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Minocycline plus N-acetylcysteine protect oligodendrocytes when first dosed 12 hours after closed head injury in mice

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The mouse closed head injury (CHI) model of traumatic brain injury (TBI) produces widespread demyelination. Myelin content is restored by minocycline (MINO) plus n-acetylcysteine (NAC) or MINO alone when first… Click to show full abstract

The mouse closed head injury (CHI) model of traumatic brain injury (TBI) produces widespread demyelination. Myelin content is restored by minocycline (MINO) plus n-acetylcysteine (NAC) or MINO alone when first dosed at 12 h after CHI. In a rat controlled cortical impact model of TBl, a first dose of MINO plus NAC one h after injury protects resident oligodendrocytes that induce remyelination. In contrast, MINO less effectively protects oligodendrocytes and remyelination is mediated by oligodendrocyte precursor cell proliferation and differentiation. MINO plus NAC or MINO alone is hypothesized to work similarly in the CHI model as in the controlled cortical impact model even when first dosed at 12-h post-CHI. We tested this hypothesis by examining the time course of the changes in the oligodendrocyte antigenic markers CC1, 2',3'-Cyclic-nucleotide 3'-phosphodiesterase and phospholipid protein between 2 and 14 days post-CHI in mice treated with saline, NAC, MINO or MINO plus NAC. CHI produced a long-lasting loss of these markers that was not altered by NAC treatment. In contrast, oligodendrocyte marker expression was maintained by MINO plus NAC between 2 and 14 days post-injury. MINO alone did not prevent the early loss of oligodendrocyte markers, but marker expression significantly increased by 14-days post-injury. These data suggest that MINO plus NAC or MINO alone when first dosed 12 h after CHI increase myelin content using similar mechanisms seen when first dosed 1 h after closed head injury. These data also suggest that drugs protect oligodendrocytes with a clinically useful therapeutic time window.

Keywords: head injury; closed head; mino plus; mino; first dosed; injury

Journal Title: Neuroscience Letters
Year Published: 2018

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