Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke

Machado, Sandro Lemos; Kozák, Anna; Ergul, Adviye; Hess, David C.; Borlongan, Cesario V.; Fagan, Susan C.

doi:10.1186/1471-2202-7-56

Cited by 170 publications

(79 citation statements)

References 38 publications

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“…In addition, excessive ROS induces DNA damage, which activates P53 and increases P53 protein expression [17]. In ischemic injury, minocycline has been demonstrated to reduce infarct size and neurological deficits in animal models of focal/global cerebral ischemia [45][46][47]. The potential mechanism underlying these neuroprotective effects of minocycline may include the following: inhibitory effect on cell apoptosis via the reduction expression of caspase-3 and poly polymerase-1, inhibitory effect on expression and activity of MMPs, and inhibitory effect on activation of microglia.…”

Section: Discussionmentioning

confidence: 99%

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage

Chen

et al. 2015

Mol Neurobiol

116

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Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

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Section: Discussionmentioning

confidence: 99%

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage

Chen

et al. 2015

Mol Neurobiol

116

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“…This effect has been studied in various models, and the inhibitory and protective effects have been reported in many cell types, animal models, and clinical trials. Based on in vitro cell culture measurements, myocardial ischemia-reperfusion rat models, and studies on patients with atherosclerotic lesions, vascular aneurysms, myocardial infarction, cerebrovascular abnormalities, periodontitis, and metabolic bone diseases, the tetracyclines (tetracycline, doxycycline, minocycline, and chemically modified tetracyclines) have shown different potencies in inhibiting various involving MMPs (10)(11)(12)(13)(14)(15)(16). In these studies, the obtained IC50 values ranged from 5 to 500 µM among the different MMPs.…”

Section: Introductionmentioning

confidence: 99%

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Modheji

Olapour

Khodayar

et al. 2016

Jundishapur J Nat Pharm Prod

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Background: Tetracyclines are antimicrobial agents that possess anti-inflammatory and matrix metalloproteinase (MMP) inhibitory effects. Tetracycline, doxycycline, and minocycline have shown different potencies in inhibiting various MMPs. MMPs are a conserved family of zinc-dependent endopeptidases, which are involved in various physiologic and pathologic conditions. MMP-9 is among the most important proteases involved in the development of cardiovascular disease, cancer, and inflammatory disease Objectives: Considering the central role of MMP-9 in the above-mentioned diseases and the variable inhibitory potentials of routine tetracyclines, including tetracycline, doxycycline, and minocycline, this study measured the inhibitory effect of these routine tetracycline agents on MMP-9 activity obtained from U-937 cell cultures using the zymography method. Materials and Methods: An MMP-9-rich culture medium of U-937 cells was used as the source of the enzyme. Serial dilutions of 5, 20,

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“…It effectively crosses the blood-brain barrier, targets microglia by inhibiting the production of proinflammatory cytokines and NO and reduces their migration to injured neurons [134]. An inhibition of the MMP-9 pathway was described for both minocycline and doxycycline [135,136]. Minocycline has been shown to be neuroprotective in several adult animal models of neurological disorders [137,138,139,140,141,142,143,144].…”

Section: The Bad Guys? Microglia and Neurodegenerationmentioning

confidence: 99%

The Yin and Yang of Microglia

2011

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Microglia, the resident immune cells of the mammalian central nervous system (CNS), play a pivotal role in both physiological and pathological conditions such as the restoration of CNS integrity and the progression of neurodegenerative disorders. Extensive data have been published that describe neuroinflammation by microglial activation to have detrimental consequences on the developing and mature brain. On the other hand, a properly directed and limited inflammatory response is known to be a natural healing process after an insult in several other tissues. Thus, it is not surprising that research results illustrating benefits of neuroinflammation have been emerging over the past decade. Inflammation-mediated benefits for CNS outcomes include mechanisms such as neuroprotection, mobilization of neural precursors for repair, remyelination and axonal regeneration. Here, we review data that highlight the dual aspects of microglia with a focus on the developing brain, i.e. as aggressors potentiating damage and as helpers in the recovery process following CNS damage.

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Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke

Cited by 170 publications

References 38 publications

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage

Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

The Yin and Yang of Microglia

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