Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Mar 2007
Bad as a converging signaling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats.
Bad, a proapoptotic Bcl-2 family protein, plays a critical role in determining cell death/survival. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the c-Jun N-terminal kinase (JNK) pathway are thought to be involved in regulation of Bad. Therefore, the present study was performed to clarify the role of Bad as a common target of the PI3-K/Akt and JNK pathways after transient focal cerebral ischemia (tFCI) in rats. ⋯ The present study indicates that signal predominance varies from PI3-K/Akt-mediated survival signaling to JNK-mediated death signaling with the development of neuronal damage in the peripheral area after tFCI. This study also suggests that PI3-K/Akt has a role in Bad inactivation, whereas the JNK pathway is involved in Bad activation. We conclude that Bad may be an integrated checkpoint of PI3-K/Akt-mediated survival signaling and JNK-mediated death signaling and that it contributes to cell fate in the peripheral area after cerebral ischemia.
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J. Cereb. Blood Flow Metab. · Mar 2007
Nonlinear neurovascular coupling in rat sensory cortex by activation of transcallosal fibers.
Functional neuroimaging and normal brain function rely on the robust coupling between neural activity and cerebral blood flow (CBF), that is neurovascular coupling. We examined neurovascular coupling in rat sensory cortex in response to direct stimulation of transcallosal pathways, which allows examination of brain regions inaccessible to peripheral stimulation techniques. Using laser-Doppler flowmetry to record CBF and electrophysiologic recordings of local field potentials (LFPs), we show an exponential relation between CBF responses and summed LFP amplitudes. ⋯ The data suggest that preserved activity of both AMPA and NMDA receptors is necessary for the full CBF response evoked by stimulation of rodent interhemispheric connections. AMPA receptor activation gives rise to a measurable LFP, but NMDA receptor activation does not. The lack of a measurable LFP from neural processes that contribute importantly to CBF may explain some of the difficulties in transforming extracellular current or voltage measurements to a hemodynamic response.