Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?
G. Curia, C. Lucchi, J. Vinet, F. Gualtieri, C. Marinelli, A. Torsello, L. Costantino and G. Biagini
Affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Laboratorio di Epilettologia Sperimentale, Universita di Modena e Reggio Emilia, Via Campi, 287, 41125 Modena, Italy.
Keywords: Antiepileptic drug, astrocyte, blood-brain barrier, ghrelin, growth hormone secretagogue, hippocampus, mesial
temporal lobe epilepsy, microglia, neuroinflammation, piriform cortex.
Temporal lobe epilepsy (TLE) is frequently associated with hippocampal sclerosis, possibly caused by a primary
brain injury that occurred a long time before the appearance of neurological symptoms. This type of epilepsy is
characterized by refractoriness to drug treatment, so to require surgical resection of mesial temporal regions involved in
seizure onset. Even this last therapeutic approach may fail in giving relief to patients. Although prevention of hippocampal
damage and epileptogenesis after a primary event could be a key innovative approach to TLE, the lack of clear data on
the pathophysiological mechanisms leading to TLE does not allow any rational therapy. Here we address the current
knowledge on mechanisms supposed to be involved in epileptogenesis, as well as on the possible innovative treatments
that may lead to a preventive approach. Besides loss of principal neurons and of specific interneurons, network rearrangement
caused by axonal sprouting and neurogenesis are well known phenomena that are integrated by changes in receptor
and channel functioning and modifications in other cellular components. In particular, a growing body of evidence
from the study of animal models suggests that disruption of vascular and astrocytic components of the blood-brain barrier
takes place in injured brain regions such as the hippocampus and piriform cortex. These events may be counteracted by
drugs able to prevent damage to the vascular component, as in the case of the growth hormone secretagogue ghrelin and
its analogues. A thoroughly investigation on these new pharmacological tools may lead to design effective preventive
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