ArticleJournal of molecular neuroscience : MN2012
Doxycycline-mediated protective effect against focal cerebral ischemia-reperfusion injury through the modulation of tight junctions and PKCδ signaling in rats.
Article in Journal of molecular neuroscience : MN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Anti-inflammatory and neuroprotective effect of bryodulcosigenin against cerebral ischemia/reperfusion injury via modulation of inflammatory signaling pathways.Inflammopharmacology · 2026Article
- Association of MMP-9 and TIMP-1 concentration with neurological outcome after cardiac arrest and resuscitation - a substudy of the COMACARE trial.Resuscitation plus · 2026Article
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.Journal of clinical medicine · 2025Review
- The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Post-stroke Impairment of the Blood-Brain Barrier and Perifocal Vasogenic Edema Is Alleviated by Endovascular Mesenchymal Stem Cell Administration: Modulation of the PKCδ/MMP9/AQP4-Mediated Pathway.Molecular neurobiology · 2022Article
- Doxycycline prevents blood-brain barrier dysfunction and microvascular hyperpermeability after traumatic brain injury.Scientific reports · 2022Article
- Effects of 9-t-butyl doxycycline on the innate immune response to CNS ischemia-reperfusion injury.Experimental and molecular pathology · 2021Article
- Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington's Disease.Molecular neurobiology · 2020Article
- Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization.Theranostics · 2020Article
- High serum levels of tissue inhibitor of matrix metalloproteinase-1 during the first week of a malignant middle cerebral artery infarction in non-surviving patients.BMC neurology · 2019Observational
- Antibiotic Class and Outcome in Post-stroke Infections: An Individual Participant Data Pooled Analysis of VISTA-Acute.Frontiers in neurology · 2019Article
- Doxycycline inhibits experimental cerebral malaria by reducing inflammatory immune reactions and tissue-degrading mediators.PloS one · 2018Article
- In Situ Pluripotency Factor Expression Promotes Functional Recovery From Cerebral Ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction.BMC neurology · 2015Article
- Is there new hope for therapeutic matrix metalloproteinase inhibition?Nature reviews. Drug discovery · 2014Review
- Neuroprotection in stroke: past, present, and future.ISRN neurology · 2014Review
- Electroacupuncture treatment improves neurological function associated with regulation of tight junction proteins in rats with cerebral ischemia reperfusion injury.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.BMC complementary and alternative medicine · 2013Article
- Does inhibiting Sur1 complement rt-PA in cerebral ischemia?Annals of the New York Academy of Sciences · 2012Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The strategy for the development of effective and safe neuroprotective agents has great potential to reduce cerebral ischemia-reperfusion injury and improve the functional outcome in stroke patients. Recently, doxycycline, a tetracycline antibiotic, has been shown to have neuroprotective efficiency in reduction of a variety of ischemia-reperfusion injuries as well as ischemic brain damage. We used the rat models of middle cerebral artery occlusion (MCAO) and reperfusion to investigate the effects of treatments with doxycycline against the blood-brain barrier (BBB) leakage at 3, 12, 72, and 120 h of reperfusion. Male Sprague-Dawley rats were subjected to MCAO for 2 h followed by reperfusion for 3, 12, 72, and 120 h and received either doxycycline (45 mg/kg) or saline. The results showed that the treatment of doxycycline significantly reduced the BBB leakage and cerebral infarct volume, which were proved by Evans blue assay and TTC staining. Real-time PCR, immunohistochemistry, and western blot assay verified that the administration of doxycycline significantly up-regulated the expression of tight junction claudin-5, occludin, and ZO-1 from 3 to 120 h after reperfusion. The results of real-time PCR, western blot, and gelatin zymography analyses revealed that the gene and protein expression and activities of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 were significantly elevated in a different time-dependent manner after ischemia-reperfusion but significantly inhibited by doxycycline treatment. Moreover, doxycycline could also significantly down-regulate the expression of PKCδ mRNA and protein after ischemia-reperfusion. These results suggested that the protective effects of doxycycline against BBB damage induced by reperfusion might be related to the up-regulation of tight junction proteins and inhibition of MMP-2, MMP-9, and PKCδ.
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