Acute motor deficit and subsequent remyelination‐associated recovery following internal capsule demyelination in mice
| Autor: | Nobuhiko Ohno, Jeffrey K. Huang, Reiji Yamazaki |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Internal capsule Central nervous system Biochemistry lysophosphatidylcholine Lesion Mice 03 medical and health sciences Cellular and Molecular Neuroscience Myelin 0302 clinical medicine Internal Capsule medicine Animals Remyelination Myelin Sheath Molecular Basis of Disease Endothelin-1 Microglia business.industry Macrophages Multiple sclerosis Lysophosphatidylcholines Recovery of Function medicine.disease Immunohistochemistry Axons Mice Inbred C57BL Motor Skills Disorders Stroke motor recovery Oligodendroglia remyelination 030104 developmental biology medicine.anatomical_structure Original Article demyelination ORIGINAL ARTICLES medicine.symptom Motor Deficit business 030217 neurology & neurosurgery Demyelinating Diseases |
| Zdroj: | Journal of Neurochemistry |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.15142 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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