Adult Neurogenesis in Mesial Temporal Lobe Epilepsy: A Review of Recent Animal and Human Studies

Liu, Y.W.J.; Mee, Edward; Bergin, Peter; Teoh, H. Heng; Connor, Bronwen; Dragunow, Michael; Faull, Richard L.M.

doi:10.2174/138920107780906504

Cited by 16 publications

(1 citation statement)

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“…Another factor to consider is the potential impact of epileptic pathology on the process of neurogenesis, as the majority of our cultured brain tissues were obtained from temporal lobectomies for the treatment of mesial temporal lobe epilepsy. At least in animal models, epileptic development can largely be divided into two phases; acute, which accounts for the first couple of months after the initial seizure generating insult, and chronic, which accounts for the period succeeding the acute phase of the disease [65]. These distinct phases have very differing effects on neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

et al. 2012

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The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5–6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments.

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Section: Discussionmentioning

confidence: 99%

Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

et al. 2012

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The Use of Connexin-Based Therapeutic Approaches to Target Inflammatory Diseases

O’Carroll

Becker

Davidson

et al. 2013

Methods in Molecular Biology

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Alterations in Connexin43 (Cx43) expression levels have been shown to play a role in inflammatory processes including skin wounding and neuroinflammation. Cx43 protein levels increase following a skin wound and can inhibit wound healing. Increased Cx43 has been observed following stroke, epilepsy, ischemia, optic nerve damage, and spinal cord injury with gap junctional communication and hemichannel opening leading to increased secondary damage via the inflammatory response. Connexin43 modulation has been identified as a potential target for protection and repair in neuroinflammation and skin wound repair. This review describes the use of a Cx43 specific antisense oligonucleotide (Cx43 AsODN) and peptide mimetics of the connexin extracellular loop domain to modulate Cx43 expression and/or function in inflammatory disorders of the skin and central nervous system. An overview of the role of connexin43 in inflammatory conditions, how antisense and peptide have allowed us to elucidate the role of Cx43 in these diseases, create models of diseases to test interventions and their potential for use clinically or in current clinical trials is presented. Antisense oligonucleotides are applied topically and have been used to improve wound healing following skin injury. They have also been used to develop ex vivo models of neuroinflammatory diseases that will allow testing of intervention strategies. The connexin mimetic peptides have shown potential in a number of neuroinflammatory disorders in ex vivo models as well as in vivo when delivered directly to the injury site or when delivered systemically.

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Elevated Expression of VEGF-C and Its Receptors, VEGFR-2 and VEGFR-3, in Patients with Mesial Temporal Lobe Epilepsy

et al. 2016

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Mesial temporal lobe epilepsy (MTLE) is a frequent form of focal intractable epilepsy in adults. We previously reported overexpression of vascular endothelial growth factor C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, in epilepsy-associated tuberous sclerosis complex. To identify whether VEGF-C and its receptors are involved in epileptogenesis of MTLE, we investigated the levels and expression pattern of VEGF-C and its receptors in temporal neocortex and hippocampus (HPC) from 28 patients with MTLE and ten control (CTX) subjects. Real-time quantitative polymerase chain reaction and Western blotting results revealed upregulated mRNA and immunoreactive protein levels of VEGF-C, VEGFR-2, and VEGFR-3 in the MTLE group compared to the control groups. Immunohistochemistry and double-labeled immunofluorescence showed that VEGF-C was highly expressed in neurons and astrocytes, including reactive astrocytes and vascular endothelial cells, VEGFR-2 was expressed at a high level in reactive astrocytes and vascular endothelial cells, but not in neurons, whereas VEGFR-3 was only overexpressed in reactive astrocytes. Taken together, these findings suggest that VEGF-C and its receptors, VEGFR-2 and VEGFR-3, may contribute to the epileptogenesis of MTLE.

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Adult Neurogenesis in Mesial Temporal Lobe Epilepsy: A Review of Recent Animal and Human Studies

Cited by 16 publications

References 0 publications

Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

The Use of Connexin-Based Therapeutic Approaches to Target Inflammatory Diseases

Elevated Expression of VEGF-C and Its Receptors, VEGFR-2 and VEGFR-3, in Patients with Mesial Temporal Lobe Epilepsy

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