A5006130007- Traumatic Brain Injury and Neurovascular Disturbances
- Neonatal and fetal brain pathology
- Cardiac Arrest and Resuscitation
- Eicosanoids and Hypertension Pharmacology
- Hemoglobin structure and function
- Neuroscience of respiration and sleep
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Heme Oxygenase-1 and Carbon Monoxide
- Anesthesia and Neurotoxicity Research
- Thermal Regulation in Medicine
- Acute Ischemic Stroke Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced MRI Techniques and Applications
- Metabolism and Genetic Disorders
- Cardiac Ischemia and Reperfusion
- Optical Imaging and Spectroscopy Techniques
- Respiratory Support and Mechanisms
- High Altitude and Hypoxia
- Mechanical Circulatory Support Devices
- Mitochondrial Function and Pathology
- Pregnancy and preeclampsia studies
- Neonatal Respiratory Health Research
- Neurological Disease Mechanisms and Treatments
- Receptor Mechanisms and Signaling
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Children's Center
2019-2021
Bloomberg (United States)
2019-2021
Eckert & Ziegler (United States)
2013-2019
National Institutes of Health
1996-2016
University of Southern Denmark
2015
University of Baltimore
2015
Johns Hopkins Hospital
1982-2014
Center for Translational Molecular Medicine
2010
Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various models cellular injury. Here, we identify (PAR) polymer, product PARP-1 activity, as previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation by glycohydrolase (PARG) or phosphodiesterase 1 prevents polymer-induced death. PARP-1-dependent, NMDA excitotoxicity cortical neurons reduced neutralizing antibodies overexpression PARG....
Intracerebral hemorrhage (ICH) causes high mortality and morbidity, but our knowledge of post-ICH neuronal death related mechanisms is limited. In this study, we first demonstrated that ferroptosis, a newly identified form cell death, occurs in the collagenase-induced ICH model mice. We found administration ferrostatin-1, specific inhibitor prevented reduced iron deposition induced by hemoglobin organotypic hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after exhibited...
Mice, homozygous for prion protein (PrP) gene ablation (Prn-p0/0), develop normally and remain well > 500 days after inoculation with murine scrapie prions. In contrast, wild-type mice developed < 165 most Prn-p0/+ mice, heterozygous disruption of the PrP gene, exhibited signs central nervous system dysfunction between 400 465 inoculation. situ immunoblots showed widespread deposition (PrPSc) in brains both Prn-p+/+ while neither cellular (PrPC) nor PrPSc was detected Prn-p0/0 mice. contrast...
The goals of this study were to quantify the effects epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) CPR with simultaneous chest compression-ventilation test hypothesis that would improve by preventing collapse intrathoracic arteries vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral measured radiolabeled microsphere technique, which we have previously validated CPR. We studied effect established...
Background and Purpose— Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) critically ill patients. The ability to detect loss autoregulatory vasoreactivity spontaneous fluctuations CPP was tested with new time-domain that used near-infrared spectroscopic measurements tissue oxyhemoglobin saturation an infant animal model. Methods— Piglets were made progressively hypotensive over 4 5 hours by inflation...
The neonatal striatum degenerates after hypoxia-ischemia (H-I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration H-I. Newborn piglets were subjected 30 minutes hypoxia (arterial O2 saturation, 30%) then 7 airway occlusion (O2 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% putaminal neurons injured, without differing significantly...
The mechanism of brain swelling during hyperammonemia is not understood, but glutamine accumulation consistently observed. We tested the hypothesis that associated with a consequence osmotic effect intracellular in brain. Increases plasma ammonium levels from 31 +/- 3 to 601 38 mumol/l (+/- SE) were produced by 6 h infusion acetate anesthetized rats. Hyperammonemia resulted increased water content accompanied more than tripling concentration compared control rats receiving sodium (5.6 0.4...
Clinical application of continuous autoregulation monitoring would benefit from a comparison curves generated by online with standard in animal models. We characterized the accuracy 3 monitors piglet model hypotension.Piglets 5 to10 days old intracranial pressure (ICP) at naïve or elevated (20 mm Hg) levels had gradual arterial hypotension induced balloon catheter inferior vena cava. Elevated ICP was maintained infusion artificial cerebrospinal fluid. Three indices were simultaneously and...
A bstract : Polyphenolic compounds, such as resveratrol, are naturally present at high concentration in grape skin, seeds, and red wine. Resveratrol is cis trans isoforms the major isomer biologically active one. Epidemiologic studies have revealed a reduced incidence of cardiovascular risk associated with consumers wine; this has been popularized French paradox . shown to significant antioxidant properties variety vitro vivo models. It can reduce ischemic damage heart ischemia reperfusion...
Background and Purpose— The pressure reactivity index (PRx) describes cerebral vessel by correlation of slow waves intracranial (ICP) arterial blood pressure. In theory, changes in the relative total hemoglobin (rTHb) measured near-infrared spectroscopy are caused same volume that cause ICP. Our objective was to develop a new vascular reactivity, (HVx), which is low-frequency rTHb with spectroscopy. Methods— Gradual hypotension induced piglets while cortical laser-Doppler flux monitored. ICP...
Recent studies have demonstrated that for the same chest compression force during mechanical cardiopulmonary resuscitation (CPR), carotid artery-to-jugular vein pressure gradient and blood flow are increased when phasic rise of intrathoracic is enhanced by abdominal binding simultaneous ventilation at high airway with each (SCV). The objective present study was to assess whether cerebral also enhanced, since it known fluctuations in transmitted intracranial space affect (ICP). In two series...
Cerebral blood flow (CBF) falls as hematocrit (Hct) rises. Investigators have differed on the relative importance of increases in arterial O2 content (CaO2) and red cell concentration mediating fall. Our experimental protocol attempted to determine independent effects these two variables. In 13 unanesthetized lambs (less than 7 days old) we measured sagittal sinus gases, contents, CBF (microsphere technique) at oxyhemoglobin Hcts approximately 20 40% after an isovolemic exchange transfusion...
Significance Non–image-forming opsins such as Opn4 regulate important physiological functions circadian photo-entrainment and affect. The recent discovery that melanopsin (Opn4) outside the central nervous system prompted us to explore a potential role for this receptor in blood vessel regulation. We hypothesized Opn4-mediated signaling might explain phenomenon of photorelaxation, which mechanism has remained elusive. report presence vessels demonstrate it mediates wavelength-specific,...
Background End‐tidal carbon dioxide ( ETCO 2 ) correlates with systemic blood flow and resuscitation rate during cardiopulmonary CPR may potentially direct chest compression performance. We compared ‐directed compressions optimized to pediatric basic life support guidelines in an infant swine model determine the effect on of return spontaneous circulation ROSC ). Methods Results Forty 2‐kg piglets underwent general anesthesia, tracheostomy, placement vascular catheters, ventricular...