Table 6.
Minocycline
| Paper | Animal model and injury model | Intervention and timing | Experimental groups |
Reported outcomes: • Histologic/biochemical/physiological • Behavioral |
|---|---|---|---|---|
| Marchand Eur J Pain2008 |
Model: Adult Male Wistar Rats, 220–250 g Injury: T13 Left Hemisection |
Minocycline IP • 40 mg/kg @ 30 min PI, then 3 times q12 h. |
• SCI + Minocycline (n = 8) Saline IP (n = 8) Sham operated + Minocycline IP (n = 8) Saline IP (n = 8) |
Histologic/Biochemical/Physiological: Minocycline significantly attenuated microglial activation by 30-50% in the lumbar dorsal horns (OX-42 expression, n = 4) and evoked neuronal activity (c-Fos expression after noxious stimulation, n = 4) at 7d and 14d PI. Behavioral: Minocycline treatment prevented the development of mechanical allodynia and thermal hyperalgesia in both ispilateral and contralateral paws during first 2 w PI. |
| Ha Eur Spine J2008 |
Model: Male SD Rats, 300–350 g Injury: T9/10 NYU Impactor 10 g × 25 mm |
Minocycline IP • 30 mg/kg @ 30min PI, then 12 h, 24 h, 36 h and 48 h PI Methylprednisolone IP • 30 mg/kg IP, @ 30 min, then at 12h and 24 h PI |
• SCI + Minocycline (n = 8) MP (n = 8) Saline IV (n = 8) |
Histologic/Biochemical/Physiological: Minocycline decreased lesion volume, attenuated microglial activation (anti-OX-42+ cells) and apoptosis (TUNEL). Behavioral: Minocycline significantly improved locomotor function at 7d PI (2.6 ± 0.5 vs. 1.0 for saline and 2.4 ± 0.5 for MP group in 6-point locomotion scale) and also improved incline plane test score at 7d PI. |
| Pinzon Brain Res2008 |
Model: Male SD Rats, 220–280 g Injury: T9/10 NYU Impactor 10 g × 12.5 mm |
Minocycline IP or IV • 90 mg/kg @ 0h PI, then 45 mg/kg IP at 12h and 24h PI |
• SCI + Minocycline IP (n = 15) Minocycline IV (n = 15) Vehicle IP (n = 8) Vehicle IV (n = 7) |
Histologic/Biochemical/Physiological: Minocycline did not improve spared tissue areas or total cavity areas as calculated from horizontal sections. Behavioral: Minocycline did not lead to behavioral improvement at any point in time (BBB: minocycline IP 12.1 ± 0.18 vs saline control 11.8 ± 0.2; differences in BBB subscores were also not observed). |
| Saganová Neurosci Lett2008 |
Model: Adult Wistar Rats 300–330 g Injury: T9 Balloon Compression (12.5μl × 5 min) |
Minocycline IP • 90 mg/kg @ 1h PI, then 45 mg/kg IP at 12h and 24h • 90 mg/kg @ 1h PI, then 45 mg/kg IP q12h × 5 days |
SCI + Minocycline × 1 day Minocycline × 5 days Saline IP (n = 12/group) |
Histologic/Biochemical/Physiological: Minocycline at both the 1 and 5 day administration regimen increased gray and white matter sparing in sections 2-4 mm rostral to injury epicenter, but did not influence tissue sparing at the epicenter or at any sections caudal to epicenter. Behavioral: Minocycline at both the 1 and 5 day administration regimen did not result in any BBB improvement over 28 days of observation. |
| Yune J Neurosci2007 |
Model: Male SD Rats, 250–300 g Injury: T9/10 NYU Impactor 10 g × 25 mm |
Minocycline IP • 90 mg/kg @ 0h or 2h PI, then 45 mg/kg q12h for 3d. Methylprednisolone IP: • 30 mg/kg @ 0h or 2h PI, then 30 mg/kg q12h for 3d. |
• SCI + Minocycline (n = 44) MP (n = 20) Vehicle (n = 44) Sham (n = 3) |
Histologic/Biochemical/Physiological: Minocycline significantly reduced levels of pro-NGF by 5 d post-SCI, protein levels of p-p38MAPK and p-MAPKAPK-2 by 3d and 5d post-SCI, significantly inhibited p75NTR mRNA and protein, and GTP-bound RhoA at 3d and 5d, significantly decreased the number of caspase-3-positive (CC1-positive) oligodendrocytes, all while sparing myelin and reducing axonal loss. Behavioral: Minocycline treatment (immediate or 2h delay) but not MP resulted in significantly improved BBB, inclined plane and grid walk stepping. Delayed (2 h) minocycline also improved foot coordination (foot print analysis), whereas MP did not. |
| Festoff J Neurochem2006 |
Model: Female SD Rats, 300–325 g Injury: T9 NYU Impactor 10 g × 25 mm |
• Minocycline IP Single dose 90 mg/kg @ 30min, 1h or 24 h PI. 3 doses of 30 mg/kg @ 30min, 1h and 24 h PI. Tetracycline IP 30 mg/kg @ 1 h PI. |
SCI + Minocycline (90 mg/kg @ 0.5,1 or 24 h post-SCI) (n = 12) Minocycline (30 mg/kg × 3) (n = 4) Tetracycline (n = 3) Sham (n not indicated) |
Histologic /Biochemical/Physiological: Minocycline significantly spares tissue, reduces tissue damage, cavity size, gliosis, necrosis, apoptosis, caspase-3 activation and caspase-3 cleavage products. Minocycline also reduced microglial activation and TNF-α levels. Behavioral: Minocycline 30 mg/kg × 3 doses yielded ∼5 point BBB improvement over tetracycline controls. Similarly, minocycline (single dose 90 mg/kg) given at 0.5, 1, or 24 h post-SCI improved BBB scores over tetracycline-treated injured controls (Day 28: 14.6 ± 0.62 vs 8.33 ± 0.66). Timing of minocycline post-injury did not significantly affect functional recovery. |
| Stirling J Neurosci 2004 |
Model: Adult Wistar Rats Injury: Spinal Cord Dorsal Column C7/C8 Transection |
Minocycline IP • 50 mg/kg @ 30 min PI and 8 h PI, then q12 × 2d |
SCI + Minocycline Saline n = 6-8/group for 7d survival n = 4-5/group for 14d survival |
Histologic/Biochemical/Physiological: Minocycline greatly reduces active caspase-3-positive oligodendrocytes and microglia/macrophages profiles in proximal and distal ascending sensory tracts (AST), inhibited transection-induced glial cell death within the distal and proximal AST, reduced ED1-positive (microglial/macrophage) density 7d PI, and reduced corticospinal tract dieback and lesion size both 7d and 14d PI. Behavioral: Footprint analysis revealed improved interlimb coordination and reduced hindlimb angle of rotation with minocycline treatment. |
| Teng PNAS2004 |
Model: Female SD Rats, 280–330g Injury: T9 NYU Impactor 10g × 25 mm |
Minocycline IP • 8, 90 or 180 mg/kg @ 1h PI, collected @ 4h PI (dose response study) • 90 mg/kg @ 1h PI, then 45 mg/kg q12h × 5d |
• SCI + Minocycline Vehicle n = 3/group/dose and time point) |
Histologic/Biochemical/Physiological: A dose-dependent effect of minocycline on cytochrome c release at SCI site was seen at 4h PI, reducing cytochrome c release to the negligible pre-SCI level. At 28d PI, minocycline perserved residual white matter, protected ventral horn neurons and oligodendrocytes, and reduced reactive astroglia within the ventral funiculi. Behavioral: Minocycline-treated rats demonstrated significantly increased coordinated hindlimb motor function; 3w and 4w BBB scores were significantly greater for minocycline treatments vs. vehicle. |
| Lee J Neurotrauma 2003 |
Model: SD Rats, 230-250 g Injury: T10 NYU Impactor 10g × 12.5 mm |
Minocycline IP • 90 mg/kg @ 0h PI, then 45 mg/kg q12 h × 2 doses |
SCI + Minocycline (n = 41) Vehicle (n = 41) Sham (n = 13) |
Histologic/Biochemical/Physiological: Minocycline reduced cavitation between 28 and 38 days, caspase-3 activity, TUNEL-postive cells, and DNA laddering. Behavioral: Minocycline significantly increased BBB scores at 24 - 38 days PI (18.6 ± 0.7 vs. 15.6 ± 0.5). |
| Wells Brain2003 |
Model: Male CD-1 Mice ∼3 months of age Injury: T3/T4 Clip Compression 8 g |
Minocycline IP • 50 mg/kg @ 1 h PI, then 25 mg/kg q24 h × 6 d. |
• SCI + Minocycline (n = 43) Vehicle (n = 41) |
Histologic/Biochemical/Physiological: Minocycline treatment yielded increased rubrospinal tracts, and reduced lesion area. Behavioral: Minocycline improved murine survival, BBB and inclined plane. |
SCI: spinal cord injury; d: day, days; h: hour, hours; w: week, weeks; PI: post-injury; q24h: interval 24 hours;
T8: thoracic vertebra 8; C5: cervical vertebra 5; IP: intraperitoneal; IV: intravenous; SC: subcutaneous;
BBB: Basso, Beattie and Bresnahan locomotor test; MP: Methylprednisolone; SD rats: Sprague-Dawley rats; TNF: tumor necrosis factor.