Related Experiment Video
Updated: Jun 11, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Evaluation of cyclosporine A in a stroke model in the immature rat brain
Pierre-Louis Leger1, Damien De Paulis, Sonia Branco
1UMR-CNRS 7102, Université P&M Curie-Paris6, 75005 Paris, France.
Abstract:
The effects of ischemia-reperfusion on opening of the mitochondrial permeability transition pore (mPTP) and its blockade in the immature brain are not fully understood. Presently, we evaluated the effect of cyclosporine A (CsA) on cell death and mPTP opening in a model of transient focal ischemia induced by permanent left middle cerebral artery, and homolateral transient common carotid artery occlusion (50 min) in P7 rats. CsA (10mg/kg) was administered 14 h before induction of ischemia and effects were analyzed at 30-40 min and 48 h after reperfusion. CsA administration reduced infarct size, DNA fragmentation and apoptotic bodies, and inflammatory responses in mild but not severe injury. CsA increased the Ca(2+) load required to open the mPTP (78.4 ± 19.2 vs. 50.2 ± 19.9 nmol.mg(-)(1) protein, p < 0.05) in limiting the decoupling of the respiratory chain by unchanged state 3 but reduced state 4, and attenuated early calpain-mediated alpha-spectrin proteolysis. In conclusion, CsA mediates inhibition of mPTP opening and has a tendency to protect immature rat brain against mild ischemic injury. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."
Insights
Cyclosporine A (CsA) shows potential in protecting immature rat brains from mild ischemic injury by inhibiting the mitochondrial permeability transition pore (mPTP) opening, reducing cell death and inflammation.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Ischemia-reperfusion injury impacts the immature brain, with the role of mitochondrial permeability transition pore (mPTP) opening not fully elucidated.
- Understanding the effects of mPTP blockade is crucial for developing neuroprotective strategies.
Purpose of the Study:
- To investigate the neuroprotective effects of cyclosporine A (CsA) in a rat model of transient focal cerebral ischemia.
- To evaluate CsA's impact on cell death, mPTP opening, and inflammatory responses in the immature brain.
Main Methods:
- Transient focal cerebral ischemia was induced in P7 rats via middle cerebral artery occlusion and carotid artery occlusion.
- Cyclosporine A (CsA) was administered 14 hours prior to ischemia, with analyses conducted post-reperfusion.
- Infarct size, DNA fragmentation, apoptosis, inflammatory markers, mitochondrial function, and alpha-spectrin proteolysis were assessed.
Main Results:
- CsA administration significantly reduced infarct size, DNA fragmentation, apoptotic bodies, and inflammatory responses in cases of mild ischemic injury.
- CsA increased the calcium ion (Ca2+) load necessary for mPTP opening.
- CsA limited respiratory chain decoupling and attenuated early calpain-mediated alpha-spectrin proteolysis.
Conclusions:
- CsA effectively inhibits mPTP opening in the immature brain during ischemia-reperfusion.
- CsA demonstrates a protective effect against mild ischemic brain injury in immature rats.
- Further research may explore CsA's therapeutic potential for neonatal hypoxic-ischemic brain injury.
