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Neuroquímica de la epilepsia, neurotransmisión inhibitoria y modelos experimentales: nuevas perspectivas

2006; Viguera Publishers; Volume: 42; Issue: 03 Linguagem: Inglês

10.33588/rn.4203.2005674

1576-6578

Carlos de Cabo, P Hernández, Ana Prieto Martín,

Epilepsy research and treatment

The biological mechanisms of epilepsy allow pathophysiological patterns to be established which are essential for the selection of new therapeutic targets. The identification of these mechanisms also provides us with knowledge about the dynamics of neuronal arrangement, synaptogenesis, synaptic transmission and the receptors involved, and even the development of the brain.Recent advances in neurobiology regarding the GABAergic system point to it as playing a leading role in the pathophysiology of epilepsy. We evaluate the different functional formats of the ionotropic (GABAA) and metabotropic (GABAB) gamma-aminobutyric (GABA) receptors. Although the main function posited is inhibitory, owing to the variability of their location, subunits and neuronal physiology/maturation they can even end up expressing excitatory functions. We discuss the anomalies in the GABAergic system identified in animal models with epilepsy and in brain tissue samples from patients submitted to surgery due to epilepsy. The mechanism inhibiting the activation of GABA receptors is performed by hyperpolarisation achieved by entry of Cl- into the neuron--a process mediated by the cotransporter KCC2, typically expressed in the neuron. Mutations in the KCC2 gene produce mice that are susceptible to seizures. In some animal models it has been found that loop diuretics (furosemide) suppress seizures. Mutations in genes that code for ion channels have been identified in numerous epileptic syndromes and this pushes epilepsy ever further inside the broad group of disorders known as channelopathies. The origin could be polygenetic in many cases.The GABAergic system seems to situate itself as the main system implicated in the pathophysiology of epilepsy, although conditions that have been considered to be idiopathic up till now could have a polygenic nature.