title: Pharmacological modulation in mesial temporal lobe epilepsy: Current status and future perspectives.
abstract: Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE. In particular, the link between neuroinflammation, GABAAR and epilepsy has been extensively studied mainly because of the relevant therapeutic implications that the pharmacological modulation of these phenomena would have in the clinical practice. In this review, we briefly summarize the studies that could pave the road to develop new disease-modifying therapeutic strategies for pharmacoresistant MTLE patients. Both clinical observations in human MTLE and experimental findings will be discussed, highlighting the potential modulatory crosstalk between the deregulation of the inhibitory (GABAergic) transmission and the sustained activation of the innate immune response.
authors.affiliation: Institute of Neurology, University Magna Græcia, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council, Catanzaro, Italy. Electronic address: a.gambardella@unicz.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: Institute of Neurology, University Magna Græcia, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council, Catanzaro, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.affiliation: Ri.MED Foundation, Palermo, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Cifelli
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ruffolo
authors.affiliation: Institute of Neurology, University Magna Græcia, Catanzaro, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mumoli
authors.affiliation: Academic Medical Center, Dept. (Neuro)Pathology and Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, Rome, Italy; IRCCS San Raffaele Pisana, Rome, Italy. Electronic address: eleonora.palma@uniroma1.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Palma
mesh_terms: D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy*; D018682:GABA Agents / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
chemical_list: D018682:GABA Agents; D004364:Pharmaceutical Preparations
keywords: AEDs; GABA(A); Hippocampal sclerosis; MTLE; Neuroinflammation