ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2014
PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced in MMP-9-deficient mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Mitochondrial DNA damage in HIV infection: a mechanistic driver of immunometabolic dysfunction and chronic inflammation.Frontiers in immunology · 2025Review
- Matrix Metalloproteinase-9 Signaling Regulates Colon Barrier Integrity in Models of HIV Infection.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Fentanyl dysregulates neuroinflammation and disrupts blood-brain barrier integrity in HIV-1 Tat transgenic mice.Journal of neurovirology · 2024Article
- Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Review
- PPAR Gamma and Viral Infections of the Brain.International journal of molecular sciences · 2021Review
- Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders.Fluids and barriers of the CNS · 2020Review
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
- Effects of angiotensin-II on brain endothelial cell permeability via PPARalpha regulation of para- and trans-cellular pathways.Brain research · 2019Review
- HIV and Alzheimer's disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein.Journal of neurovirology · 2019Review
- Peroxisome Proliferator-Activated Receptor-gamma agonists exhibit anti-inflammatory and antiviral effects in an EcoHIV mouse model.Scientific reports · 2019Article
- All-Trans Retinoic Acid Ameliorates the Early Experimental Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting the Loss of the Blood-Brain Barrier via the JNK/P38MAPK Signaling Pathway.Neurochemical research · 2018Article
- Generation of Hutat2:Fc Knockin Primary Human Monocytes Using CRISPR/Cas9.Molecular therapy. Nucleic acids · 2018Article
- Peroxisome proliferator-activated receptor-gamma: potential molecular therapeutic target for HIV-1-associated brain inflammation.Journal of neuroinflammation · 2017Article
- Tat is a multifunctional viral protein that modulates cellular gene expression and functions.Oncotarget · 2017Review
- Multifaceted Mechanisms of WY-14643 to Stabilize the Blood-Brain Barrier in a Model of Traumatic Brain Injury.Frontiers in molecular neuroscience · 2017Article
- HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway.Oxidative medicine and cellular longevity · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
The strategies to protect against the disrupted blood-brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPARα agonist) or rosiglitazone (PPARγ agonist). In contrast, exposure to GW9662 (PPARγ antagonist) exacerbated Tat-induced disruption of the BBB integrity. Increased BBB permeability was associated with decreased tight junction (TJ) protein expression and activation of ERK1/2 and Akt in brain microvessels; these effects were attenuated by cotreatment with fenofibrate but not with rosiglitazone. Importantly, both PPAR agonists also protected against Tat-induced astrogliosis and neuronal loss. Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.