The 70-kDa heat shock protein (Hsp70) is involved in protecting the brain from a variety of insults including stroke. Although the mechanism has been largely considered to be because of its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory responses. To explore how and whether Hsp70 regulate immune responses in brain ischemia, mice overexpressing Hsp70 (Hsp Tg) were subjected to 2 h middle cerebral artery occlusion, followed by 24 h reperfusion. Parallel experiments were performed using a brain inflammation model. Hsp Tg microglia cocultured with astrocytes were used to evaluate the direct effects of Hsp70 on cytotoxicity of microglia. Compared with wild-type (Wt) littermates, Hsp Tg mice showed decreased infarct size and improved neurological deficits. The number of activated microglia/macrophages were also reduced in ischemic brains of Hsp Tg mice. Similar observations were made in a model of brain inflammation that does not result in brain cell death. Overexpression of Hsp70 in microglia completely prevented microglia-induced cytotoxicity to astrocytes. Activation of the inflammatory transcription factor, nuclear factor-kappaB (NF-kappaB) was inhibited significantly in Hsp Tg mice and microglia. This was associated with decreased phosphorylation of NF-kappaB inhibitor protein, IkappaBalpha, and decreased expression of several NFkappaB-regulated genes. Co-immunoprecipitation studies revealed an interaction of Hsp70 with NF-kappaB and IkappaBalpha, but not with IkappaB kinase, IKKgamma, suggesting that Hsp70 binds to the NF-kappaB:IkappaB complex preventing IkappaB phosphorylation by IKK. The findings of the present work establish an anti-inflammatory role for Hsp70 in the context of brain ischemia as a novel mechanism of protection.

Ischemic stroke is characterized by the disruption of cerebral blood flow (CBF). This reduction of CBF results in energy failure and secondary biochemical disturbances, eliciting a robust in situ inflammatory response. Post-ischemic inflammation is a dynamic process involving a complicated set of interactions among various inflammatory cells and molecules. The resident inflammatory brain cells, microglia, are especially activated in response to ischemic insults, many of which are regulated by nuclear transcription factor, kappa B (NF-kappaB). As a result, several inflammatory genes are expressed, leading to local generation of various cytokines, which in turn promulgate inflammatory signals. Meanwhile, endothelial cells lining the local cerebral blood vessels are stimulated to produce adhesion molecules, causing the migration of peripheral circulating leukocytes into the compromised brain tissue, an event that amplifies inflammatory signaling cascades. Post-ischemic inflammation appears to serve multiple purposes, depending on its timing and magnitude, as well as the topographic distribution of various inflammatory molecules. Data from experimental manipulations of some inflammatory molecules are yielding insight into therapeutic strategies for ischemic stroke. This review focuses on some recent advances regarding the regulation of inflammatory signaling pathways, the detrimental effects of post-ischemic inflammation and the potential molecular targets for ischemic stroke therapy.

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Renewable energy enables sensor networks with the capability to recharge and provide perpetual data services. Due to low recharging rates and the dynamics of renewable energy such as solar and wind power, providing services without interruptions caused by battery runouts is non-trivial. Most environment monitoring applications require data collection from all nodes at a steady rate. The objective of this paper is to design a solution for fair and high throughput data extraction from all nodes in presence of renewable energy sources. Specifically, we seek to compute the lexicographically maximum data collection rate for each node, such that no node will ever run out of energy. We propose a centralized algorithm and an asynchronous distributed algorithm that can compute the optimal lexicographic rate assignment for all nodes. The centralized algorithm jointly computes the optimal data collection rate for all nodes along with the flows on each link, while the distributed algorithm computes the optimal rate when the routes are pre-determined. We prove the optimality for both the centralized and the distributed algorithms, and use a testbed with 155 sensor nodes to validate the distributed algorithm.