The temperature dependence and involvement of mitochondria permeability transition and caspase activation in damage to organotypic hippocampal slices following in vitro ischemia
| Autor: | Tobias Cronberg, Carla M. P. Cardoso, Tadeusz Wieloch, Eskil Elmér, Anna Rytter, Petra Johansson, Gustav Mattiasson, Magnus Hansson |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Diagnostic Imaging
Programmed cell death Time Factors Caspase 3 Pharmacology Hippocampus Models Biological Biochemistry Neuroprotection Permeability Brain Ischemia Mice Cellular and Molecular Neuroscience Organ Culture Techniques Cyclosporin a medicine Animals Drug Interactions Enzyme Inhibitors Caspase Analysis of Variance Mice Inbred BALB C Cell Death biology Temperature Hypothermia Flow Cytometry Immunohistochemistry Mitochondria Enzyme Activation Animals Newborn Mitochondrial permeability transition pore Apoptosis Caspases Immunology biology.protein Calcium medicine.symptom |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| Popis: | 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 MeIle4-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. |
| Databáze: | OpenAIRE |
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