A5045364135- Neuroscience and Neuropharmacology Research
- Neonatal and fetal brain pathology
- Anesthesia and Neurotoxicity Research
- Neonatal Respiratory Health Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Arrest and Resuscitation
- Ion channel regulation and function
- Trace Elements in Health
- Medicinal Plants and Neuroprotection
- Sleep and Wakefulness Research
- Cardiac electrophysiology and arrhythmias
- Biochemical effects in animals
- Neuroscience of respiration and sleep
- Infant Development and Preterm Care
- Neurogenesis and neuroplasticity mechanisms
- Anesthesia and Sedative Agents
- Nerve injury and regeneration
- Sepsis Diagnosis and Treatment
- Ion Channels and Receptors
- Thermal Regulation in Medicine
- Intensive Care Unit Cognitive Disorders
- Neural dynamics and brain function
- Nicotinic Acetylcholine Receptors Study
- Respiratory Support and Mechanisms
University of Colorado Anschutz Medical Campus
2015-2025
University of Colorado Denver
2014-2024
Children's Hospital Colorado
2017-2024
University Hospital of Bern
2023
University of New Mexico
2004-2010
Harbor–UCLA Medical Center
2004
Office of Infectious Diseases
2004
Cardiovascular Research Center
2004
St. John's School
2004
UCLA Medical Center
2004
Septic patients frequently develop cognitive impairment that persists beyond hospital discharge. The impact of sepsis on electrophysiological and molecular determinants learning is underexplored. We observed mice survived or endotoxemia experienced loss hippocampal long-term potentiation (LTP), a brain-derived neurotrophic factor-mediated (BDNF-mediated) process responsible for spatial memory formation. Memory occurred despite preserved BDNF content could be reversed by stimulation...
Spreading depression (SD) is wave of profound depolarization that propagates throughout brain tissue and can contribute to the spread injury after stroke or traumatic insults. The contribution Ca(2+) influx SD differs depending on stimulus, we show here Zn(2+) play a critical complementary role in murine hippocampal slices. In initial studies, used Na(+)/K(+) ATPase inhibitor ouabain found conditions which was always prevented by L-type channel blockers; however, not responsible for effects....
Highlights•CaMKII T286A mutation dramatically reduces neuronal injury after cardiac arrest•CaMKII inhibition is neuroprotective when administered protects in combination with therapeutic hypothermia•Very low tatCN19o doses lead to anatomical and functional neuroprotectionSummaryThe Ca2+/calmodulin-dependent protein kinase II (CaMKII) a major mediator of physiological glutamate signaling, but its role pathological signaling (excitotoxicity) remains less clear, indications for both neuro-toxic...
<b><i>Importance:</i></b> The novel coronavirus 2019 (SARS-CoV-2) has been well described in adults. Further, the impact on older children and during perinatal time is becoming better studied. As community spread increases, it important to recognize that neonates are vulnerable as well. community-acquired SARS-CoV-2 neonatal period unclear, this population unique immunity considerations. <b><i>Objective:</i></b> To report a case series of...
Abstract Cardiac arrest-induced global cerebral ischemia (GCI) in childhood often results learning and memory deficits. We previously demonstrated a murine cardiac arrest cardiopulmonary resuscitation (CA/CPR) mouse model that cellular mechanism of memory, long-term potentiation (LTP), is acutely impaired the hippocampus juvenile males, correlating with deficits tasks. However, little known regarding plasticity impairments females. performed CA/CPR (P21-25) female mice used slice...
Myelin, the insulating sheath around axons, supports axon function. An important question is impact of mild myelin disruption. In absence protein proteolipid (PLP1), generated but with age, axonal function/maintenance disrupted. Axon disruption occurs in Plp1-null mice as early 2 months cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase oligodendrocyte density olfactory bulb and rostral corpus callosum that increased during...
The current study focuses on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. In light of recent studies demonstrating delayed GABA antagonists motor function, we utilized electrophysiology, biochemistry and neurobehavioral methods investigate role α5 GABAA receptors hippocampal plasticity functional recovery following ischemic stroke. Male C57Bl/6 mice were exposed 45 min transient middle cerebral artery occlusion...
Key points Pharmacological, molecular and genetic data indicate a prominent role of low‐voltage‐activated T‐type calcium channels (T‐channels) in the firing activity both pyramidal inhibitory interneurons subiculum. Pharmacological inhibition T‐channels switched burst with lower depolarizing stimuli to regular spiking, fully abolished hyperpolarization‐induced firing. Our studies showed that Ca V 3.1 is most abundantly expressed isoform rat Consistent this finding, regular‐spiking patterns...
Spreading depression (SD) involves coordinated depolarizations of neurons and glia that propagate through the brain tissue. Repetitive SD-like events are common following human ischemic strokes, believed to contribute enlargement infarct volume. Accumulation Zn 2+ is also implicated in neuronal injury. Synaptic glutamate release contributes SD propagation, because costored with some synaptic vesicles, we examined whether released by may therefore provide a significant source postischemic...
Abstract Multiple Ca 2+ entry routes have been implicated in excitotoxic loading neurons and reverse‐operation of sodium–calcium exchangers (NCX) has shown to contribute under conditions where intracellular Na + levels are enhanced. We investigated effects KB‐R7943, an inhibitor NCX activity, on elevations single CA1 acute hippocampal slices. KB‐R7943 had no significant effect input resistance, action potential waveform, or frequency adaptation, but reduced L‐type somata. Nimodipine was...
Ischemic stroke is a leading cause of death worldwide and clinical data suggest that children may recover from better than adults; however, supporting experimental are lacking. We used our novel mouse model juvenile ischemic (MCAO) to characterize age-specific cognitive dysfunction following ischemia. Juvenile adult mice subjected 45-min MCAO, extracellular field recordings CA1 neurons were performed assess hippocampal synaptic plasticity changes after contextual fear conditioning was...
Exposure to sedative/hypnotic and anesthetic drugs, such as ketamine, during the critical period of synaptogenesis causes profound neurotoxicity in developing rodent primate brains is associated with poor cognitive outcomes later life. The subiculum especially vulnerable acute after neonatal exposure drugs. acts a relay center between hippocampal complex various cortical subcortical brain regions also an independent generator gamma oscillations. Gamma oscillations are vital neuronal...
Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on evolution simulated IE in presence and absence vancomycin or nafcillin. Staphylococcus aureus strains differing intrinsic susceptibility PMPs antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin susceptible), ISP479R (tPMP-1 resistant; GISA-NJ...
Diazepam was administered intravenously in doses of 10 to 40 mg 18 consecutive patients who underwent 21 elective, direct-current countershock procedures for ventricular or supraventricular arrhythmias. Hypnosis lasting 15 30 minutes with complete amnesia the event induced on 20 occasions. One patient remained semiconscious and did recall three shocks up 400 w/sec. No significant changes heart rate, blood pressure, respiratory rate were noted following administration diazepam. The drug is...
Global ischemia in childhood often leads to poor neurologic outcomes, including learning and memory deficits. Using our novel model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR), we investigate the mechanism ischemia-induced cognitive deficits recovery. Memory is impaired seven days after juvenile CA/CPR completely recovers by 30 days. Consistent with this remarkable recovery not observed adults, hippocampal long-term potentiation (LTP) 7–14 CA/CPR, recovering This due replacement...
The incidence of stroke in children is 2.4 per 100,000 person-years and results long-term motor cognitive disability. In ischemic stroke, white matter (WM) frequently injured, but relatively understudied compared to grey injury. Previous research suggests that the cellular response WM injury different at ages. Little known about whether repair<i></i> mechanisms differ adults. We utilized a model focal determine oligodendrocyte (OL) juvenile adult mice....
Ischemic long-term potentiation (iLTP) is a form of synaptic plasticity that occurs in acute brain slices following oxygen-glucose deprivation. In vitro , iLTP can occlude physiological LTP (pLTP) through saturation mechanisms. We used our murine cardiac arrest and cardiopulmonary resuscitation (CA/CPR) model to produce global ischemia assess whether induced vivo contributing the functionally relevant impairment pLTP. Adult male mice were subjected CA/CPR, slice electrophysiology was...