Electrophysiological recordings made in these slices show that in a significant percentage of neurons, GABA has a depolarizing action because of an accumulation of chloride in neurons and thus a different gradient for chloride.60 Indeed, GABA excites neurons in the epileptic network; this is expected to lead to major changes in the operation of the network, since inhibitory GABA plays a central role in the generation of oscillations. This property Inhibitors,research,lifescience,medical also illustrates

yet another property of networks in degenerative disorders: the return to immature properties. Indeed, in all developing brain structures and animal species, there is a higher [C1]i, a property that appears to have been preserved throughout evolution.61,62 The consequence is that GABA excites immature neurons, generating sodium and calcium action potentials and producing a large calcium influx that underlies the trophic actions of GABA on developing neurons.63 There are several indications that after insults of different types, the neurons recuperate or return to their immature situation, at least as far as Inhibitors,research,lifescience,medical some signals are concerned, with the expression of various factors only found during development: “epileptogenesis recapitulates ontogenesis.” These effects are due to a loss of a chloride cotransporter that acts to remove chloride from neurons.64-66 Here again, the genuinely epileptic Inhibitors,research,lifescience,medical tissue

has unique features not found in naive networks. Anoxic insults lead to similar post-traumatic alterations Reactive plasticity is not restricted to epilepsies. Indeed, it has long been recognized that ischemic insult augments the occurrence of seizures and late-onset Inhibitors,research,lifescience,medical epilepsy in humans and in animal models.67-69 A remodeling of neuronal networks also often follows the cell loss produced in CA1pyramidal neurons after a four-vessel occlusion model.70,71 The damage includes various GABAergic interneurons, and is http://www.selleckchem.com/products/AZD0530.html associated with long-term hyperexcitability.53,67 Inhibitors,research,lifescience,medical Electrophysiological recordings of CA3 pyramidal neurons suggest that important morphofunctional reorganization has occurred, and that

this is irreversible.26 Sprouting of mossy fibers has also been documented after ischemic insults,67 as well as an increased glutamatergic activity manifested by a dramatic Carnitine dehydrogenase enhancement of both the frequency of spontaneous glutamatergic EPSCs and that of miniature synaptic currents, suggesting an enhanced quanta! release of glutamate. Therefore, cell loss produces massive modifications of the entire circuit, including neurons that are afferent to the damage and are associated with reorganization of net works. These alterations may then lead to hyperactivity and seizures in the postischemic network, in keeping with the extensive clinical data suggesting postischemic hyperactivity. General implications of these observations The first implication of these observations is that seizures beget seizures.