RAPID ALTERATION OF TAU IN OLIGODENDROCYTES AFTER FOCAL ISCHEMIC-INJURY IN THE RAT - INVOLVEMENT OF FREE-RADICALS

Glial inclusions containing the microtubule-associated protein tau are present in a variety of chronic neurodegenerative conditions. We now report a rapid and time-dependent increase of tau immunoreactivity wit hin oligodendrocytes after focal cerebral ischemia in the rat. The num ber of tau positive oligodendrocytes in the ipsilateral subcortical wh ite matter increased six- to eightfold by 40 minutes after permanent m iddle cerebral artery occlusion (MCAO). Tau was detected using antibod ies that label both the N- and C-terminal of the protein, suggesting a ccumulation of full-length protein within these cells. Pretreatment wi th the spin trap agent alpha-phenyl-tea-butyl-nitrone (PBN)(100mg/kg) reduced the number of tau-positive oligodendrocytes by 55% in the subc ortical white matter of the ischemic hemisphere compared with untreate d animals at 40 minutes after MCAO. In contrast, pretreatment with glu tamate receptor antagonists MK-801 (0.5 mg/kg) or -dihydroxy-6-nitro-7 -sulpfamoylbenzo(f)quinoxaline (NBQX) (2 x 30 mg/kg), failed to reduce the number of tau-positive oligodendrocytes after 40 minutes of ische mia. The results indicate that oligodendrocytes respond rapidly to an ischemic challenge and that free radical-mediated mechanisms are invol ved in the cascade leading to increased tau immunoreactivity.