non-native honey bees that are traded globally.