Advanced

Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke

Rodhe, Johanna; Burguillos, Miguel A.; de Pablos, Rocio M.; Kavanagh, Edel; Persson, Annette LU ; Englund, Elisabet LU ; Deierborg, Tomas LU ; Venero, Jose L. and Joseph, Bertrand (2016) In Acta neuropathologica communications 4. p.1-11
Abstract

Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression... (More)

Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Caspase-3, Caspase-8, Human brain tissue, Ischemic stroke, Macrophage, Microglia, pMCAO model, Spatio-temporal activation
in
Acta neuropathologica communications
volume
4
pages
1 - 11
publisher
BioMed Central
external identifiers
  • scopus:85019381558
ISSN
2051-5960
DOI
10.1186/s40478-016-0365-9
language
English
LU publication?
yes
id
d8cb376b-159f-405e-9c62-51e1d52dc26f
date added to LUP
2019-06-29 22:59:49
date last changed
2019-09-17 04:57:49
@article{d8cb376b-159f-405e-9c62-51e1d52dc26f,
  abstract     = {<p>Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work. </p>},
  articleno    = {92},
  author       = {Rodhe, Johanna and Burguillos, Miguel A. and de Pablos, Rocio M. and Kavanagh, Edel and Persson, Annette and Englund, Elisabet and Deierborg, Tomas and Venero, Jose L. and Joseph, Bertrand},
  issn         = {2051-5960},
  keyword      = {Caspase-3,Caspase-8,Human brain tissue,Ischemic stroke,Macrophage,Microglia,pMCAO model,Spatio-temporal activation},
  language     = {eng},
  month        = {08},
  pages        = {1--11},
  publisher    = {BioMed Central},
  series       = {Acta neuropathologica communications},
  title        = {Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke},
  url          = {http://dx.doi.org/10.1186/s40478-016-0365-9},
  volume       = {4},
  year         = {2016},
}