Limits...
Beneficial compaction of spinal cord lesion by migrating astrocytes through glycogen synthase kinase-3 inhibition.

Renault-Mihara F, Katoh H, Ikegami T, Iwanami A, Mukaino M, Yasuda A, Nori S, Mabuchi Y, Tada H, Shibata S, Saito K, Matsushita M, Kaibuchi K, Okada S, Toyama Y, Nakamura M, Okano H - EMBO Mol Med (2011)

Bottom Line: This treatment resulted in accelerated migration of reactive astrocytes to sequester inflammatory cells that spared myelinated fibres and significantly promoted functional recovery.A variety of in vitro and in vivo experiments further suggested that GSK-3 inhibition stimulated astrocyte migration by decreasing adhesive activity via reduced surface expression of β1-integrin.Our results reveal a novel benefit of GSK-3 inhibition for SCI and suggest that the stimulation of astrocyte migration is a feasible therapeutic strategy for traumatic injury in the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

Show MeSH

Related in: MedlinePlus

Administration of Ro3303544 reduces demyelination and promotes functional recovery after contusive SCIQuantitative analysis of eriochrome cyanine-positive areas in the ventral white matter at 42 DPI revealed that treatment with Ro3303544 reduced injury-associated demyelination. Data represent mean ± SEM (**p < 0.01, *p < 0.05, n = 5 mice per group). Scale bars: 250 µm.Hindlimb movement evaluated using the Basso mouse scoring scale improved significantly in the Ro3303544 group compared to the control group from 21 DPI. Data represent mean ± SEM. (*p < 0.05, **p < 0.01, ***p < 0.001; 2-way repeated measures ANOVA followed by Bonferroni post hoc test, n = 12 and 13 mice in the control and Ro3303544 groups, respectively.)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3377108&req=5

fig06: Administration of Ro3303544 reduces demyelination and promotes functional recovery after contusive SCIQuantitative analysis of eriochrome cyanine-positive areas in the ventral white matter at 42 DPI revealed that treatment with Ro3303544 reduced injury-associated demyelination. Data represent mean ± SEM (**p < 0.01, *p < 0.05, n = 5 mice per group). Scale bars: 250 µm.Hindlimb movement evaluated using the Basso mouse scoring scale improved significantly in the Ro3303544 group compared to the control group from 21 DPI. Data represent mean ± SEM. (*p < 0.05, **p < 0.01, ***p < 0.001; 2-way repeated measures ANOVA followed by Bonferroni post hoc test, n = 12 and 13 mice in the control and Ro3303544 groups, respectively.)

Mentions: An association between compaction of inflammatory cells by migrating reactive astrocytes and a reduction in delayed neuronal damage, such as demyelination, has been previously reported (Herrmann et al, 2008; Okada et al, 2006). Accordingly, while eriochrome cyanine blue staining revealed severe demyelination, as expected, at the lesion level in the control group at 42 DPI, significantly reduced demyelination was observed in the mice treated with Ro3303544 (Fig 6A).


Beneficial compaction of spinal cord lesion by migrating astrocytes through glycogen synthase kinase-3 inhibition.

Renault-Mihara F, Katoh H, Ikegami T, Iwanami A, Mukaino M, Yasuda A, Nori S, Mabuchi Y, Tada H, Shibata S, Saito K, Matsushita M, Kaibuchi K, Okada S, Toyama Y, Nakamura M, Okano H - EMBO Mol Med (2011)

Administration of Ro3303544 reduces demyelination and promotes functional recovery after contusive SCIQuantitative analysis of eriochrome cyanine-positive areas in the ventral white matter at 42 DPI revealed that treatment with Ro3303544 reduced injury-associated demyelination. Data represent mean ± SEM (**p < 0.01, *p < 0.05, n = 5 mice per group). Scale bars: 250 µm.Hindlimb movement evaluated using the Basso mouse scoring scale improved significantly in the Ro3303544 group compared to the control group from 21 DPI. Data represent mean ± SEM. (*p < 0.05, **p < 0.01, ***p < 0.001; 2-way repeated measures ANOVA followed by Bonferroni post hoc test, n = 12 and 13 mice in the control and Ro3303544 groups, respectively.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377108&req=5

fig06: Administration of Ro3303544 reduces demyelination and promotes functional recovery after contusive SCIQuantitative analysis of eriochrome cyanine-positive areas in the ventral white matter at 42 DPI revealed that treatment with Ro3303544 reduced injury-associated demyelination. Data represent mean ± SEM (**p < 0.01, *p < 0.05, n = 5 mice per group). Scale bars: 250 µm.Hindlimb movement evaluated using the Basso mouse scoring scale improved significantly in the Ro3303544 group compared to the control group from 21 DPI. Data represent mean ± SEM. (*p < 0.05, **p < 0.01, ***p < 0.001; 2-way repeated measures ANOVA followed by Bonferroni post hoc test, n = 12 and 13 mice in the control and Ro3303544 groups, respectively.)
Mentions: An association between compaction of inflammatory cells by migrating reactive astrocytes and a reduction in delayed neuronal damage, such as demyelination, has been previously reported (Herrmann et al, 2008; Okada et al, 2006). Accordingly, while eriochrome cyanine blue staining revealed severe demyelination, as expected, at the lesion level in the control group at 42 DPI, significantly reduced demyelination was observed in the mice treated with Ro3303544 (Fig 6A).

Bottom Line: This treatment resulted in accelerated migration of reactive astrocytes to sequester inflammatory cells that spared myelinated fibres and significantly promoted functional recovery.A variety of in vitro and in vivo experiments further suggested that GSK-3 inhibition stimulated astrocyte migration by decreasing adhesive activity via reduced surface expression of β1-integrin.Our results reveal a novel benefit of GSK-3 inhibition for SCI and suggest that the stimulation of astrocyte migration is a feasible therapeutic strategy for traumatic injury in the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus