Reversible cyclosporine A sensitive mitochondrial depolarization occurs within minutes of stroke onset in mouse somatosensory cortex in vivo, a two-photon imaging study. The Journal of biological chemistry [J Biol Chem] Journal article | | Title | Reversible cyclosporine A sensitive mitochondrial depolarization occurs within minutes of stroke onset in mouse somatosensory cortex in vivo, a two-photon imaging study. | | Author(s) | Liu RR, Murphy TH | | Institution | Univ. of British Columbia, Canada. | | Source | J Biol Chem 2009 Nov 5. | | Abstract | Neuronal structure and function are rapidly damaged during global ischemia, but can in part recover during reperfusion. Despite apparent recovery in the hours-days following an ischemic episode, delayed cell death can be initiated making it important to understand how initial ischemic events affect potential mediators of apoptosis. Mitochondrial dysfunction and the opening of the mitochondrial permeability transition pore (mPTP) is proposed to link ischemic ionic imbalance to mitochondrially-mediated cell death pathways. Using two-photon microscopy we monitor mitochondrial transmembrane potential (phi M) in vivo within the somatosensory cortex during ischemia and reperfusion in a mouse global ischemia model. Our results indicated a synchronous loss of phi M within 1-3 min of ischemic onset that was linked to within seconds of plasma-membrane potential (phi P) depolarization. Phi M recovered rapidly upon reperfusion and no delayed depolarization was observed over 2 h. Cyclosporine A (CsA) treatment largely blocked phi M collapse during ischemia indicating a role for the mPTP. Blocking phi M depolarization did not affect structural damage to dendrites suggesting that the opening of the mPTP and damage to dendrites are separable pathways that are activated during Phi P depolarization. Our findings using in vivo imaging suggest that mitochondrial dysfunction and specifically the activation of the mPTP are early reversible events during brain ischemia that could trigger delayed cell death. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19892710 |
|
|
| |
Advertise on this site.
| | |
|
