Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

Abstract

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 therapies.

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

“…Clinical and experimental evidence indicates a positive correlation between SRS frequency and neuron loss (Lowenstein, 1996;Ben-Ari and Cossart, 2000). Hence, the search for neuroprotective treatments has become a focus of interest in the study of MTLE due to their possible implications for the prevention of SRS and neuropathological changes (Curia et al, 2014).…”

Context-dependent spatially periodic activity in the human entorhinal cortex

“…Beyond their scientific relevance, the hippocampus and EC are clinically implicated in Alzheimer's disease (5,6), where these structures show the earliest expression of plaques and tangles and concomitant progressive cell death, causing spatial disorientation and spatial memory loss. Coincidentally, the two structures, as part of the mesial temporal lobe, are highly susceptible to epileptic seizure (7). These cells offer a glimpse into how the brain integrates multimodal and movement-dependent sensory inputs and converts them into a coherent environment-referenced neuronal representation.…”

Cortical epileptogenesis of slowly kindled freely moving rats

“…It creates a local (i.e. focal) electrical activation and a slower epileptogenesis that is more characteristic to human TLE [15] and allows to observe both the propagation of the epileptiform discharges and the interictal periods [16].…”