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Published on: January 3, 2025
Effects of monochlorobimane on cerebral ischemia-induced damage to mitochondria
Sayuri Oshikawa1, Keiko Miyake-Takagi, Norio Takagi
1Department of Pharmacology, Tokyo University of Pharmacy & Life Science, Hachioji, Tokyo 192-0392, Japan.
Abstract:
A possible involvement of inhibitory effects of monochlorobimane (MCB) on the opening of mitochondrial permeability transition (MPT) pore in the cerebroprotection against the ischemic brain injury was examined. MCB (1 mM) inhibited the opening of MPT pore in vitro. Sustained cerebral ischemia was induced by injecting 900 microspheres (48 microm in diameter) into the right hemisphere of rats. At 12 to 72 h after microsphere embolism (ME), the mitochondrial activity was determined histochemically by staining cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) of the brain sections. The COX and SDH stainings in the hippocampus were observed intensively in the pyramidal neurons in the CA2-3 and dentate gyrus rather than those in the CA-1 region. The staining was decreased with time after the embolism. Pretreatment with 10 microg/animal MCB 30 min prior to the embolism significantly attenuated the ME-induced reduction in the staining of COX and SDH in the hippocampus, but not in the pariatal cortex. The results suggest that prevention of the opening of MPT pore by MCB may play an important role in the cerebroprotection against cerebral ischemic injury.
Insights
Monochlorobimane (MCB) inhibits mitochondrial permeability transition (MPT) pore opening, offering cerebroprotection against ischemic brain injury. This finding suggests MCB
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Ischemic brain injury is a significant cause of mortality and disability.
- Mitochondrial dysfunction, particularly the opening of the permeability transition pore (MPT), plays a critical role in ischemic brain injury.
- Cerebroprotection strategies often target mitochondrial pathways.
Purpose of the Study:
- To investigate the potential cerebroprotective effects of monochlorobimane (MCB).
- To examine the role of MCB in inhibiting the opening of the mitochondrial permeability transition (MPT) pore.
- To assess MCB's impact on mitochondrial activity following experimental ischemic brain injury.
Main Methods:
- In vitro inhibition of MPT pore opening by MCB.
- Induction of sustained cerebral ischemia in rats using microsphere embolism (ME).
- Histochemical staining for cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) to assess mitochondrial activity in brain sections at various time points post-ME.
Main Results:
- MCB (1 mM) demonstrated in vitro inhibition of MPT pore opening.
- MCB pretreatment significantly attenuated the reduction in COX and SDH staining in the hippocampus following ME.
- The protective effect of MCB was observed in the hippocampus but not the parietal cortex.
Conclusions:
- Inhibition of MPT pore opening by MCB may be a key mechanism for its cerebroprotective effects.
- MCB shows promise as a therapeutic agent for mitigating ischemic brain injury.
- Targeting MPT pore opening represents a viable strategy for cerebroprotection.
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