. Author manuscript; available in PMC: 2011 Jun 30.

Published in final edited form as: Arch Neurol. 2010 Aug 9;67(12):1442–1448. doi: 10.1001/archneurol.2010.191

Table 1.

Results of Experimental Studies on Minocycline Treatment for Neurological Diseases

Animal Model	Dose and Route	Timing	Outcome	Source
Stroke
MCAO	45 mg/kg IP on d 1, then 22.5 mg/kg for 2 d	12 h prior to MCAO, twice daily for 3 d	Reduced infarct volume, inhibited microglial activation, reduced COX-2 expression	Yrjänheikki et al⁹
MCAO	20 or 100 mg/kg IV	60 min after stroke	Low dose improved behavioral function, reduced infarct volume, decreased apoptosis, upregulated BCL-2; high dose increased behavioral deficit, increased infarct volume, increased apoptosis, and suppressed BCL-2 expression	Matsukawa et al⁶
OGD	0.001–100 μM in vitro	1.5–12 h	Low dose increased neuron viability, decreased neuron death, increased BCL-2 expression; high dose decreased neuron and astrocyte viability, increased astrocyte death	Matsukawa et al⁶
Hypoxia-ischemia	45 mg/kg, IP or SC	12 h prior to hypoxia	Decreased infarct volume in rats, increased infarct volume in mice	Tsuji et al¹⁰
Hypoxia-ischemia	45 mg/kg, SC, for 1 d, then 22.5 mg/kg SC for 2 d	Twice per d starting 12 h prior to hypoxia	Increased infarct volume in mice	Tsuji et al¹⁰
Hypoxia-ischemia	135 mg/kg SC for 1 d, then 68 mg/kg for 2 d	Twice per d starting 12 h prior to hypoxia	Increased infarct volume in mice	Tsuji et al¹⁰
Hypoxia-ischemia	45 mg/kg on d 1, then 22.5 mg/kg or 22.5 mg/kg on d 1, then 10 mg/kg IP	1 week, starting 2 h after hypoxia	Decreased white matter injury, decreased microglial activation	Carty et al¹¹
Hypoxia-ischemia	50 mg/kg IP	Every 12 h for 4 d, starting immediately after hypoxia	Reduced white matter injury, reduced microglial activation	Lechpammer et al¹²

Parkinson Disease
MPTP	60, 90, or 120 mg/kg, oral gavage	24 h after MPTP	Reduced neuron death, reduced microglial activation	Du et al¹³
Rotenone	1, 5, 10 μM in vitro	6 d	Decreased neuron death	Radad et al¹⁴
MPTP in monkey	200 mg/kg, oral	2 weeks during MPTP	Increased neuron death, worsened motor symptoms	Diguet et al¹⁵
MPTP	45 or 60 mg/kg IP	Twice per d for 3 d	Increased neuron death, inhibited microglial activation	Yang et al¹⁶
Weaver mutant	60 mg/kg, oral gavage	P10–P24	Decreased neuron death	Peng et al¹⁷

Huntington Disease
3-NP	45 mg/kg IP	5 d during 3-NP	Worsened behavioral function, increased neuron death	Diguet et al¹⁵
R6/2 mice	5 mg/kg IP	Daily	Delayed disease progression, inhibited caspase expression, delayed mortality	Chen et al¹⁸
R6/2 mice	1 or 10 mg/mL in drinking water	Daily	No change in behavioral function, no change in aggregate formation	Smith et al¹⁹
R6/2 mice	5 mg/kg IP with CoQ10	Daily	Improved behavioral function, decreased neuron damage, decreased aggregate formation	Stack et al²⁰
Quinolinic acid injection	50 mg/kg on d 1, 25 mg/kg after, IP	7 or 21 d after injection	Decreased neuron death, decreased microglial activation	Ryu et al²¹

Alzheimer Disease
Tg-SwDI mice	50 mg/kg IP	Every other day for 28 d at 12 mo of age	Decreased microglial activation, decreased IL-6, improved behavioral function	Fan et al²²
APP-tg mice	55 mg/kg in chow	Daily for 3 mo	Improved cognitive performance, decreased microglial activation	Seabrook et al²³

Multiple Sclerosis
EAE	45 mg/kg IP	For 14 d at symptom onset	Decreased clinical scores, decreased T-cell infiltration	Nikodemova et al²⁴

Amyotropic Lateral Sclerosis
SOD1 mice	10 mg/kg IP	Daily starting at 5 wk of age	Delayed disease onset, prolonged survival	Zhu et al²⁵

Abbreviations: 3-NP, nitropropionic acid; CoQ10, coenzyme Q10; COX-2, cyclooxygenase-2; EAE, experimental autoimmune encephalomyelitis; IL, interleukin; IP, intraperitoneal; IV, intravenous; MCAO, middle cerebral artery occlusion; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; OGD, oxygen glucose deprivation; P, postnatal day; SC, subcutaneously; SOD1, superoxide dismutase 1.