Neuropathology of SUDEP: role of inflammation, blood-brain barrier impairment, and hypoxia
Neuropathology of SUDEP: role of inflammation, blood-brain barrier impairment, and hypoxia
OBJECTIVE: To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP.
METHODS: Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers.
RESULTS: Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups.
CONCLUSIONS: This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain.
Adolescent, Adult, Biomarkers, Blood-Brain Barrier, Brain, Death, Sudden, Epilepsy, Female, Humans, Hypoxia, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neuroimmunomodulation, Neurons, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
551-561
Michalak, Zuzanna
6396a6ff-f48c-4fef-a528-41420a0c0df5
Obari, Dima
92c4127e-f21e-4491-9a52-8ea367a97b11
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Thom, Maria
a9f63dd8-ba68-4ea1-a945-e4bbd18525d2
Sisodiya, Sanjay M
442600da-eda0-410b-97bb-cde8326d702d
7 February 2017
Michalak, Zuzanna
6396a6ff-f48c-4fef-a528-41420a0c0df5
Obari, Dima
92c4127e-f21e-4491-9a52-8ea367a97b11
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Thom, Maria
a9f63dd8-ba68-4ea1-a945-e4bbd18525d2
Sisodiya, Sanjay M
442600da-eda0-410b-97bb-cde8326d702d
Michalak, Zuzanna, Obari, Dima, Ellis, Matthew, Thom, Maria and Sisodiya, Sanjay M
(2017)
Neuropathology of SUDEP: role of inflammation, blood-brain barrier impairment, and hypoxia.
Neurology, 88 (6), .
(doi:10.1212/WNL.0000000000003584).
Abstract
OBJECTIVE: To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP.
METHODS: Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers.
RESULTS: Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups.
CONCLUSIONS: This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain.
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Accepted/In Press date: 9 November 2016
e-pub ahead of print date: 13 January 2017
Published date: 7 February 2017
Keywords:
Adolescent, Adult, Biomarkers, Blood-Brain Barrier, Brain, Death, Sudden, Epilepsy, Female, Humans, Hypoxia, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neuroimmunomodulation, Neurons, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 428174
URI: http://eprints.soton.ac.uk/id/eprint/428174
ISSN: 0028-3878
PURE UUID: c082fd3a-1e78-4911-8d69-42f92cce8b1e
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Date deposited: 13 Feb 2019 17:30
Last modified: 16 Mar 2024 00:08
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Author:
Zuzanna Michalak
Author:
Dima Obari
Author:
Matthew Ellis
Author:
Maria Thom
Author:
Sanjay M Sisodiya
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