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NeuroMolecular Medicine

, Volume 21, Issue 4, pp 484–492 | Cite as

Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia

  • Chinthasagar Bastian
  • Jerica Day
  • Stephen Politano
  • John Quinn
  • Sylvain Brunet
  • Selva BaltanEmail author
Original Paper
  • 250 Downloads

Abstract

Stroke significantly affects white matter in the brain by impairing axon function, which results in clinical deficits. Axonal mitochondria are highly dynamic and are transported via microtubules in the anterograde or retrograde direction, depending upon axonal energy demands. Recently, we reported that mitochondrial division inhibitor 1 (Mdivi-1) promotes axon function recovery by preventing mitochondrial fission only when applied during ischemia. Application of Mdivi-1 after injury failed to protect axon function. Interestingly, L-NIO, which is a NOS3 inhibitor, confers post-ischemic protection to axon function by attenuating mitochondrial fission and preserving mitochondrial motility via conserving levels of the microtubular adaptor protein Miro-2. We propose that preventing mitochondrial fission protects axon function during injury, but that restoration of mitochondrial motility is more important to promote axon function recovery after injury. Thus, Miro-2 may be a therapeutic molecular target for recovery following a stroke.

Keywords

Mitochondria Miro-2 NOS3 Mitochondrial dynamics Ischemia Stroke 

Notes

Acknowledgements

This work was supported by Grants from NIA (AG033720) to S.B and NINDS (NS094881) to S.B and S.B. We thank Christopher Nelson, PhD for his editorial assistance.

Funding

This work was supported by Grants from NIA (AG033720) to S.B and NINDS (NS094881) to S.B and S.B.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical Approval

All experimental procedures were performed according to the principles of the Guide for the Care and Use of Laboratory Animals (National Association for Biomedical Research) and approved by The Institutional Animal Care and Use Committee (IACUC) of the Cleveland Clinic. Experimental procedures were performed and reported in compliance with the ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments).

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Authors and Affiliations

  1. 1.Department of Neurosciences, Lerner Research InstituteCleveland Clinic FoundationClevelandUSA

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