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NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke.

ABSTRACT: Blocking axonal growth inhibitor NogoA has been of great interest for promoting axonal recovery from neurological diseases. The present study investigates the therapeutic effects of blocking NogoA, inducing functional recovery and promoting white matter repair in an experimental animal model of stroke. Adult male rats were subjected to white matter injury by subcortical ischemic stroke. Twenty-four hours after surgery, 250 ug of anti-NogoA or anti-IgG-1 were administered through the tail vein. The quantity of NogoA protein was determined by immunohistochemistry in the brain and peripheral organs. In addition, functional status, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers were analyzed. Moreover, an in vitro study was performed in order to strengthen the results obtained in vivo. A lower quantity of NogoA protein was found in the brain and peripheral organs of the animals that received anti-NogoA treatment. The animals receiving anti-NogoA treatment showed significantly better results in terms of functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group at 28 days. White matter integrity was in part restored by antibody-mediated inhibition of NogoA administration in those animals that were subjected to an axonal injury by subcortical stroke. This white matter restoration triggered functional recovery.

SUBMITTER: Otero-Ortega L

PROVIDER: S-EPMC5573364 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke.

Otero-Ortega Laura L Gómez-de Frutos Mari Carmen MC Laso-García Fernando F Sánchez-Gonzalo Alba A Martínez-Arroyo Arturo A Díez-Tejedor Exuperio E Gutiérrez-Fernández María M

Scientific reports 20170825 1

Blocking axonal growth inhibitor NogoA has been of great interest for promoting axonal recovery from neurological diseases. The present study investigates the therapeutic effects of blocking NogoA, inducing functional recovery and promoting white matter repair in an experimental animal model of stroke. Adult male rats were subjected to white matter injury by subcortical ischemic stroke. Twenty-four hours after surgery, 250 ug of anti-NogoA or anti-IgG-1 were administered through the tail vein. T ...[more]

PMID: 28842591

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Project description:BackgroundUnilateral spatial neglect (USN) is common and associated with poor motor and cognitive outcomes as well as impaired quality of life following stroke. Traditionally, the neural substrates underlying USN have been thought to be cortical areas, such as the posterior parietal cortex. However, patients with stroke involving only subcortical structures may also present with USN. While only a few studies have reported on USN in subcortical stroke, the involvement of white matter tracts related to brain networks of visuospatial attention is one possible explanation for subcortical neglect. Therefore, this study aimed to investigate which specific white matter tracts are neural substrates for USN in patients with subcortical stroke.MethodsTwenty-two patients with subcortical stroke without cortical involvement who were admitted to the Department of Rehabilitation Medicine at Seoul National University Bundang Hospital were retrospectively enrolled. Nine subjects were subclassified into a "USN(+)" group, as they had at least two positive results on three tests (the Schenkenberg line bisection test, Albert's test, and house drawing test) and a score of 1 or higher on the Catherine Bergego scale. The remaining 13 subjects without abnormalities on those tests were subclassified into the "USN(-)" group. Stroke lesions on MRI were manually drawn using MRIcron software. Lesion overlapping and atlas-based analyses of MRI images were conducted. The correlation was analyzed between the overlapped lesion volumes with white matter tracts and the severity of USN (in the Albert test and the Catherine Bergego scale).ResultsLesions were more widespread in the USN(+) group than in the USN(-) group, although their locations in the right hemisphere were similar. The atlas-based analyses identified that the right cingulum in the cingulate cortex, the temporal projection of the superior longitudinal fasciculus, and the forceps minor significantly overlapped with the lesions in the USN(+) group than in the USN(-) group. The score of the Catherine Bergego scale correlated with the volume of the involved white matter tracts.ConclusionIn this study, white matter tracts associated with USN were identified in patients with subcortical stroke without any cortical involvement. Our study results, along with previous findings on subcortical USN, support that USN may result from damage to white matter pathways.

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NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke.

Publications

NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke.

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