Additional Table 4.
Preclinical studies of minocycline plus N-acetylcysteine
| Study | Rigor | Species | Model | Time to first dose, dose | Outcomes |
|---|---|---|---|---|---|
| Abdel Baki, 2009 | Randomization, NS; Blinded, NS | Rat, Male,250–300g | Moderate CCI, Sham-CCI | 45mg/kg MINO, 150 mg/kg NAC 1h, 1d, 2d | 8–23 d spaced APA, Entrances ↑ 8–23dspaced APA, Time to first entrance ↑ 14 d Myelin ↑ |
| Rat, Male,250–300g | Moderate CCI, Sham-CCI | 45mg/kg MINO, 150 mg/kg NAC 3hpreinjury | 1 h IL-1b ↑ | ||
| Haber,2013 | Randomization, NS; Blinding, NS | Rat,250–300g | Moderate CCI, sham-CHI-saline, CCI-saline, | 45mg/kg MINO, 150 mg/kgNAC1h, 1d, 2d | 7 d Conflict APA, Entrances ↑ 8-23dSpaced APA, Time to first entrance ↑ 2 d MP/MG ↑ 2 d Glial fibrillary acid protein ↑ |
| Haber,2018 | Randomization, yes; Blinding, no | Rat,Male,250–300g | Moderate CCI, Sham-CCI, CCI-saline | 45mg/kg MINO, 150 mg/kgNAC1h, 1d, 2d | 14 d Myelin ↑ 1–4dOligodendrocytes ↑ 14 d Oligodendrocyte apoptosis ↑ 4 d MP/MG activation ↑y7 d MP/MG activation ↑ CD86 expression ↑ |
| Sangobowale,2018a | Randomization, yes; Blinded, yes | Rat, Male,250–300g | Moderate CCI, Sham-CCI, CCI-saline | 22.5mg/kg MINO, 75mg/kg NAC 6hfollowed by 1dand 2d | 7 d BM ↑ 7 d APA entrances 6H dosing ↑ 7 d APA time to first entrance ↑ 14 d Hippocampal MAP2 ↑ |
| 22.5mg/kg MINO, 75mg/kg NAC 12 followed by 2dand 3d | 7 d BM ↑ 7 d APA Entrances ↑ 7 d APA Time to first entrance ↑ 14 d Hippocampal MAP2 ↑ 14 d Myelin ↑ |
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| 22.5mg/kg MINO, 75mg/kg NAC 1d, 2dand 3d | 7 d BM ↑ 7 d APA Entrances → 7 d APA Time to first entrance → 14 d Hippocampal MAP2 ↑ 14 d Myelin content → |
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| Mouse, Male,28–30g | Moderate CHI, Sham-CHI, CHI-saline | 22.5mg/kg MINO, 75mg/kg NAC 12h, by 2dand 3d | 7 d BM ↑ 7 d APA, Entrances ↑ 7 d APA Time to first entrance → 14 d Hippocampal MAP2 ↑ 14 d Myelin ↑ |
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| 22.5mg/kg MINO, 75mg/kg NAC 1d, 2 d and 3d | 7 d BM ↑ 7 d APA, Entrances → 7 d APA, Time to first entrance ↑ 14 d Hippocampal MAP2 ↑ 14 d Myelin ↑ |
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| Sangobowale,2018b | Randomization, yes; Blinded, yes | Mouse, Male,28–30g | Moderate CHI, Sham-CHI, CHI-saline | 22.5mg/kg MINO, 75mg/kg NAC 12h, by 2dand 3d | 2–14 d Oligodendrocytes ↑ 14 d oligodendrocyte apoptosis ↑ |
| Whitney, 2021 | Randomization, yes; Blinded, yes | Mouse, Male,28–30g | Moderate CHI, Sham-CHI, CHI-saline | 22.5mg/kgMINO, 75mg/kgNAC3d, 4d, 5d | 7 d BM ↑ 7 d BM probe trial ↑ 14dContralesional CA3 size, number, complexity ↑ 14dIpsilateralCA1 size, number, complexity ↑ 14 d CA1 synapse density ↑ |
Rigor for each study is provided following by the, species, injury model plus severity and control groups, MINO plus NAC dosing. Time after injury is followed by whether MINO plus NAC improved (↑) or had no difference (→) in the experimental outcome. APA: Active place avoidance; BM: Barnes maze; CCI: controlled cortical injury; CHI: closed head injury; MG: macrophage/microglia; MINO: minocycline; MWM: Morris water maze; NAC: N-acetylcysteine; NS: not specified.