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Enhancing axonal myelination: Clemastine attenuates cognitive impairment in a rat model of diffuse traumatic brain injury.
- Source :
-
Translational research : the journal of laboratory and clinical medicine [Transl Res] 2024 Jun; Vol. 268, pp. 40-50. Date of Electronic Publication: 2024 Jan 19. - Publication Year :
- 2024
-
Abstract
- Traumatic brain injury (TBI) has a significant impact on cognitive function, affecting millions of people worldwide. Myelin loss is a prominent pathological feature of TBI, while well-functioning myelin is crucial for memory and cognition. Utilizing drug repurposing to identify effective drug candidates for TBI treatment has gained attention. Notably, recent research has highlighted the potential of clemastine, an FDA-approved allergy medication, as a promising pro-myelinating drug. Therefore, in this study, we aim to investigate whether clemastine can enhance myelination and alleviate cognitive impairment following mild TBI using a clinically relevant rat model of TBI. Mild diffuse TBI was induced using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Animals were treated with either clemastine or an equivalent volume of the vehicle from day 1 to day 14 post-injury. Following treatment, memory-related behavioral tests were conducted, and myelin pathology in the cortex and hippocampus was assessed through immunofluorescence staining and ProteinSimple® capillary-based immunoassay. Our results showed that TBI leads to significant myelin loss, axonal damage, glial activation, and a decrease in mature oligodendrocytes in both the cortex and hippocampus. The TBI animals also exhibited notable deficits in memory-related tests. In contrast, animals treated with clemastine showed an increase in mature oligodendrocytes, enhanced myelination, and improved performance in the behavioral tests. These preliminary findings support the therapeutic value of clemastine in alleviating TBI-induced cognitive impairment, with substantial clinical translational potential. Our findings also underscore the potential of remyelinating therapies for TBI.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Male
Rats
Brain Injuries, Traumatic drug therapy
Brain Injuries, Traumatic pathology
Brain Injuries, Traumatic complications
Brain Injuries, Diffuse drug effects
Brain Injuries, Diffuse pathology
Hippocampus drug effects
Hippocampus pathology
Clemastine pharmacology
Clemastine therapeutic use
Myelin Sheath drug effects
Myelin Sheath pathology
Myelin Sheath metabolism
Disease Models, Animal
Cognitive Dysfunction drug therapy
Cognitive Dysfunction pathology
Axons drug effects
Axons pathology
Rats, Sprague-Dawley
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1810
- Volume :
- 268
- Database :
- MEDLINE
- Journal :
- Translational research : the journal of laboratory and clinical medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38246342
- Full Text :
- https://doi.org/10.1016/j.trsl.2024.01.008