No abstract

Postischemic seizures are associated with worsened outcome following stroke, but the underlying pathophysiology is poorly understood. Here we examined acute seizures in adult mice following hypoxia-ischemia (HI) via combined behavioral, electrophysiological, and histological assessments. C57BL/6 mice aged 4-9 months received a permanent occlusion of the right common carotid artery and then underwent a systemic hypoxic episode. Generalized motor seizures were observed within 72 h following HI. These seizures occurred nearly exclusively in animals with extensive brain injury in the hemisphere ipsilateral to the carotid occlusion, but their generation was not associated with electroencephalographic discharges in bilateral hippocampal and neocortical recordings. Animals exhibiting these seizures had a high rate of mortality, and post-HI treatments with diazepam and phenytoin greatly suppressed these behavioral seizures and improved post-HI animal survival. Based on these data, we conclude that these seizures are a consequence of HI brain injury, contribute to worsened outcome following HI, and that they originate from deep subcortical structures.

Although neural c-Jun is essential for successful peripheral nerve regeneration, the cellular basis of this effect and the impact of c-Jun activation are incompletely understood. In the current study, we explored the effects of neuron-selective c-Jun deletion, substitution of serine 63 and 73 phosphoacceptor sites with non-phosphorylatable alanine, and deletion of Jun N-terminal kinases 1, 2 and 3 in mouse facial nerve regeneration. Removal of the floxed c-jun gene in facial motoneurons using cre recombinase under control of a neuron-specific synapsin promoter (junΔS) abolished basal and injury-induced neuronal c-Jun immunoreactivity, as well as most of the molecular responses following facial axotomy. Absence of neuronal Jun reduced the speed of axonal regeneration following crush, and prevented most cut axons from reconnecting to their target, significantly reducing functional recovery. Despite blocking cell death, this was associated with a large number of shrunken neurons. Finally, junΔS mutants also had diminished astrocyte and microglial activation and T-cell influx, suggesting that these non-neuronal responses depend on the release of Jun-dependent signals from neighboring injured motoneurons. The effects of substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global deletion of individual kinases responsible for N-terminal c-Jun phosphorylation were mild. junAA mutants showed decrease in neuronal cell size, a moderate reduction in post-axotomy CD44 levels and slightly increased astrogliosis. Deletion of Jun N-terminal kinase (JNK)1 or JNK3 showed delayed functional recovery; deletion of JNK3 also interfered with T-cell influx, and reduced CD44 levels. Deletion of JNK2 had no effect. Thus, neuronal c-Jun is needed in regeneration, but JNK phosphorylation of the N-terminus mostly appears to not be required for its function.

The last decade has seen significant growth in scientific understanding and public awareness of autism. There is still a long road ahead before this awareness can be matched with parallel improvements in evidence-based practice. The process of translating evidence into community care has been hampered by the seeming disconnect between the mainstream scientific research agenda and the immediate priorities of many communities. The need for community engagement in the process of translating knowledge into impact has been recognized. However, there remains little consensus or empirical data regarding the process of such engagement and how to measure its impact. We shed light on a number of engagement models and tools, previously advocated in health research, as they apply to autism research. Furthermore, we illustrate the utility of such tools in supporting identification of knowledge gaps and priorities, using two community-based case studies. The case studies illustrate that information generated from research is indeed relevant and critical for knowledge users in the community. Simple and systematic methods can support the translation and uptake of knowledge in diverse communities, therefore enhancing engagement with research and bridging research findings with immediate community needs.