Title:Aberrant Connection Formation and Glia Involvement in the Progression of Pharmacoresistant
Mesial Temporal Lobe Epilepsy
Volume: 28
Issue: 28
Author(s): Angélica Vega-García, Rosalinda Guevara-Guzmán, Omar García-Gómez, Iris Feria-Romero, Francisca Fernández-Valverde, Mario Alonso-Vanegas and Sandra Orozco-Suárez*
Affiliation:
- Neurological
Diseases Medical Research Unit, Specialty Hospital, “Dr. Bernardo Sepúlveda”, National Medical Center “XXI, Century”, Mexican
Social Security Institute, IMSS, Mexico City, Mexico
Keywords:
Mesial temporal lobe epilepsy, drug resistance, mossy fiber sprouting, hippocampus, cerebral cortex, aberrant connections, astrogliosis.
Abstract: Epilepsy is the most common chronic neurological disease, affecting approximately 65 million
people worldwide, with mesial temporal lobe epilepsy (mTLE) being the most common type, characterized by
the presence of focal seizures that begin in the hippocampus, and subsequently generalize to structures such as
the cerebral cortex. It is estimated that approximately 40% of patients with mTLE develop drug resistance
(DR), whose pathophysiological mechanisms remain unclear. The neuronal network hypothesis is one attempt
to understand the mechanisms underlying resistance to antiepileptic drugs (AEDs), since recurrent seizure
activity generates excitotoxic damage and activation of neuronal death and survival pathways that, in turn,
promote the formation of aberrant neuronal networks. This review addresses the mechanisms that are activated,
perhaps as compensatory mechanisms in response to the neurological damage caused by epileptic seizures, but
that affect the formation of aberrant connections that allow the establishment of inappropriate circuits. On the
other hand, glia seems to have a relevant role in post-seizure plasticity, thus supporting the hypothesis of the
neuronal network in drug-resistant epilepsy, which has been proposed for ELT.
