{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:54:05Z","timestamp":1791399245109,"version":"4.3.3"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,3,23]],"date-time":"2009-03-23T00:00:00Z","timestamp":1237766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to investigate the role of voltage\u2010dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Calcium ion (Ca<jats:sup>2+<\/jats:sup>) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese\u2010enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N\u2010type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using \u03c9\u2010conotoxin GVIA, an N\u2010type specific blocker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that pathological Ca<jats:sup>2+<\/jats:sup>influx into ONs during optic neuritis is mediated via N\u2010type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of \u03b1<jats:sub>1B<\/jats:sub>, the pore\u2010forming subunit of N\u2010type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages\/activated microglia, and lower levels were detected on astrocytes. The relevance of N\u2010type VDCCs for inflammation\u2010induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with \u03c9\u2010conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages\/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We conclude that N\u2010type VDCCs play an important role in inflammation\u2010induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca<jats:sup>2+<\/jats:sup>influx into the axons; and second, they contribute to macrophage\/microglia function, thereby promoting secondary axonal damage. 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