A5083855643- Barrier Structure and Function Studies
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Long-Term Effects of COVID-19
- Caveolin-1 and cellular processes
- Intracerebral and Subarachnoid Hemorrhage Research
- Connexins and lens biology
- Neonatal and fetal brain pathology
- Epilepsy research and treatment
- Drug Transport and Resistance Mechanisms
- Retinal Development and Disorders
- Vagus Nerve Stimulation Research
- Photoacoustic and Ultrasonic Imaging
- Retinal Diseases and Treatments
- MicroRNA in disease regulation
- Angiogenesis and VEGF in Cancer
- Redox biology and oxidative stress
- Apelin-related biomedical research
- Pharmacological Effects and Toxicity Studies
- Heme Oxygenase-1 and Carbon Monoxide
- Adenosine and Purinergic Signaling
- Congenital heart defects research
- Mosquito-borne diseases and control
- Neuroscience of respiration and sleep
Trinity College Dublin
2016-2025
Morehouse School of Medicine
2025
Science Foundation Ireland
2024
Royal College of Surgeons in Ireland
2024
22q11 Ireland
2016
Dublin City University
2014
Johns Hopkins University
1898
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and very weak nominal association tight junction protein, claudin-5, has previously been identified. Claudin-5 expressed in endothelial cells forming part blood-brain barrier (BBB). Furthermore, occurs 30% individuals 22q11 deletion syndrome (22q11DS), population who are haploinsufficient for claudin-5 gene. Here, we variant gene weakly associated...
Abstract Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function affected these conditions. Here we show that BBB evident during acute infection patients COVID cognitive impairment, commonly referred as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, COVID-associated Transcriptomic analysis of...
Major psychiatric disorders affect 25% of the population. While genetic and environmental risk factors have been identified, underlying pathophysiology conditions, such as schizophrenia, bipolar disorder major depression remains largely unknown. Here, we show that endothelial associated tight junction components are differentially regulated at blood-brain barrier (BBB) in distinct neuroanatomic regions human donor brain tissues. Previous studies shown associations between BBB disruption...
Abstract Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB remain to be elucidated. Tight junction proteins are important regulators integrity and in particular, tight protein claudin-5 most enriched brain endothelial cells regulates size-selectivity at BBB. Additionally, disruption expression has been implicated numerous disorders including schizophrenia, depression traumatic injury, yet its role not fully...
Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance [MRI] computed tomography [CT] scanning), a far greater challenge associated with subsequent management mild TBI (mTBI), especially concussion which, by definition, characterized normal CT. To investigate whether integrity blood–brain barrier (BBB) altered in high-risk population for concussions, we studied professional mixed martial arts (MMA)...
The blood–brain barrier (BBB) is highly selective and acts as the interface between central nervous system circulation. While BBB critical for maintaining brain homeostasis, it represents a formidable challenge drug delivery. Here we synthesized gold nanoparticles (AuNPs) targeting tight junction specifically demonstrated that transcranial picosecond laser stimulation of these AuNPs post intravenous injection increases permeability. permeability change can be graded by intensity, entirely...
Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over age 55 showing early signs condition. There are currently no forms therapy available for end stage dry AMD, geographic atrophy (GA). Here, we show that inner blood-retina barrier (iBRB) highly dynamic and may play a contributory role GA development. We have discovered gene CLDN5, which encodes claudin-5, tight junction protein abundantly expressed at...
Retinal degeneration is a form of neurodegenerative disease and the leading cause vision loss globally. The Toll-like receptors (TLRs) are primary components innate immune system involved in signal transduction. Here we show that TLR2 induces complement factors C3 CFB, common rate-limiting alternative pathway both retinal pigment epithelial (RPE) cells mononuclear phagocytes. Neutralization reduces opsonizing fragments outer retina protects photoreceptor neurons from oxidative stress-induced...
Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models epilepsy. In this study, we used assays serum protein tracer extravasation to determine BBB disruption occurring after...
The blood-brain barrier (BBB) is a semi-permeable microvascular barrier, composed of endothelial cells conjoined by tight junction proteins. Following pathological conditions, i.e., traumatic brain injury (TBI), BBB dysfunction occurs, leading to hyperpermeability, resulting in cerebral edema formation and elevated intracranial pressure. Recent evidence suggests that the activation pro-inflammatory signaling pathways critical dysfunction. NLRP3 inflammasome has been implicated as key...
Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition characterized by the perivascular deposition of phosphorylated τ (p-τ) protein aggregates resulting from repetitive mild brain injury (rTBI). Advances in field have revealed significance head trauma pathogenesis CTE contact sports as well military veterans. In this study we provide evidence blood-brain barrier (BBB) disruption regions intense p-τ former professional boxer diagnosed with and schizophrenia. P-τ was...
The A10 and A7r5 cell lines derived from the thoracic aorta of embryonic rat are widely used as models non-differentiated, neonatal neointimal vascular smooth muscle cells in culture. recent discovery resident multipotent stem within vessel wall has necessitated identity origin these be revisited. In this context, we examined to establish similarities differences between isolated adult aortas by determining their differentiation state, marker expression multipotency potential vitro.Vascular...
The blood-brain barrier (BBB) restricts clinically relevant accumulation of many therapeutics in the CNS. Low-dose methamphetamine (METH) induces fluid-phase transcytosis across BBB endothelial cells vitro and could be used to enhance CNS drug delivery. Here, we show that low-dose METH significant leakage rodents ex vivo vivo. Notably, leaves tight junctions intact transient via caveolar transport, which is suppressed at 4°C caveolin-1 (CAV1) knockout mice. enhances brain penetration both...
Abstract Vascular disruption has been heavily implicated in COVID-19 pathogenesis and may predispose the neurological sequelae associated with condition now known as long COVID. To date, no studies have objectively assessed blood-brain barrier (BBB) function individuals complications stemming from prior SARS-CoV-2 infection. Here, we explored neurobiological effects of infection humans acute (n = 76) those persistent COVID without impairment. Following infection, patients impairment had...
Abstract Vascular disruption has been heavily implicated in COVID-19 pathogenesis and may predispose the neurological sequelae associated with condition now known as long COVID. To date, no studies have objectively assessed blood-brain barrier (BBB) function individuals complications stemming from prior SARS-CoV-2 infection. Here, we explored neurobiological effects of infection humans acute (n = 76) those persistent COVID without impairment. Following infection, patients impairment had...
Claudin-5 is one of the most essential tight junction proteins at blood-brain barrier. A single nucleotide polymorphism rs10314 located in 3'-untranslated region claudin-5 and has been shown to be a risk factor for schizophrenia. Here, we show that pumilio RNA-binding protein, pumilio-1, responsible rs10314-mediated regulation. The RNA sequence surrounding highly homologous canonical pumilio-binding mRNA with produces 25% less protein due its inability bind pumilio-1. Pumilio-1 formed...