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Cellular injury and neuroinflammation in children with chronic intractable epilepsy

OBJECTIVE: To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients wh...

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Autores principales: Choi, Jieun, Nordli, Douglas R, Alden, Tord D, DiPatri, Arthur, Laux, Linda, Kelley, Kent, Rosenow, Joshua, Schuele, Stephan U, Rajaram, Veena, Koh, Sookyong
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811703/
https://www.ncbi.nlm.nih.gov/pubmed/20021679
http://dx.doi.org/10.1186/1742-2094-6-38
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author Choi, Jieun
Nordli, Douglas R
Alden, Tord D
DiPatri, Arthur
Laux, Linda
Kelley, Kent
Rosenow, Joshua
Schuele, Stephan U
Rajaram, Veena
Koh, Sookyong
author_facet Choi, Jieun
Nordli, Douglas R
Alden, Tord D
DiPatri, Arthur
Laux, Linda
Kelley, Kent
Rosenow, Joshua
Schuele, Stephan U
Rajaram, Veena
Koh, Sookyong
author_sort Choi, Jieun
collection PubMed
description OBJECTIVE: To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery. METHODS: Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases. RESULTS: Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy. CONCLUSIONS: Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.
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spelling pubmed-28117032010-01-27 Cellular injury and neuroinflammation in children with chronic intractable epilepsy Choi, Jieun Nordli, Douglas R Alden, Tord D DiPatri, Arthur Laux, Linda Kelley, Kent Rosenow, Joshua Schuele, Stephan U Rajaram, Veena Koh, Sookyong J Neuroinflammation Research OBJECTIVE: To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery. METHODS: Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases. RESULTS: Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy. CONCLUSIONS: Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy. BioMed Central 2009-12-19 /pmc/articles/PMC2811703/ /pubmed/20021679 http://dx.doi.org/10.1186/1742-2094-6-38 Text en Copyright ©2009 Choi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Choi, Jieun
Nordli, Douglas R
Alden, Tord D
DiPatri, Arthur
Laux, Linda
Kelley, Kent
Rosenow, Joshua
Schuele, Stephan U
Rajaram, Veena
Koh, Sookyong
Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title_full Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title_fullStr Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title_full_unstemmed Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title_short Cellular injury and neuroinflammation in children with chronic intractable epilepsy
title_sort cellular injury and neuroinflammation in children with chronic intractable epilepsy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811703/
https://www.ncbi.nlm.nih.gov/pubmed/20021679
http://dx.doi.org/10.1186/1742-2094-6-38
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