Acute motor deficit and subsequent remyelination‐associated recovery following internal capsule demyelination in mice

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known t...

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Bibliographic Details
Published in:Journal of neurochemistry 2021-03, Vol.156 (6), p.917-928
Main Authors: Yamazaki, Reiji, Ohno, Nobuhiko, Huang, Jeffrey K.
Format: Article
Language:English
Subjects:
Central nervous system
Damage
Demyelinating diseases
Demyelination
Density
Drug screening
Dystrophy
Endothelin 1
Endothelins
internal capsule
Lesions
Lysophosphatidylcholine
Macrophages
Microglia
motor recovery
Multiple sclerosis
Myelin
Myelination
Original
ORIGINAL ARTICLES
Recovery
remyelination
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Summary:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC‐induced IC damage to that produced by endothelin‐1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post‐lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1‐injected mice at 28 dpl. In contrast, LPC‐injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC‐induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination. In this issue, we examined the effect of focal internal capsule (IC) demyelination on motor behavior in mice. We found that lysophosphatidylcholine (LPC) induced demyelination at the IC resulted in acute asymmetric motor deficit, followed by subsequent remyelination‐associated functional recovery. Our results suggest that IC demyelination is a tractable model for characterizing demyelination and remyelination through behavioral measurements, and may be used to complement future drug discovery efforts for promoting repair in inflammatory demyelinating disorders, such as multiple sclerosis (MS). Images generated with BioRender.
ISSN:0022-3042
1471-4159
DOI:10.1111/jnc.15142