The promise of minocycline in neurology

Yong, V. Wee; Wells, Jennifer; Giuliani, Fabrizio; Casha, Steven; Power, Christopher; Metz, Luanne M.

doi:10.1016/s1474-4422(04)00937-8

Cited by 461 publications

(347 citation statements)

References 62 publications

Supporting

Mentioning

341

Contrasting

Unclassified

Order By: Relevance

“…Microglial cells may contribute to ischemic brain damage by producing pro-inflammatory molecules, reactive oxygen species, and matrix metalloproteinases and may release chemokines, promoting leukocyte infiltration, and leading to secondary injury. 24 It was reported that microglia could exacerbate endothelial cell death after oxygen and glucose deprivation and that treatment with minocycline, a drug known to reduce microglial activation and proliferation, 8 could attenuate this phenomenon. 25 Recombinant tPA induces a catalyticindependent activation of the extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase leading to microglial activation in culture.…”

Section: Discussionmentioning

confidence: 99%

“…5 Infiltrating leukocytes release cytokines and chemokines, which amplify the brain inflammatory response further by causing more extensive activation of resident cells and infiltration of leukocytes, eventually leading to disruption of the blood-brain barrier (BBB), cerebral edema, neuronal cell death, and hemorrhagic transformation. 1 Antiinflammatory strategies in mice and rats have been shown to reduce infarct size, edema, and neurologic deficits, [6][7][8] confirming the deleterious role of leukocytes and innate immune cells in experimental stroke.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Lenglet

Montecucco

Coutts

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The effect of recombinant human tissue plasminogen activator (rtPA) on neuroinflammation after stroke remains largely unknown. Here, we tested the effect of rtPA on expression of cellular adhesion molecules, chemokines, and cytokines, and compared those with levels of inflammatory cell recruitment, brain injury, and mortality over 3 days after transient middle cerebral artery occlusion (MCAO) in mice. Mortality was dramatically increased after rtPA treatment compared with saline treatment during the first day of reperfusion. Among the animals that survived, rtPA significantly increased CCL3 expression, microglia recruitment, and cerebral infarction 6 hours after MCAO. In contrast, the extent of neutrophils and macrophages infiltration in the brain was similar in both saline-and rtPA-treated animals. Recombinant human tissue plasminogen activator induced Il1b and Tnf expression, 6 and 72 hours after MCAO, respectively, and dramatically reduced interleukin 6 (IL-6) level 24 hours after reperfusion. A dose response study confirmed the effect of rtPA on CCL3 and Il1b expressions. The effect was similar at the doses of 1 and 10 mg/kg. In conclusion, we report for the first time that rtPA amplified microglia recruitment early after stroke in association with a rapid CCL3 production. This early response may take part in the higher susceptibility of rtPA-treated animals to reperfusion injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Lenglet

Montecucco

Coutts

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…However, it fails to inhibit muscle pain, a pain condition that does not show any glial activation (Ledeboer et al, 2006). Minocycline, a tetracycline antibiotic, has been used as a microglia inhibitor and shows efficacy in several neurodegenerative conditions (Tikka & Koistinaho, 2001;Yong et al, 2004). Spinal injection of minocycline via intrathecal route was shown to attenuate neuropathic pain at early times but not at late times, suggesting a unique role of microglia in the development of nerve injury-induced neuropathic pain (Ledeboer et al, 2005b;Raghavendra et al, 2003).…”

Section: The Role Of Microglia In Pain Controlmentioning

confidence: 99%

Do glial cells control pain?

Wen²,

et al. 2007

View full text Add to dashboard Cite

Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer's and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not only cause neurodegeneration in these disease conditions, but also cause abnormal pain by acting on spinal cord dorsal horn neurons in injury conditions. Pain can also be potentiated by growth factors such as BDNF and bFGF that are produced by glia to protect neurons. Thus, glia cells can powerfully control pain when they are activated to produce various pain mediators. We will review accumulating evidence supporting an important role of microglia cells in the spinal cord for pain control under injury conditions (e.g. nerve injury). We will also discuss possible signaling mechanisms in particular MAP kinase pathways that are critical for glia control of pain. Investigating signaling mechanisms in microglia may lead to more effective management of devastating chronic pain.

show abstract

“…Minocycline is a second-generation tetracycline that effectively crosses the blood-brain barrier (Yong et al, 2004). In addition to its antibiotic properties, minocycline has been reported to have neuroprotective effects in various experimental models of cerebral ischemia (Yrjanheikki et al, 1999), traumatic brain injury (Sanchez Mejia et al, 2001), amyotrophic lateral sclerosis (ALS) (Zhu et al, 2002), Parkinson's diseases (PD) (Wu et al, 2002), kainic acid treatment (Heo et al, 2006), Huntington's disease (HD) (Chen et al, 2000;Wang et al, 2003), and multiple sclerosis (Popovic et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

Choi

Kim

Shin

et al. 2007

Neuropsychopharmacol

259

179

View full text Add to dashboard Cite

Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood-brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases. In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models. Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNAdependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 a and caspase 12 activation induced by amyloid b peptide 1-42 treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 a were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid b peptide 1-42 -infused rats. We found that minocycline administration attenuated deficits in learning and memory in amyloid b peptide 1-42 -infused rats. Increased phosphorylated state of eukaryotic translation initiation factor-2 a is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity. On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.

show abstract

The promise of minocycline in neurology

Cited by 461 publications

References 62 publications

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Do glial cells control pain?

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

Contact Info

Product

Resources

About