Ultrastruktur der Glia- und Axonschädigung durch 6-Aminonicotinamid (6 An) am Sehnerv der Ratte

Light and electron microscopic studies were performed in optic nerves and tracts of 25 adult rats until 21 days following intraperitoneal application of 10 mg/kg 6 AN, an antimetabolite of nicotinamide. The results were: Progressive astrocytic swelling (ER and perinuclear cisternae) in the orbital portion of the optic nerve. The resulting spongy state disappeared within 10–12 days by scar forming and phagocytic fibrous astrocytes. Within 2–6 days mild swelling of the ER in oligodendrocytes occurred together with extreme myelin swelling, probably by splitting of the first inner intraperiod line, leaving the axon unchanged. The resulting spongy state was observed only in the optic tract and the cerebral portion of the nerve. This was followed by myelin break down and axon degeneration in the whole optic nerve; probably the result of both myelin swelling and secondary (Wallerian) degeneration. In the perilaminar portion some special alterations occurred in the third week p.i.: Axonal swelling, remyelination and inner glial processes of myelin sheaths containing glial filaments. The simultaneous application of 10 mg 6 AN and 10 mg nicotinamide per kg produces no detectable pathologic changes. The morphologic changes after the inhibition of the pentose phosphate shunt by 6 AN are considered to represent a glial syndrome in the optic nerve of the rat, i.e. the axonal changes are secondary to glial alterations. The pathomorphogenesis is characterized by a different vulnerability in the orbital and cerebral portion probably due to different glial populations.