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• W4210266935 abstract "ABSTRACT Damage to long axons in white matter tracts is a major pathology in closed head traumatic brain injury (TBI). Acute TBI treatments are needed that protect against axon damage and promote recovery of axon function to prevent long term symptoms and neurodegeneration. Our prior characterization of axon damage and demyelination after TBI led us to examine repurposing of 4-aminopyridine (4-AP), an FDA-approved inhibitor of voltage-gated potassium (Kv) channels. 4-AP is currently indicated to provide symptomatic relief for patients with chronic stage multiple sclerosis, which involves axon damage and demyelination. We tested clinically relevant dosage of 4-AP as an acute treatment for experimental TBI and found multiple benefits in corpus callosum axons. This randomized, controlled pre-clinical study focused on the first week after TBI, when axons are particularly vulnerable. 4-AP treatment initiated one day post-injury dramatically reduced axon damage detected by intra-axonal fluorescence accumulations in Thy1-YFP mice of both sexes. Detailed electron microscopy in C57BL/6 mice showed that 4-AP reduced pathological features of mitochondrial swelling, cytoskeletal disruption, and demyelination. Furthermore, 4-AP improved the molecular organization of axon nodal regions by restoring disrupted paranode domains and reducing Kv1.2 channel dispersion. 4-AP treatment did not resolve deficits in action potential conduction across the corpus callosum, based on ex vivo electrophysiological recordings at 7 days post-TBI. Thus, this first study of repurposing 4-AP as an acute treatment for TBI demonstrates pre-clinical efficacy in decreasing pathological hallmarks of axon damage. Studies beyond this acute phase are now warranted to assess functional utility and outcome trajectory. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is an acute injury that, if unresolved, can progress to cause persistent, debilitating symptoms. Currently, no treatments effectively prevent damage to long myelinated axons in white matter tracts, which is a hallmark pathology of TBI. 4-aminopyridine (4-AP) is FDA-approved to treat chronic symptoms in patients with multiple sclerosis, which involves autoimmune damage to myelinated axons. As the first assessment of repurposing 4-AP as an acute treatment for TBI, our randomized, controlled studies tested the hypothesis that low-dose 4-AP initiated one day after experimental TBI will reduce acute axon damage and demyelination. We found that 4-AP treatment significantly reduced the progression of axon pathology and demyelination during the first week after TBI using clinically relevant experimental conditions." @default.
• W4210266935 created "2022-02-08" @default.
• W4210266935 creator A5003815469 @default.
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• W4210266935 date "2022-01-28" @default.
• W4210266935 modified "2023-10-18" @default.
• W4210266935 title "Acute Axon Damage and Demyelination are Mitigated by 4-Aminopyridine (4-AP) Therapy after Experimental Traumatic Brain Injury" @default.
• W4210266935 cites W1771974095 @default.
• W4210266935 cites W1790168366 @default.
• W4210266935 cites W1908391790 @default.
• W4210266935 cites W1911071268 @default.
• W4210266935 cites W1971355501 @default.
• W4210266935 cites W1971719199 @default.
• W4210266935 cites W1975813436 @default.
• W4210266935 cites W1977680690 @default.
• W4210266935 cites W1986436947 @default.
• W4210266935 cites W1988723810 @default.
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• W4210266935 cites W1995968640 @default.
• W4210266935 cites W2002433576 @default.
• W4210266935 cites W2005111601 @default.
• W4210266935 cites W2007530842 @default.
• W4210266935 cites W2007743087 @default.
• W4210266935 cites W2012575744 @default.
• W4210266935 cites W2033463506 @default.
• W4210266935 cites W2045167317 @default.
• W4210266935 cites W2045774434 @default.
• W4210266935 cites W2045964757 @default.
• W4210266935 cites W2051575838 @default.
• W4210266935 cites W2055127611 @default.
• W4210266935 cites W2055241344 @default.
• W4210266935 cites W2059237840 @default.
• W4210266935 cites W2060703524 @default.
• W4210266935 cites W2075125615 @default.
• W4210266935 cites W2081557633 @default.
• W4210266935 cites W2081771004 @default.
• W4210266935 cites W2090546414 @default.
• W4210266935 cites W2094827682 @default.
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• W4210266935 cites W2129696399 @default.
• W4210266935 cites W2131876585 @default.
• W4210266935 cites W2131933566 @default.
• W4210266935 cites W2140819328 @default.
• W4210266935 cites W2168013023 @default.
• W4210266935 cites W2169169507 @default.
• W4210266935 cites W2234093367 @default.
• W4210266935 cites W2313452457 @default.
• W4210266935 cites W2318138205 @default.
• W4210266935 cites W2345129398 @default.
• W4210266935 cites W2418835817 @default.
• W4210266935 cites W2549310065 @default.
• W4210266935 cites W2565283532 @default.
• W4210266935 cites W2578054857 @default.
• W4210266935 cites W2594986637 @default.
• W4210266935 cites W2595085771 @default.
• W4210266935 cites W2626915014 @default.
• W4210266935 cites W2746575140 @default.
• W4210266935 cites W2765260668 @default.
• W4210266935 cites W2765467523 @default.
• W4210266935 cites W2767612966 @default.
• W4210266935 cites W2883880076 @default.
• W4210266935 cites W2888223086 @default.
• W4210266935 cites W2896613290 @default.
• W4210266935 cites W2901443920 @default.
• W4210266935 cites W2948839982 @default.
• W4210266935 cites W2967956895 @default.
• W4210266935 cites W2969526404 @default.
• W4210266935 cites W2980757180 @default.
• W4210266935 cites W2991034264 @default.
• W4210266935 cites W2996859213 @default.
• W4210266935 cites W2999894350 @default.
• W4210266935 cites W3015197613 @default.
• W4210266935 cites W3019856991 @default.
• W4210266935 cites W3022053973 @default.
• W4210266935 cites W3041503675 @default.
• W4210266935 cites W3048256465 @default.
• W4210266935 cites W3092863788 @default.
• W4210266935 cites W3129960831 @default.
• W4210266935 cites W3133949059 @default.
• W4210266935 cites W3135352035 @default.
• W4210266935 cites W3135757968 @default.
• W4210266935 cites W3136855296 @default.
• W4210266935 cites W3140720727 @default.
• W4210266935 cites W3150732497 @default.
• W4210266935 cites W3176142945 @default.
• W4210266935 cites W3179083532 @default.
• W4210266935 cites W3181019798 @default.
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• W4210266935 doi "https://doi.org/10.1101/2022.01.27.477989" @default.
• W4210266935 hasPublicationYear "2022" @default.
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