Progress in Cell Grafting Therapy for Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE), exemplified by complex partial seizures, is recognized in~30% of epileptic patients. Seizures in TLE are associated with cognitive dysfunction and are resistant to antiepileptic drug therapy iñ 35% of patients. Although surgical resection of the hippocampus bestows improved seizure regulation in most cases of intractable TLE, this choice can cause lasting cognitive deficiency and reliance on antiepileptic drugs. Thus, alternative therapies that are proficient in both containing the spontaneous recurrent seizures and reversing the cognitive dysfunction are needed. The cell transplantation approach is promising in serving as an adept alternate therapy for TLE, because this strategy has shown the capability to curtail epileptogenesis when used soon after an initial precipitating brain injury, and to restrain spontaneous recurrent seizures and improve cognitive function when utilized after the occurrence of TLE. Nonetheless, this treatment needs further advancement and rigorous evaluation in animal prototypes of chronic TLE before the conceivable clinical use. It is especially vital to gauge the efficacy of distinct donor cell types, such as the hippocampal precursor cells, γ-aminobutyric acid-ergic progenitors, and neural stem cells derived from diverse human sources (including the embryonic stem cells and induced pluripotent stem cells) for longstanding seizure suppression using continuous electroencephalographic recordings for prolonged periods. Additionally, the identification of the mechanisms underlying the graft-mediated seizure suppression and improved cognitive function, and the development of apt grafting strategies that enhance the anti-seizure and procognitive effects of grafts will be necessary. The goal of this review is to evaluate the progress made hitherto in this area and to discuss the prospect for cell-based therapy for TLE.

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer׳s and Parkinson׳s diseases

“…The purpose of this review is to deliberate on recent studies of GABA-ergic cell grafts in prototypes of neurological disorders other than epilepsy, as detailed discussion on the efficacy of GABA-ergic and other cell grafts in epilepsy models is available in several previous review articles (Sebe and Baraban, 2011;Shetty, 2011Shetty, , 2014Tyson and Anderson, 2014). Accordingly, this review confers the promise of GABA-ergic cell therapy for schizophrenia, chronic neuropathic pain, AD and PD.…”

Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis, and epilepsy: Can early neural stem cell grafting intervention provide protection?

“…These include the brain-derived neurotrophic factor (BDNF), the fibroblast growth factor-2 (FGF-2) and the glial cell-line derived neurotrophic factor (GDNF) [14,15,25]. From this perspective, intervention strategies that are efficient for preventing or restraining the progression of the original precipitating injury into memory and mood dysfunction and chronic epilepsy development have immense value [26]. Ideal therapeutic interventions are those capable of promoting normal levels of neurogenesis with apt incorporation of newly generated neurons into the injured hippocampal circuitry.…”

“…Cell therapy using NSCs as donor cells has received great interest as one of the promising therapeutic interventions for restraining hippocampus injury-induced memory and mood dysfunction and chronic TLE development [8,26,31]. This concept is buoyed by multiple characteristics of these cells.…”

“…An ideal interventional treatment strategy applied shortly after an episode of SE should therefore be capable of protecting the left over hippocampal principal neurons and subclasses of GABA-ergic interneurons, diminishing inflammation, adding new GABA-ergic interneurons, maintaining the extent and pattern of hippocampal neurogenesis at normal levels. From these viewpoints, NSC grafting appears promising as a treatment for SE because, NSCs have the potential to release a multitude of neuroprotective factors, suppress inflammation, add new GABA-ergic interneurons, and maintain hippocampal neurogenesis at normal levels through addition of fresh NSCs to the neurogenic niche, stimulation of endogenous NSC proliferation and facilitation of increased neuronal differentiation of the progeny of NSCs [26,31,37,44]. …”

Film‐Based Implants for Supporting Neuron–Electrode Integrated Interfaces for The Brain

“…Brain cell therapy could allow the functional replacement of missing or damaged neurons by transplanting cells that integrate with the host brain [1, 2] . For example, grafts of fetal brain tissues in epileptic patients provide inhibitory neurons for suppressing abnormal seizures [3] . Alternatively, in the field of brain-machine-interfaces, brain electrodes could transmit neuronal signals as artificial circuitry to bypass a lost neuronal connection, such as the corticospinal pathway in a paralyzed patient [4] .…”