Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy

Yan, Ping; Zhu, Alec; Liao, Fan; Xiao, Qingli; Kraft, Andrew W.; Gonzales, Ernesto R.; Perez, Ronald A.; Greenberg, Steven M.; Holtzman, David M.; J, Lee

doi:10.1161/strokeaha.115.008582

Cited by 32 publications

(26 citation statements)

References 60 publications

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“…There are several new CypA inhibitors recently developed and investigated for use against hepatitis-C and HIV infections including CPI-431-32 [197], compound 25 [198], SCY-635 [199] and MM284 [200], which all may have a potential to stabilize the BBB in APOE4 carriers. In addition to CypA inhibitors, there are a number of identified MMP-9 inhibitors including minocycline [201], curcumin [202], SB-3CT(2) [203] and compound 18 [204]. For example, minocycline has been demonstrated to reduce hemorrhage frequency and increase endothelial tight junction and basement membrane proteins in aged 5xFAD/ APOE4 transgenic mice [201].…”

Section: Vasculoprotective Approachesmentioning

confidence: 99%

“…In addition to CypA inhibitors, there are a number of identified MMP-9 inhibitors including minocycline [201], curcumin [202], SB-3CT(2) [203] and compound 18 [204]. For example, minocycline has been demonstrated to reduce hemorrhage frequency and increase endothelial tight junction and basement membrane proteins in aged 5xFAD/ APOE4 transgenic mice [201]. Furthermore, recent studies showed that minocycline significantly reduced the infarct size, prevented tissue loss, improved perfusion, reduced BBB permeability, and increased tight junction protein levels in spontaneously hypertensive stroke-prone rats [205,206].…”

Section: Vasculoprotective Approachesmentioning

confidence: 99%

See 1 more Smart Citation

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

Nelson

Sweeney

Sagare

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

437

423

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Vascular insults can initiate a cascade of molecular events leading to neurodegeneration, cognitive impairment and dementia. Here, we review the cellular and molecular mechanisms in cerebral blood vessels and the pathophysiological events leading to cerebral blood flow dysregulation and disruption of the neurovascular unit and the blood-brain barrier, which all may contribute to the onset and progression of dementia and Alzheimer’s disease (AD). Particularly, we examine the link between neurovascular dysfunction and neurodegeneration including the effects of AD genetic risk factors on cerebrovascular functions and clearance of Alzheimer’s amyloid-β peptide toxin, and the impact of vascular risk factors, environment and lifestyle on cerebral blood vessels, which in turn may affect synaptic, neuronal and cognitive functions. Finally, we examine potential experimental treatments for dementia and AD based on the neurovascular model, and discuss some critical questions to be addressed by future studies.

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Section: Vasculoprotective Approachesmentioning

confidence: 99%

Section: Vasculoprotective Approachesmentioning

confidence: 99%

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

Nelson

Sweeney

Sagare

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

437

423

View full text Add to dashboard Cite

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“…The minocycline hugely modified the MMP and inflammatory pathways in a positive way and connecting to that, higher levels of microvascular tight junction and basal lamina proteins were found, proving its BBB protective effect, which could be utilized in ischemic stroke treatment, parallel to rtPA administration [157]. Furthermore, minocyclin was tested on spontaneous hypertensive rats as well.…”

Section: Minocyclinmentioning

confidence: 88%

“…Caspase-1, caspase-3, cyclo-oxygenase-2, inducible nitric oxide synthase, p38 mitogenactivated protein kinase, gelatinase, MMP-9 are supposed to participate in the molecular mechanism of minocycline [157,160].…”

Section: Minocyclinmentioning

confidence: 99%

Hemorrhagic transformation of ischemic stroke

J¹,

Hortobágyi²

2017

Vascul Dis Ther

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The better understanding of the diverse mechanisms leading to the hemorrhagic transformation of an ischemic stroke is the crucial point in the prevention of this altogether common phenomenon. The different individual risk factors include the anatomical variability of collateral blood supply, age, genetics, body weight, etiology of the occlusion, side of the occluded vessel, renal status, stroke severity, history of high serum glucose or hypertension and hypertension or hyperglycemia at the onset of the stroke, ferritin level, INR, antiplatelet usage or the platelet count etc. All these might contribute to the process of hemorrhagic transformation. These risk factors have been identified by retrospective epidemiological studies and are useful to identify patients who are at high risk for hemorrhagic conversion and help the decision between conservative, thrombolytic or more advanced treatments such as thrombectomy. The modulations of potential molecular targets participating in the process seem to be promising in animal models, but human trials are lacking the breakthrough success so far, both in extending the time frame of the thrombolysis and in replacing the recombinant tissue plasminogen activator (rtPA) as thrombolytic agent.So far, the careful preselection of patients eligible for thrombolytic therapy is the best way to prevent hemorrhagic transformation. The intensive research in the field revealing small but important molecular details are continuously contributing to the better understanding of hemorrhagic transformation with the intention of finding new agents that co-administrated to the rtPA or completely replacing that could decrease the risk of secondary bleeding.The aim of this review is to give comprehensive insight into the process of hemorrhagic transformation of ischemic stroke, starting with basic overview of the penumbra concept and the collateral supply followed by discussion of the recanalisation-reperfusion-hemorrhagic transformation process after vessel occlusion also highlighting the importance of timing and ratio of recanalisation spontaneously and in case of thrombolytic agent administration. We overview the risk factors of hemorrhagic transformation, which may be helpful to physicians to identify high risk patients before rtPA administration. The last part of the work is dealing with future therapeutic possibilities based on the so far revealed molecular mechanisms of hemorrhagic transformation. With the aim to assess the rate and influencing factors on the recanalisation and reperfusion rate 381 patients with large-vessel occlusion was investigated. The patient group involved ones treated with rtPA or treated conservatively. Partial or complete recanalisation was achieved in 121 out of 210 (58%) patients after intravenous rtPA administration. The recanalisation success was more likely if the patient had atrial fibrillation [4] -maybe because cardioembolic clots consists more fibrin and are more likely to reopen by plasmin proteolysis than thrombosis of an atherosclerotic plaq...

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“…Son dönemde fareler üzerinde yapılan bir çalışmada SAA'da minosiklinin, gliyozisi ve enflamatuvar gen ekspresyonunu azalttığı gösterilmiştir. Ayrıca, minosiklin ile tedavi edilen farelerde mikrovasküler sıkı bağlantıların "tight junction" ve bazal lamina proteinlerinin arttığı saptanmış olmakla birlikte, SAA ilişkili beyin kanamalarını önlemedeki etkinliğinin klinik çalışmalarla desteklenmesi gereklidir [47] .…”

Section: Nöroprotektif Etkiunclassified

Non Antimicrobial Effects of Antibacterial Agents

Demiraslan¹,

Uysal²

2018

mjima

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Aside from their antibacterial activity, antimicrobial agents have also some beneficial effects due to their chemical structures. These effects include anti-inflammatory, immunomodulatory, anti-cancer, anti-angiogenic, neuroprotective, cardioprotective, augmented gastrointestinal motility, and binding toxins. This paper does not comprise non-antimicrobial effects of all antibiotics due to the fact that the issue is very extended. We reviewed use of penicillins in mushroom poisoning and their promising inhibitor effect on proliferation of cervical carcinoma and leukemia cells. We summarized neuroprotective effect of ceftriaxone and its inhibitory potential on proliferation of lung cancer cells. Tetracyclines are agents that have been focused on and investigated for a long time, and demeclocycline that belongs to this group is used for inappropriate antidiuretic hormone secretion. Moreover, low-dose doxycycline that is also a tetracycline, has been approved for the treatment of periodontitis, and inhibition of matrix metalloproteinase enzyme is the responsible mechanism for its anti-inflammatory action. Matrix metalloproteinase inhibition also provides a decrease in tumor angiogenesis and metastasis. Minocycline, another tetracycline, reduces the synthesis of beta-amyloid which plays a key role in Alzheimer's disease and other neurodegenerative diseases, and it also inhibits glial inducible nitric oxide (NO) synthase and NOmediated neurotoxicity. Erythromycin that is a macrolide antibiotic is used as a gastrointestinal motility augmenter; azithromycin gives an early improvement in patients with cystic fibrosis due to its anti-inflammatory effect. It has been shown that clarithromycin decreases the metastatic AbstractAntimikrobiyal ajanlar kimyasal yapılarından dolayı bakterilere karşı aktiviteleri dışında bazı yararlı etkilere de sahiptirler. Bunlar arasında antienflamatuvar, immünomodülatör, anti-kanser, anti-anjiyogenik, nöroprotektif, kardiyoprotektif, gastrointestinal hareket artırıcı ve toksin bağlayıcı etkiler sayılabilir. Bu yazıda, konu çok geniş olduğundan dolayı sınırlı sayıda antibiyotiğin antimikrobiyal dışı etkileri ele alınmıştır. Penisilinlerin serviks ve lösemik kanser hücrelerinin çoğalmasını durdurma konusunda ümit vaat edici etkisi ve mantar zehirlenmesi tedavisinde kullanımı; seftriaksonun akciğer kanseri hücreleri üzerindeki çoğalmayı önleyici potansiyeli ve nöroprotektif etkisi derlenmiştir. Tetrasiklinler uzun süredir üzerinde durulan ve araştırılan ajanlardır ve bu gruptaki demeklosiklin, uygunsuz antidiüretik hormon salınımında kullanılmaktadır. Ayrıca tetrasiklinlerden doksisiklin düşük dozda periodontit tedavisi için onay almıştır ve anti-enflamatuvar etkiden sorumlu mekanizma matriks metalloproteinaz (MMP) enzimi inhibisyonudur. Ayrıca MMP inhibisyonu metastazda ve tümör anjiyogenezinde azaltma da sağlayabilmektedir. Diğer bir tetrasiklin olan minosiklin ise Alzheimer ve diğer nörodejeneratif hastalıklarda kilit rolü olan beta-amilod sentezini azaltmakta ve ayrıca gliyal indüklenebilir ...

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Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy

Cited by 32 publications

References 60 publications

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

Hemorrhagic transformation of ischemic stroke

Non Antimicrobial Effects of Antibacterial Agents

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