BackgroundThe roles of caspase 3 on the kainic acid-mediated neurodegeneration, dendritic plasticity alteration, neurogenesis, microglial activation and gliosis are not fully understood. Here, we investigate hippocampal changes using a mouse model that receive a single kainic acid-intracerebral ventricle injection. The effects of caspase 3 inhibition on these changes were detected during a period of 1 to 7 days post kainic acid injection.ResultNeurodegeneration was assessed by Fluoro-Jade B staining and neuronal nuclei protein (NeuN) immunostaining. Neurogenesis, gliosis, neuritic plasticity alteration and caspase 3 activation were examined using immunohistochemistry. Dendritic plasticity, cleavvage-dependent activation of calcineurin A and glial fibrillary acidic protein cleavage were analyzed by immunoblotting. We found that kainic acid not only induced neurodegeneration but also arouse several caspase 3-mediated molecular and cellular changes including dendritic plasticity, neurogenesis, and gliosis. The acute caspase 3 activation occurred in pyramidal neurons as well as in hilar interneurons. The delayed caspase 3 activation occurred in astrocytes. The co-injection of caspase 3 inhibitor did not rescue kainic acid-mediated neurodegeneration but seriously and reversibly disturb the structural integrity of axon and dendrite. The kainic acid-induced events include microglia activation, the proliferation of radial glial cells, neurogenesis, and calcineurin A cleavage were significantly inhibited by the co-injection of caspase 3 inhibitor, suggesting the direct involvement of caspase 3 in these events. Alternatively, the kainic acid-mediated astrogliosis is not caspase 3-dependent, although caspase 3 cleavage of glial fibrillary acidic protein occurred.ConclusionsOur results provide the first direct evidence of a causal role of caspase 3 activation in the cellular changes during kainic acid-mediated excitotoxicity. These findings may highlight novel pharmacological strategies to arrest disease progression and control seizures that are refractory to classical anticonvulsant treatment.

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The Internet and World Wide Web represent an increasingly important channel for retail commerce as well as business transactions. However, there are almost 5 billion pages or sites on the Internet and WWW. There lacks an integrated mediator business agent which is around the internet to connect between suppliers and users. Therefore, an intelligent business broking agent between supply and demand is needed for using and sharing the information efficiently and effectively. In this paper we proposed a new business agent architecture. The Business Spy Agent (BSA) captures the supply and demand information from e-commence sites automatically. Supply and Demand Analysis Mechanism (SDAM) uses NLP technologies to extract product and trading information. Domain ontology is used to classify between supply and demand and to divide them into subsets. A benefit model is proposed to handle the pairing between sub-supply and sub-demand. And a divide-and-conquer algorithm is proposed to handle the whole matching between supply and demand. In the negotiation process, the architecture uses NLP and template to produce negotiation text to handle negotiation through mail. Finally, Hidden Business Mining Mechanism (HBMM) adopts data mining technology to achieve hidden business mining. The architecture covers the four process of buying behavior including support and need identification, Product brokering, Merchant brokering, Negotiation.