title: Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury.
abstract: Oxidative stress is generated in several peripheral nerve injury models. In response to oxidative stress, the transcription factor Nrf2 is activated to induce expression of antioxidant responsive element (ARE) genes. The role of Nrf2 in peripheral nerve injury has not been studied to date. In this study, we used a sciatic nerve crush model to examine how deletion of Nrf2 affects peripheral nerve degeneration and regeneration. Our study demonstrated that functional recovery in the Nrf2(-/-) mice were impaired compared to the wild type mice after sciatic nerve crush. Larger myelin debris were present in the distal nerve stump of the Nrf2(-/-) mice than in the wild type mice. The presence of larger myelin debris in the Nrf2(-/-) mice coincides with less macrophages accumulation in the distal nerve stump. Less accumulation of macrophages may have contributed to slower clearance of myelin and thus resulted in the presence of larger myelin debris. Meanwhile, axonal regeneration is comparatively lower in the Nrf2(-/-) mice than in the wild type mice. Even after 3months post the injury, more thinly myelinated axon fibers were present in the Nrf2(-/-) mice than in the wild type mice. Taken collectively, these data support the concept of therapeutic intervention with Nrf2 activators following nerve injury.
authors: School of Pharmacy, University of Wisconsin-Madison, WI 53705, USA.
authors: Linxia
authors: L
authors: Zhang
authors: Delinda
authors: D
authors: Johnson
authors: Jeffrey A
authors: JA
authors: Johnson
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000473:pathology*; D020127:Recovery of Function / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse