Abstract
We investigate whether Nogo-A is involved in the secondary axonal degeneration in the thalamus after distal middle cerebral artery occlusion (MCAO) in stroke-prone renovascular hypertensive rats (RHRSP). The expression of Nogo-A in ipsilateral ventroposterior nucleus (VPN) of the thalamus in RHRSP was observed at 1, 2 and 4 weeks after distal MCAO. In addition, intracerebroventricular infusion of NEP1-40, a Nogo-66 receptor (NgR) antagonist peptide, was administered starting 24 h after MCAO and continued for 1, 2 and 4 weeks, respectively. Axonal damage and regeneration were evaluated by analysis of the immunoreactivity (IR) of amyloid betaA4 precursor protein (APP), growth associated protein 43 (GAP-43) and microtubule associated protein 2 (MAP-2) in ipsilateral VPN of the thalamus at 1, 2 and 4 weeks after distal MCAO. Following ischemia, the expression of Nogo-A in oligodendrocytes increased persistently and its localization became redistributed around damaged axons and dendrites. Administration of NEP1-40 downregulated the expression of Nogo-A, reduced axonal injury and enhanced axonal regeneration. Our data suggest that Nogo-A is involved in secondary axonal degeneration and that inhibition of Nogo-A can reduce neuronal damage in the thalamus after distal MCAO.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / metabolism
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Axons / pathology
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Biomarkers / metabolism
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Cerebral Infarction / metabolism*
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Cerebral Infarction / pathology
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Cerebral Infarction / physiopathology
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Hypertension / complications*
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Hypertension / physiopathology
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Immunohistochemistry
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Infarction, Middle Cerebral Artery / metabolism
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Infarction, Middle Cerebral Artery / pathology
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Infarction, Middle Cerebral Artery / physiopathology
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Male
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Myelin Proteins / metabolism*
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Myelin Proteins / pharmacology
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Myelin Proteins / therapeutic use
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Nerve Growth Factors / pharmacology
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Nerve Growth Factors / therapeutic use
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Nerve Regeneration / drug effects
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Nerve Regeneration / physiology
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Nerve Tissue Proteins / metabolism
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Nogo Proteins
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Oligodendroglia / metabolism
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Peptide Fragments / pharmacology
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Peptide Fragments / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Retrograde Degeneration / metabolism*
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Retrograde Degeneration / pathology
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Retrograde Degeneration / physiopathology
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Thalamus / metabolism*
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Thalamus / pathology
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Thalamus / physiopathology
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Up-Regulation / physiology
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Ventral Thalamic Nuclei / metabolism
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Ventral Thalamic Nuclei / pathology
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Ventral Thalamic Nuclei / physiopathology
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Wallerian Degeneration / metabolism*
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Wallerian Degeneration / pathology
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Wallerian Degeneration / physiopathology
Substances
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Biomarkers
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Myelin Proteins
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NEP1-40 protein, human
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Nerve Growth Factors
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Nerve Tissue Proteins
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Nogo Proteins
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Peptide Fragments
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RTN4 protein, human
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Rtn4 protein, rat