Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Minocycline, a second-generation tetracycline, has been shown to possess neuroprotective effects in animal models of stroke. Pial vessel disruption in adult Wistar rats leads to a cone-shaped cortical lesion and turns into a fluid-filled cavity surrounded by a GFAP+ glia limitans 21 days after injury. This mimics the clinical situation in lacunar infarcts. Minocycline was given intraperitoneally at a dose of 45 mg/kg 1 and 12 h after lesioning, followed by 22.5 mg/kg twice daily until 6 days after lesioning. Control rats received intraperitoneal injections of equivalent volumes of saline. Cavitation was prevented in five out of six minocycline-treated animals and the glia limitans did not appear as the space was filled with GFAP+ reactive astrocytes. However, the number of activated microglia showed no difference between minocycline-treated and -untreated groups. Minocycline did not reduce the number of infiltrating leukocytes, predominately polymorphonuclear neutrophils (PMNs) determined by myeloperoxidase immunoreactivity, or infiltration of CD3+ lymphocytes. The pial vessel occlusion induced a significant upregulation of IL-1beta expression; however, minocycline treatment did not significantly alter this upregulation of IL-1beta. In this study, we found minocycline facilitated the repopulation of the lesion by reactive astrocytes and therefore prevented cavitation; however, we could not identify the molecular signal.
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PMID:Minocycline treatment prevents cavitation in rats after a cortical devascularizing lesion. 1664 93

The absence of effective treatments for stroke presents a critical need for novel strategies that can reduce ischemic injury. Neuroinflammation following focal ischemia induces secondary injury in the region surrounding the insult, thus anti-inflammatory agents are potential neuroprotectants. Minocycline is one such agent possessing neuroprotective properties, however many studies examining minocycline after ischemia have used minimal delays between ischemia and treatment, short survival periods, and lack measures of functional outcome. Such studies do not distinguish whether minocycline provides sustained protection or merely delays cell death. This study was designed to address some of these concerns. Male Sprague-Dawley rats were treated with multiple doses of minocycline (45 mg/kg i.p.) or vehicle beginning 2.5 h after endothelin-1-induced focal ischemia. Measures of forelimb asymmetry and skilled reaching (staircase test) were used to determine functional outcome 7, 15 and 28 days after ischemia. Long-term functional assessment indicates that minocycline provides limited benefit in the staircase test, but confers long-term benefit in the forelimb asymmetry test. Subcortical and whole hemisphere infarct volumes were reduced by 41 and 39% respectively in minocycline-treated animals. Further analysis revealed that minocycline attenuated long-term white matter damage adjacent to the striatal injury core, which correlated with sustained functional benefits. This study indicates that delayed minocycline treatment improves long-term functional outcome which is linked to protection of both white and gray matter.
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PMID:Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia. 1669 Feb 15

We reviewed the results of clinical examinations conducted on and antimicrobial susceptibilities to Neisseria gonorrhoeae isolated from 51 patients with gonococcal urethritis who visited our hospital during the period from February 2005 to April 2006. The type of sexual activity by which the bacteria was transmitted was oral sex in 81.6% (40/49) of the patients, and none of the patients used a condom during oral sex. Fifty percent (24/48) of the patients were aware of the risk of getting sexually transmitted diseases (STDs) from having oral sex without the use of a condom. The ratios of drug-resistant N. gonorrhoeae were 56.9% for Penicillin G, 0% for CVA/Amoxicillin, Azithromycin and Minocycline, 5.9% for Cefpodoxime, 2.0% for Ceftriaxone, 0% for Cefodizime, and 84.4% for Ciprofloxacin, Levofloxacin and Gatifloxacin. The bacteria in 7.8% of the cases were beta-lactamase-producing strains. The results of this study indicated that STD from oral sex is prevalent in Sapporo. Increasing resistance to Quinolone was noted, but levels of susceptibility to other drugs remained relatively high.
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PMID:[Clinical evaluation and antimicrobial susceptibilities of cases of gonococcal urethritis treated in our hospital]. 1756 12

Minocycline reduces infarct volume measured up to 1 week after focal cerebral ischemia, but it has not been shown that this results in lasting improvement in functional outcome. This study examined behavioral outcome in rats out to 3 weeks after focal ischemia induced by injection of the vasoconstrictor endothelin (ET)-1 (400 pmol in 1 microL of saline) into the striatum. Magnetic resonance imaging confirmed reduced blood flow after administration of ET-1, and was used to determine lesion volumes at 1 and 21 days postischemia. In control rats, intraperitoneal injection of minocycline resulted in plasma levels of 6.6 +/- 2.7 microg mL(-1) between 1 and 8 hours after administration. Based on these results, intraperitoneal minocycline treatment was started either 1 hour before or 3 hours after ET-1 administration, and was repeated daily for 5 days. Outcome, assessed using a composite behavioral deficit score (days 2, 4, 7, 14, and 21) and a test of asymmetric forelimb use (days 7 and 21), was significantly better in both groups of rats treated with minocycline, and the improvement was maintained for the 3-week study period. No differences were found in infarct volumes between groups.
J Stroke Cerebrovasc Dis
PMID:Protective effect of minocycline treatment on striatal ischemia. 1790 60

Minocycline is a semi-synthetic, second-generation tetracycline analog which is effectively crossing the blood-brain barrier, effective against gram-positive and -negative infections. In addition to its own antimicrobacterial properties, minocycline has been reported to exert neuroprotective effects over various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment, Huntington' disease and multiple sclerosis. Minocycline has been focused as a neuroprotective agent over neurodegenerative disease since it has been first reported that minocycline has neuroprotective effects in animal models of ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500]. Recently, the effect of minocycline on Alzheimer's disease has been also reported. Although its precise primary target is not clear, the action mechanisms of minocycline for neuroprotection reported so far are; via; the inhibition of mitochondrial permeability-transition mediated cytochrome c release from mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression of microglial activation, involvement in some signaling pathways, metalloprotease activity inhibition. Because of the high tolerance and the excellent penetration into the brain, minocycline has been clinically tried for some neurodegenerative diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic lateral sclerosis, Hungtington's disease and Parkinson's disease. This review will briefly summarize the effects and action mechanisms of minocycline on neurodegenerative diseases.
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PMID:Minocycline and neurodegenerative diseases. 1897 95

Minocycline is neuroprotective in clinical and experimental stroke studies, due in part to its ability to inhibit poly (ADP-ribose) polymerase. Previous preclinical data have shown that interference with poly (ADP-ribose) polymerase signaling leads to sex-specific neuroprotection, reducing stroke injury only in males. In this study, we show that minocycline is ineffective at reducing ischemic damage in females after middle cerebral artery occlusion, likely due to effects on poly (ADP-ribose) polymerase signaling. Clinical trials must consider possible sex differences in the response to neuroprotective agents, if we hope to translate promising therapies to stroke patients of both sexes.
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PMID:Sex differences in minocycline-induced neuroprotection after experimental stroke. 1919 Jun 54

Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10 microM ferrous sulfate for 24h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30 microM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100 microM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models.
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PMID:Minocycline attenuates iron neurotoxicity in cortical cell cultures. 1952 48

Tetracyclines are a class of antibiotics which could play a therapeutic role in several neurological disorders. Minocycline, extensively studied in animal models, decreased the size of ischaemic and haemorrhagic infarct. In Parkinson's disease models minocycline protected the nigrostriatal pathway, and in Huntington's disease and motoneuron disease models delayed the progression of disease extending the lifespan. Finally, in human diseases such as stroke and multiple sclerosis tetracyclines seem to play some neuroprotective role. The main biological effects of tetracyclines are the inhibition of microglial activation, the attenuation of apoptosis, and the suppression of reactive oxygen species production. These mechanisms are involved in the pathogenesis of several neurodegenerative disorders. Several reports showed that minocycline reduced mitochondrial Ca(2+) uptake, stabilized mitochondrial membranes, and reduced the release into the cytoplasm of apoptotic factors. Other effects include up-regulation of mitochondrial bcl-2 (an antiapoptotic protein), direct scavenging of reactive oxygen species, and inhibition of mitogen activated protein kinases. It is still unclear which of these mechanisms plays the pivotal role in neuroprotective properties of tetracyclines. The anti-apoptotic effect of tetracyclines probably involves the mitochondrion. The major target for tetracyclines in neurodegeneration could lie within the complex network that links mitochondria, oxidative stress, poly (ADP-ribose) polymerase-1 and apoptosis. Here, we review the neuroprotective effects of tetracyclines in animal models and in human disease, and we focus on their possible mechanism(s) of action, with special regard to mitochondrial dysfunction in neurodegeneration.
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PMID:Neuroprotective effects of tetracyclines: molecular targets, animal models and human disease. 1960 19

There is only 1 US Food and Drug Administration-approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in the clinical trials conducted to date.
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PMID:Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: minocycline. 2041 Aug 69

Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.
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PMID:Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: minocycline. 2057 23


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