Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL/CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators

MB Grosjean, PM Lenzlinger, PF Stahel, I Yatsiv, E Shohami, O Tentz, Thomas K Kossmann, Maria Morganti-Kossmann

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Abstract

Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas ( CD95) and Fas ligand ( FasL/ CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/ lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury ( CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation ( terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick end- labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co- localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine(-/-) and wild- type mice.
Original languageEnglish
Pages (from-to)235 - 250
Number of pages16
JournalHistology and Histopathology
Volume22
Issue number3
Publication statusPublished - 2007

Cite this

@article{abb31afb6fc54dd395936e14ecf04fc5,
title = "Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL/CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators",
abstract = "Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas ( CD95) and Fas ligand ( FasL/ CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/ lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury ( CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation ( terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick end- labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co- localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine(-/-) and wild- type mice.",
author = "MB Grosjean and PM Lenzlinger and PF Stahel and I Yatsiv and E Shohami and O Tentz and Kossmann, {Thomas K} and Maria Morganti-Kossmann",
year = "2007",
language = "English",
volume = "22",
pages = "235 -- 250",
journal = "Histology and Histopathology",
issn = "0213-3911",
publisher = "Universidad de Murcia",
number = "3",

}

Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL/CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators. / Grosjean, MB; Lenzlinger, PM; Stahel, PF; Yatsiv, I; Shohami, E; Tentz, O; Kossmann, Thomas K; Morganti-Kossmann, Maria.

In: Histology and Histopathology, Vol. 22, No. 3, 2007, p. 235 - 250.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL/CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators

AU - Grosjean, MB

AU - Lenzlinger, PM

AU - Stahel, PF

AU - Yatsiv, I

AU - Shohami, E

AU - Tentz, O

AU - Kossmann, Thomas K

AU - Morganti-Kossmann, Maria

PY - 2007

Y1 - 2007

N2 - Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas ( CD95) and Fas ligand ( FasL/ CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/ lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury ( CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation ( terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick end- labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co- localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine(-/-) and wild- type mice.

AB - Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas ( CD95) and Fas ligand ( FasL/ CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/ lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury ( CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation ( terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick end- labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co- localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine(-/-) and wild- type mice.

UR - http://www.hh.um.es/Abstracts/Vol_22/22_3/22_3_235.htm

M3 - Article

VL - 22

SP - 235

EP - 250

JO - Histology and Histopathology

JF - Histology and Histopathology

SN - 0213-3911

IS - 3

ER -