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Bilbao, Euskal Herria
Teacher of Anatomy in the University of the Basque Country. Current research field: role of astrocytes in acquired epilepsy.

Saturday, 3 November 2007

Acquired epilepsy: identifying the guilty.

Epilepsy is a chronic disease characterized by spontaneous recurrent seizures, which are caused by thousands of neurons firing together. Acquired epilepsy is associated to previous brain injury and comprises 3 stages: i) the acute phase is associated to an episode of brain injury, ii) the lantecy or asymptomantic phase, and iii) chronic epilepsy is characterized by spontaneous chornic seizures [Pitkanen & Sutula, 2002].
Increases of intracellular calcium concentration ([Ca2+]i) in the acute phase underly all types of acquired epilepsy. Long lasting changes in response to injury would lead to the formation of epileptic foci, composed of neurons with a lowered firing threshold and prolonged excitatory postsynaptic potential [Hause & Hesdorffer, 1990; Pitkanen & Sutula, 2002; Delorenzo et al., 2005].
It has been theroized during decades that a astroglial disfunction may play a role in the progression from the acute to the chornic state of epilepsy, but few authors have proposed astrocytes as a therapeutic target. Initialy, the glial hypothesis was based on the correlation observed between the intensity of the astrocytic reaction after lesions such as trauma or stroke and the probability for the onset of chronic epilepsy.
The current knowledge on astrocyte physiology and pathophysiology of epilepsy point at reactive astrocytes as major therapeutic targets for the treatment of chronic epilepsy
[Anderson and Swanson, 2000; Amiry-Moghaddam et al., 2003; Allen & Barres, 2005; Halassa et al, 2007; Landmark, 2007; Lee et al., 2007; Lively and Brown, 2007]. Thus, astrocytes participate in three functions which are known to be altered in chronic epilepsy: 1) potasium homeostasis, 2) control of glutamatergic activity, 3) regulation of synaptogenesis.
The question arises whether astrocytes should be considered a major therapeutic target for acquired epilepsy.