A5002141375- Vascular Malformations Diagnosis and Treatment
- Intracerebral and Subarachnoid Hemorrhage Research
- Intracranial Aneurysms: Treatment and Complications
- Traumatic Brain Injury and Neurovascular Disturbances
- Neurosurgical Procedures and Complications
- Acute Ischemic Stroke Management
- Cerebrospinal fluid and hydrocephalus
- MRI in cancer diagnosis
- S100 Proteins and Annexins
- Carcinogens and Genotoxicity Assessment
- Glioma Diagnosis and Treatment
- Brain Tumor Detection and Classification
- Nerve injury and regeneration
- Retinal and Macular Surgery
- Metabolomics and Mass Spectrometry Studies
- Advanced MRI Techniques and Applications
- Signaling Pathways in Disease
- Bone and Joint Diseases
- Testicular diseases and treatments
- Advanced Neuroimaging Techniques and Applications
- Pesticide Exposure and Toxicity
- Vascular Malformations and Hemangiomas
- Neural and Behavioral Psychology Studies
- Extracellular vesicles in disease
- Menopause: Health Impacts and Treatments
University of Chicago
2016-2025
Neurological Surgery
2018-2025
The University of Texas MD Anderson Cancer Center
2024
Stanford University
2019
University of Cincinnati
2019
University of Cincinnati Medical Center
2019
Johns Hopkins University
2018-2019
University of Kansas
2019
Newcastle University
2019
The University of Texas at San Antonio
2019
Increases in mean lesional iron content by quantitative susceptibility mapping (QSM) ≥6% and/or vascular permeability dynamic contrast enhanced perfusion (DCEQP) ≥40% on MRI have been associated with new symptomatic hemorrhage (SH) cerebral cavernous malformations (CCMs). It is not known if plasma biomarkers can reflect these changes within the lesion proper. This cohort study enrolled 46 CCM patients SH prior year. Plasma samples, QSM and DCEQP were simultaneously acquired at beginning end...
Abstract BACKGROUND Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome supratentorial brain hemorrhage, morbid disabling type stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary (modified Rankin scale score 0 3 at 1 yr). OBJECTIVE To assess surgical performance its impact...
Background and Purpose— We sought to compare the effect of chronic treatment with commonly tolerated doses Fasudil, a specific RhoA kinase (ROCK) inhibitor, simvastatin (with pleiotropic effects including ROCK inhibition) on cerebral cavernous malformation (CCM) genesis maturation in 2 models that recapitulate human disease. Methods— Two heterozygous murine models, Ccm1 +/− Msh2 − /− Ccm2 Trp53 −/− , were treated from weaning 4 5 months age Fasudil (100 mg/kg per day), (40 day) or placebo....
KRIT1 mutations are the most common cause of cerebral cavernous malformation (CCM). Acute Krit1 gene inactivation in mouse brain microvascular endothelial cells (BMECs) changes expression multiple genes involved vascular development. These include suppression Thbs1, which encodes thrombospondin1 (TSP1) and has been ascribed to KLF2- KLF4-mediated repression Thbs1. In vitro reconstitution TSP1 with either full-length or 3TSR, an anti-angiogenic fragment, suppresses heightened growth factor...
Abstract BACKGROUND More than a million Americans harbor cerebral cavernous angioma (CA), and those who suffer prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development through inhibiting RhoA kinase (ROCK), suggesting it may confer therapeutic benefit. OBJECTIVE To evaluate whether produces difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM)...
Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset earlier and more severe individuals with mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation lipopolysaccharide derived the gut microbiome. These findings suggest gut-brain disease axis but fail to define it explain...
Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role CCM pathogenesis serving major source VEGF during lesion formation. An increase astrocyte synthesis is driven nitric oxide (NO) generated consequence KLF2- KLF4-dependent elevation eNOS...
Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for CCM1, CCM2, or CCM3 gene. Loss corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and mouse brains vivo. A prospective case-controlled observational study investigated whether human subjects show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, comparison cases without disease, lesional brain...
The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers prior disease severity.We hypothesize that a panel 24 candidate biomarkers, reported role in the physiopathology malformations, may predict subsequent clinically relevant activity.Plasma were assessed nonfasting peripheral venous blood collected from consecutive malformation subjects followed for 1 year after initial...
Abstract Clinical data have been equivocal and controversial as to the benefits brain cognition of hormone therapy (HT) in postmenopausal women. Recent reevaluation role estrogens proposed that HT may effectively prevent deleterious effects aging on cognition, reduces risks dementia, including Alzheimer’s disease, if initiated early at beginning menopause. Yet, little is known about activation related cognitive control, ability make flexible decisions relation internal goals. Here, we used...
Abstract BACKGROUND Minimally invasive thrombolytic evacuation of intracerebral hematoma is being investigated in the ongoing phase III clinical trial Invasive Surgery plus recombinant Tissue plasminogen activator for Intracerebral hemorrhage Evacuation (MISTIE III). OBJECTIVE To assess accuracy catheter placement and efficacy relation to surgical approach surgeon experience. METHODS We performed a midpoint interim assessment 123 cases that underwent procedure. Accuracy was prospectively...
OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior CCM lesions with longitudinal changes in biomarkers dynamic contrast-enhanced quantitative (DCEQP) susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients CCMs underwent 2 or more and/or studies conjunction baseline follow-up imaging surveillance during a mean 12.05 months (range 2.4-31.27...
Background and Purpose- Previously, murine models Krit1 +/- Msh2 -/- Ccm2 Trp53 showed a reduction or no effect on cerebral cavernous malformation (CCM) burden favorable effects lesional hemorrhage by the robust Rock (Rho-associated protein kinase) inhibitor fasudil simvastatin (a weak pleiotropic of Rock). Herein, we concurrently investigated treatment more aggressive Pdcd10/Ccm3 model with fasudil, simvastatin, higher dose atorvastatin to determined effectiveness inhibition. Methods- The...
The purpose of this study was to determine important genes, functions, and networks contributing the pathobiology cerebral cavernous malformation (CCM) from transcriptomic analyses across 3 species 2 disease genotypes. Sequencing RNA laser microdissected neurovascular units 5 human surgically resected CCM lesions, mouse brain microvascular endothelial cells, Caenorhabditis elegans with induced Ccm gene loss, their respective controls provided differentially expressed genes (DEGs). DEGs C....
The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome craniotomy (open surgery) or timing from ictus to intervention influences either procedure.To compare volume relation outcomes MISTIE STICH (Surgical Trial Intracerebral Hemorrhage) trials.Postoperative scans were performed II, but not I; therefore, surgical cases...
BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities patients, suggests environmental, genetic, or biological factors act as disease modifiers. Still, underlying mechanisms are not entirely understood. Here, we report mild hypoxia accelerates CCM by promoting angiogenesis, neuroinflammation, vascular brains mouse models. METHODS: We used genetic studies, RNA sequencing,...