The kinetic model consists of five compartments and is governed by kinetic mass balance equations with Michaelis-Menten type expressions for reaction rates and transports between the compartments. The neuronal activation BI 10773 is implemented in terms of the effect of neuronal activity on parameters controlling the blood flow and neurotransmitter transport, and a feedback mechanism coupling the glutamate concentration in the synaptic cleft and the ATP hydrolysis, thus accounting for the energetic cost of the membrane potential restoration in the postsynaptic neurons. The changes in capillary volume follow the balloon model

developed for BOLD MRI. The model follows the time course of the saturation levels of the blood hemoglobin, which

link metabolism and BOLD FMRI signal. Analysis of the model predictions suggest that stoichiometry alone is not enough to determine glucose partitioning between neuron and astrocyte. Lactate exchange between neuron and astrocyte is supported by the model predictions, but the uncertainty on the direction and rate is rather elevated. By and large, the model suggests that astrocyte produces and effluxes lactate, while neuron may switch from using to producing lactate. The level of ATP hydrolysis in astrocyte is substantially higher than strictly required for neurotransmitter cycling, in agreement with the literature. (C) 2010 Elsevier Ltd. All rights reserved.”
“Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of severe and permanent AZD3965 concentration neurologic disability after birth. The inducible cyclooxygenase COX-2, which along with COX-1 catalyzes the first committed step in prostaglandin (PG) synthesis, elicits significant brain injury in models of cerebral ischemia; MRIP however its downstream PG receptor pathways trigger both toxic and paradoxically protective effects. Here, we investigated the function of PGE(2) E-prostanoid (EP) receptors in the acute outcome

of hypoxic-ischemic (HI) injury in the neonatal rat. We determined the temporal and cellular expression patterns of the EP1-4 receptors before and after HIE and tested whether modulation of EP1-4 receptor function could protect against cerebral injury acutely after HIE. All four EP receptors were expressed in forebrain neurons and were induced in endothelial cells after HIE. Inhibition of EP1 signaling with the selective antagonist SC-51089 or co-activation of EP2-4 receptors with the agonist misoprostol significantly reduced HIE cerebral injury 24 h after injury. These receptor ligands also protected brain endothelial cells subjected to oxygen glucose deprivation, suggesting that activation of EP receptor signaling is directly cytoprotective. These data indicate that the G-protein coupled EP receptors may be amenable to pharmacologic targeting in the acute setting of neonatal HIE. (C) 2011 Elsevier Ireland Ltd.