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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 in ~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, ?-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 pro-cognitive 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.

SUBMITTER: Shetty AK

PROVIDER: S-EPMC3250288 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

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Progress in cell grafting therapy for temporal lobe epilepsy.

Shetty Ashok K AK

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20111001 4

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 in ~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 b ...[more]

PMID: 21892793

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Project description:Doublecortin (DCX) is widely regarded as a marker of immature and migrating neurons during development. While DCX expression persists in adults, particularly in the temporal lobe and neurogenic regions, it is unknown how seizures influence its expression. The aim of the present study was to explore the distribution and characteristics of DCX-expressing cells in surgical and postmortem samples from 40 adult and paediatric patients, with epilepsy and with or without hippocampal sclerosis (HS), compared to post mortem controls. The hippocampus (pes and body), parahippocampal gyrus, amygdala, temporal pole and temporal cortex were examined with DCX immunohistochemistry using four commercially-available DCX antibodies, labelled cells were quantified in different regions of interest as well as their co-expression with cell type specific markers (CD68, Iba1, GFAP, GFAP?, nestin, SOX2, CD34, OLIG2, PDGFR?, NeuN) and cell cycle marker (MCM2). Histological findings were compared with clinical data, as well as gene expression data obtained from the temporal cortex of 83 temporal lobe epilepsy cases with HS. DCX immunohistochemistry identified immature (Nestin-/NeuN-) neurons in layer II of the temporal neocortex in patients with and without epilepsy. Their number declined significantly with age but was not associated with the presence of hippocampal sclerosis, seizure semiology or memory dysfunction. DCX+ cells were prominent in the paralaminar nuclei and periamygdalar cortex and these declined with age but were not significantly associated with epilepsy history. DCX expressing cells with ramified processes were prominent in all regions, particularly in the hippocampal subgranular zone, where significantly increased numbers were observed in epilepsy samples compared to controls. DCX ramified cells co-expressed Iba1, CD68 and PDGFR?, and less frequently MCM2, OLIG2 and SOX2, but no co-localization was observed with CD34, nestin or GFAP/GFAP ?. Gene expression data from neocortical samples in patients with TLE and HS supported ongoing DCX expression in adults. We conclude that DCX identifies a range of morphological cell types in temporal lobe epilepsy, including immature populations, glial and microglial cell types. Their clinical relevance and biological function requires further study but we show some evidence for alteration with age and in epilepsy.

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Progress in cell grafting therapy for temporal lobe epilepsy.

Publications

Progress in cell grafting therapy for temporal lobe epilepsy.

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