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Investigation of hypoxia‐inducible factor‐1α in hippocampal sclerosis: A postmortem study
Author(s) -
Feast Alexandra,
Martinian Lillian,
Liu Joan,
Catarino Claudia B.,
Thom Maria,
Sisodiya Sanjay M.
Publication year - 2012
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2012.03591.x
Subject(s) - hippocampal sclerosis , epilepsy , hippocampal formation , vascular endothelial growth factor , hypoxia (environmental) , neuroprotection , medicine , neuroscience , colocalization , pathology , endocrinology , psychology , vegf receptors , chemistry , temporal lobe , organic chemistry , oxygen
Summary 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.