This indicates that a supply of exoge nous DAF would be necessary to protect neurons scientific assays from hypoxic ischemia insults. Discussion Two major questions have been addressed in this study. First, does the presence of soluble DAF attenuate neu ronal damage induced by the chemical hypoxic condi tions Second, how does DAF protect neurons from the hypoxia mediated injury The results demonstrate that treatment Inhibitors,Modulators,Libraries with DAF protects cellular function and increases cell viability in a cultured neuronal chemical hypoxia model. DAF decreases complement activation and distribution. Inhibitors,Modulators,Libraries Furthermore, this protective effect of DAF is associated with the ability to directly inhibit com plement activation and suppress Src tyrosine kinase and caspase signaling pathways.

Cyanide is a toxic chemical that has been used as a weapon Inhibitors,Modulators,Libraries of war and also as means of terrorist attacks on civilian populations. It inhibits the respiratory chain, blocking the utilization of oxygen and affecting mito chondrial function. Neurons are particularly vulner able to energy deprivation. Inhibitors,Modulators,Libraries Therefore, one of the main target organ system of cyanide toxicity is the central nervous system. NaCN treatment, which mimics acute hypoxic cell damage, is commonly used as an experimen tal model to study hypoxia in vitro. This model is generally used to measure neuronal viability and pro vides a means to measure metabolic stress and mitochon drial dysfunction as it relates to excitability of neurons. In addition, NaCN has been used to elucidate mech anisms of ischemic preconditioning and screen for potential neuroprotective compounds drugs.

Here we used NaCN combined with glucose deprivation to mimic a hypoxic ischemic environment in order to inves tigate the effects of DAF on neuronal injury and to explore the potential mechanisms of DAF associated with neuroprotection. Electrophysiological changes caused by Inhibitors,Modulators,Libraries hypoxic isch emic conditions are an early sign of neuronal injury and indicator of the degree of injury. Data recorded dur ing cell recovery in normal medium showed that neither NaCN nor DAF changed cortical cell excitability in our model. Spontaneous neuronal electrical activity is critical for many aspects of developmental processes at all stages, such as central axon growth, navigation, and pruning of inappropriate connections.

We used glutamatergic AMPA and NMDA mediated spontaneous plateau depolarization potentials and burst firing as an index to study neural network activities. The addition of NaCN significantly reduced neuronal spontaneous plateau potential and MG132 burst firing whereas DAF reversed these effects. This finding demonstrates that DAF promotes recovery of neuronal network dysfunction induced by hypoxia. Dendritic spines are micron sized protrusions of the dendritic membrane that serve as the postsynaptic com ponent for the vast majority of central nervous system excitatory and inhibitory synapses.