We have previously shown that hypoxia induces both acute and chronic epileptogenic effects that are age dependent. Global hypoxia (3-4% O2) induces seizure activity in the developing brain [postnatal day (P)10-12] but not at younger or older ages. Adult rats with prior seizures induced by hypoxia at P10 show increased seizure susceptibility to chemical convulsants compared with controls. In the present study, we tested the hypothesis that acute and chronic epileptogenic effects of hypoxia are demonstrable in hippocampus both in vivo and in vitro. Depth electrode recordings confirmed the presence of ictal activity within hippocampus in P10 rats during global hypoxia. Hippocampal slices prepared from P10 pups killed at 10 min after recovery from hypoxia showed evidence of increased excitability. Extracellular field recordings revealed that the amplitude and duration of long-term potentiation (LTP) was increased significantly in area CA1 of hippocampal slices removed from hypoxic pups. In addition, extracellular recordings within areas CA1 and CA3 showed significantly longer afterdischarge durations in response to kindling stimuli in slices from hypoxic pups compared with controls. To evaluate whether there were also long-term changes in hippocampal excitability, hippocampal slices were prepared from adult rats that had underwent hypoxia at P10 and compared with slices from adult litter-mate controls. A Mg2+-free medium was superfused to induce epileptiform activity within the slices. Extracellular recordings from stratum pyramidale of area CA1 showed that Mg2+-free media induced significantly more frequent ictal discharges in slices from previously hypoxic rats compared with controls. These results provide evidence that the naturally occurring stimulus of hypoxia can result in both acute and chronic changes in the excitability of the CA1 neuronal network. These results parallel our previous in vivo studies demonstrating that global hypoxia acutely increases excitability in the immature brain and that hypoxia during the age window approximately P10 results in long-lasting increases in seizure susceptibility within hippocampus. Our results suggest that the age-dependent epileptogenic effects of hypoxia are in part mediated by a direct and permanent effect on neuronal excitability within hippocampal neuronal networks.

Aims/hypothesis The endogenous production of stromal cell-derived factor-1 (SDF-1) in beta cells in transgenic mice attenuates the development of diabetes in response to streptozotocin. Here we propose that beta cell injury induces SDF-1 production, and the SDF-1/chemokine (C-X-C motif) receptor 4 (CXCR4) interaction auto-activates Sdf1 expression, resulting in the autocrine production of SDF-1 by beta cells and the paracrine activation of glucagon-like peptide-1 (GLP-1) production by alpha cells. Methods SDF-1 production in adult mouse and human islets and rat INS-1 cells was measured in models of beta cell injury. The paracrine actions of SDF-1 on GLP-1 production in alpha cells were explored. The potential synergism between the growth-promoting actions of GLP-1 and the pro-survival actions of SDF-1 on the preservation of cell mass was evaluated by cell viability assays. Results In adult islets and INS-1 cells, Sdf1 expression was re-induced in response to injury. The interaction of SDF-1 with its receptor on alphaTC1 cells activated protein kinase Akt, stimulated cell proliferation and induced the expression of prohormone convertase 1/3 and the consequent production of GLP-1 in alpha cells. The combination of GLP-1 and SDF-1 additively enhanced both the growth and longevity of INS-1 beta cells. Conclusions/interpretation The results of these studies suggest that in response to beta cell injury and the ensuing induction of SDF-1, the biological function of alpha cells switches from the production of glucagon to the provision of the local growth factor GLP-1 which, in combination with SDF-1, promotes the growth, survival and viability of the beta cells.

Abstract. Substantial anthropogenic emissions from China have resulted in serious air pollution, and this has generated considerable academic and public concern. The physical transport of air pollutants in the atmosphere has been extensively investigated; however, understanding the mechanisms how the pollutant was transferred through economic and trade activities remains a challenge. For the first time, we quantified and tracked China's air pollutant emission flows embodied in interprovincial trade, using a multiregional input-output model framework. Trade relative emissions for four key air pollutants (primary fine particle matter, sulfur dioxide, nitrogen oxides and non-methane volatile organic compounds) were assessed for 2007 in each Chinese province. We found that emissions were significantly redistributed among provinces owing to interprovincial trade. Large amounts of emissions were embodied in the imports of eastern regions from northern and central regions, and these were determined by differences in regional economic status and environmental policy. It is suggested that measures should be introduced to reduce air pollution by integrating cross-regional consumers and producers within national agreements to encourage efficiency improvement in the supply chain and optimize consumption structure internationally. The consumption-based air pollutant emission inventory developed in this work can be further used to attribute pollution to various economic activities and final demand types with the aid of air quality models.