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The temperature dependence and involvement of mitochondria permeability transition and caspase activation in damage to organotypic hippocampal slices following in vitro ischemia.

Rytter, Anna LU ; Cardoso, Carla M P; Johansson, Petra; Cronberg, Tobias LU ; Hansson, Magnus LU ; Mattiasson, Gustav LU ; Elmer, Eskil LU and Wieloch, Tadeusz LU (2005) In Journal of Neurochemistry 95(4). p.1108-1117
Abstract
The aggravating effect of hyperglycemia on ischemic brain injury can be mimicked in a model of in vitro ischemia (IVI) using murine hippocampal slice cultures. Using this model, we found that the damage in the CA1 region following IVI in the absence or presence of 40 mM glucose (hyperglycemia) is highly temperature dependent. Decreasing the temperature from 35 to 31 degrees C during IVI prevented cell death, whereas increasing the temperature by 2 degrees C markedly aggravated damage. As blockade of the mitochondrial permeability transition (MPT) is equally effective as hypothermia in preventing ischemic cell death in vivo, we investigated whether inhibition of MPT or of caspases was protective following IVI. In the absence of glucose, the... (More)
The aggravating effect of hyperglycemia on ischemic brain injury can be mimicked in a model of in vitro ischemia (IVI) using murine hippocampal slice cultures. Using this model, we found that the damage in the CA1 region following IVI in the absence or presence of 40 mM glucose (hyperglycemia) is highly temperature dependent. Decreasing the temperature from 35 to 31 degrees C during IVI prevented cell death, whereas increasing the temperature by 2 degrees C markedly aggravated damage. As blockade of the mitochondrial permeability transition (MPT) is equally effective as hypothermia in preventing ischemic cell death in vivo, we investigated whether inhibition of MPT or of caspases was protective following IVI. In the absence of glucose, the MPT blockers cyclosporin A and MeIle(4)-CsA but not the immunosuppressive compound FK506 diminished cell death. In contrast, following hyperglycemic IVI, MPT blockade was ineffective. Also, the pan-caspase inhibitor Boc-Asp(OMe)fluoromethyl ketone did not decrease cell death in the CA1 region following IVI or hyperglycemic IVI. We conclude that cell death in the CA1 region of organotypic murine hippocampal slices following IVI is highly temperature dependent and involves MPT. In contrast, cell death following hyperglycemic IVI, although completely prevented by hypothermia, is not mediated by mechanisms that involve MPT or caspase activation (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
neuroprotection, mitochondria, apoptosis, hyperglycemia, temperature, hippocampal slice culture, organotypic
in
Journal of Neurochemistry
volume
95
issue
4
pages
1108 - 1117
publisher
Wiley-Blackwell
external identifiers
  • wos:000232850000018
  • pmid:16144540
  • scopus:28244437805
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2005.03420.x
language
English
LU publication?
yes
id
632249db-8386-4591-9420-9dc74dc20b30 (old id 143834)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16144540&dopt=Abstract
date added to LUP
2007-07-17 08:50:42
date last changed
2017-01-01 07:26:36
@article{632249db-8386-4591-9420-9dc74dc20b30,
  abstract     = {The aggravating effect of hyperglycemia on ischemic brain injury can be mimicked in a model of in vitro ischemia (IVI) using murine hippocampal slice cultures. Using this model, we found that the damage in the CA1 region following IVI in the absence or presence of 40 mM glucose (hyperglycemia) is highly temperature dependent. Decreasing the temperature from 35 to 31 degrees C during IVI prevented cell death, whereas increasing the temperature by 2 degrees C markedly aggravated damage. As blockade of the mitochondrial permeability transition (MPT) is equally effective as hypothermia in preventing ischemic cell death in vivo, we investigated whether inhibition of MPT or of caspases was protective following IVI. In the absence of glucose, the MPT blockers cyclosporin A and MeIle(4)-CsA but not the immunosuppressive compound FK506 diminished cell death. In contrast, following hyperglycemic IVI, MPT blockade was ineffective. Also, the pan-caspase inhibitor Boc-Asp(OMe)fluoromethyl ketone did not decrease cell death in the CA1 region following IVI or hyperglycemic IVI. We conclude that cell death in the CA1 region of organotypic murine hippocampal slices following IVI is highly temperature dependent and involves MPT. In contrast, cell death following hyperglycemic IVI, although completely prevented by hypothermia, is not mediated by mechanisms that involve MPT or caspase activation},
  author       = {Rytter, Anna and Cardoso, Carla M P and Johansson, Petra and Cronberg, Tobias and Hansson, Magnus and Mattiasson, Gustav and Elmer, Eskil and Wieloch, Tadeusz},
  issn         = {1471-4159},
  keyword      = {neuroprotection,mitochondria,apoptosis,hyperglycemia,temperature,hippocampal slice culture,organotypic},
  language     = {eng},
  number       = {4},
  pages        = {1108--1117},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {The temperature dependence and involvement of mitochondria permeability transition and caspase activation in damage to organotypic hippocampal slices following in vitro ischemia.},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2005.03420.x},
  volume       = {95},
  year         = {2005},
}