Background: In 2005, we reported 3 patients with bilateral optic nerve damage early in life. These patients had stable vision for decades but then experienced significant bilateral vision loss with no obvious cause. Our hypothesis, novel at that time, was that the late decline of vision was due to age-related attrition of retinal ganglion cells superimposed on a reduced neuronal population due to the earlier injury.
Evidence Acquisition: The field of epigenetics provides a new paradigm with which to consider the normal aging process and the impact of neuronal injury, which has been shown to accelerate aging. Late-in-life decline in function after early neuronal injury occurs in multiple sclerosis due to dysregulated inflammation and postpolio syndrome. Recent studies by our group in mice have also demonstrated the possibility of partial reversal of cellular aging and the potential to mitigate anatomical damage after injury and even improve visual function.
Results: The results in mice and nonhuman primates published elsewhere have shown enhanced neuronal survival and visual function after partial epigenetic reprogramming.
Conclusions: Injury promotes epigenetic aging , and this finding can be observed in several clinically relevant scenarios. An understanding of the epigenetic mechanisms at play opens the opportunity to restore function in the nervous system and elsewhere with cellular rejuvenation therapies. Our earlier cases exemplify how reconsideration of previously established concepts can motivate inquiry of new paradigms.
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http://dx.doi.org/10.1097/WNO.0000000000002041 | DOI Listing |
J Ethnopharmacol
December 2024
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:
Ethnopharmacological Relevance: Delayed tissue-type plasminogen activator (t-PA) thrombolysis, which has a restrictive therapeutic time window within 4.5 h following ischemic stroke (IS), increases the risk of hemorrhagic transformation (HT) and subsequent neurotoxicity. Studies have shown that the NLRP3 inflammasome activation reversely regulated by the PGC-1α leads to microglial polarization and pyroptosis to cause damage to nerve cells and the blood-brain barrier.
View Article and Find Full Text PDFLife Sci
December 2024
School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, PR China; Southeast Research Institute, Lanzhou University, Lanzhou 730000, PR China. Electronic address:
Objectives: The Shh pathway may shed new light on developing new cell death inhibitors for the therapy of ischemic stroke. We aimed to examine whether the Shh co-reporter SMO or its agonist halcinonide can upregulate Bcl-2 to suppress neuronal cell death, ultimately improving behavioral deficits and reducing cerebral infarction in an ischemic stroke model.
Methods: Halcinonide or genetic manipulation of SMO was conducted in PC12 cells to examine their impacts on oxidative or OGD/R stress, and the chemical, along with AAV-SMO or AAV-EGFP were tested in MCAO rats to investigate their potential protective effects against neuronal damages due to cerebral I/R injury.
J Physiol
December 2024
Division of Reconstructive and Plastic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
The frequent poor functional outcomes after delayed surgical repair of injured human peripheral nerves results in progressive downregulation of growth-associated genes in parallel with reduced neuronal regenerative capacity under each of the experimental conditions of chronic axotomy of neurones that remain without target contact, chronic distal nerve stump denervation, and chronic muscle denervation. Brief (1 h) low-frequency (20 Hz) electrical stimulation (ES) accelerates the outgrowth of regenerating axons across the surgical site of microsurgical repair of a transected nerve. Exercise programmes also promote nerve regeneration with the combination of ES and exercise being the most effective.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Alterations to the composition and function of neuronal nuclear pore complexes (NPCs) have been documented in multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Moreover, recent work has suggested that injury to the NPC can at least in part contribute to TDP-43 loss of function and mislocalization, a pathological hallmark of ALS and related neurodegenerative diseases. Collectively, these studies highlight a role for disruptions in NPC homeostasis and surveillance as a significant pathophysiologic event in neurodegeneration.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, China. Electronic address:
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