Investigation of hypoxia-inducible factor-1α in hippocampal sclerosis: A postmortem study

Feast, A., Martinian, L., Liu, J.Y.W., Catarino, C.B., Thom, M. and Sisodiya, S.M. 2012. Investigation of hypoxia-inducible factor-1α in hippocampal sclerosis: A postmortem study. Epilepsia. 53 (8), pp. 1349-1359. https://doi.org/10.1111/j.1528-1167.2012.03591.x

TitleInvestigation of hypoxia-inducible factor-1α in hippocampal sclerosis: A postmortem study
TypeJournal article
AuthorsFeast, A., Martinian, L., Liu, J.Y.W., Catarino, C.B., Thom, M. and Sisodiya, S.M.
Abstract

Purpose: Hypoxia-inducible factor-1α (HIF-1α) is involved in critical aspects of cell survival in response to hypoxia and regulates vascular endothelial growth factor (VEGF) expression. Previous experimental and human studies in epilepsy show up-regulation of VEGF following seizures, although expression of HIF-1α as its potential regulator has not been explored. We used a postmortem (PM) series from patients with epilepsy and hippocampal sclerosis (HS) to investigate patterns of expression of HIF-1α and VEGF and their potential contribution to neuroprotection.

Method: In 33 PMs (17 cases with unilateral HS, 3 with bilateral HS, 3 with No-HS, and 10 controls), we quantified neuronal immunolabeling for HIF-1α and VEGF in hippocampal subfields.

Key Findings: HIF-1α- and VEGF-immunopositive hippocampal neurones were observed in HS, No-HS, and also in control cases; there was no significant difference in overall labeling between epilepsy cases and controls. In positive cases, HIF-1α and VEGF neuronal labeling localized primarily in CA1, CA4, and CA3 subfields in all groups; significantly more positive neurons were seen in the entorhinal cortex in epilepsy cases (p < 0.05). Labeling lateralized to the side of sclerosis in unilateral HS cases, with significant differences between hemispheres (p < 0.05). There was a trend for high HIF-1α labeling scores in patients with Dravet syndrome without HS and sudden unexpected death in epilepsy (SUDEP) cases, and lower scores with long seizure-free periods prior to death. Hippocampal HIF-1α and VEGF labeling showed a significant correlation. There was neuronal colocalization of HIF-1α and VEGF.

Significance: Regional expression patterns are in keeping with seizure-related activation of HIF-1α and VEGF. The prominent expression in non-HS cases could support an overall neuroprotective effect. Correlation between HIF-1α and VEGF neuronal immunolabeling supports HIF-1α–mediated induction of VEGF in epilepsy.

JournalEpilepsia
Journal citation53 (8), pp. 1349-1359
ISSN1528-1167
Year2012
PublisherWiley
Digital Object Identifier (DOI)https://doi.org/10.1111/j.1528-1167.2012.03591.x
Publication dates
Published19 Jul 2012

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