A5076649568- Neuroscience and Neuropharmacology Research
- Anesthesia and Neurotoxicity Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal and fetal brain pathology
- Ion channel regulation and function
- Traumatic Brain Injury and Neurovascular Disturbances
- Cholinesterase and Neurodegenerative Diseases
- Medicinal Plants and Neuroprotection
- Nicotinic Acetylcholine Receptors Study
- Biochemical effects in animals
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Neurological Disease Mechanisms and Treatments
- Calcium signaling and nucleotide metabolism
- Sepsis Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Photoreceptor and optogenetics research
- Sleep and Wakefulness Research
- Ion Channels and Receptors
- Cardiac Arrest and Resuscitation
- Computational Drug Discovery Methods
- Thermal Regulation in Medicine
- Intensive Care Unit Cognitive Disorders
- Alzheimer's disease research and treatments
The Ohio State University
2022-2025
Neurological Surgery
2021-2025
University of Colorado Anschutz Medical Campus
2016-2023
University of Colorado Denver
2014-2022
The Medical Center of Aurora
2022
University of Colorado System
2020
The University of Texas at El Paso
2012-2014
The University of Texas at San Antonio
2003-2004
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...
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...
Introduction: Ischemic stroke is one of the leading causes death in United States and a known risk factor for Alzheimer’s Disease (AD) development. One characterizations AD accumulation β-amyloid peptide due to proteolysis Amyloid Precursor Protein (APP) by protein Presenilin 1 (PS1) among others. In APP/PS1 mice, which contain an additional human copy APP PS1, 15-minute Middle Cerebral Artery Occlusion (MCAO) model was developed. Here we investigate effects increased on motor coordination...
Introduction: Post-Stroke Cognitive Impairment (PSCI) is increasingly recognized as a major factor in long-term disability. Therefore, new therapies that enhance post-stroke brain function (plasticity) are appealing translational research. Activation of the cation channel TRPM2 after middle cerebral artery occlusion (MCAO) induces PSCI-like symptoms, such memory impairment and deficits Long-Term Potentiation (LTP). Determining mediator chronic activation may implicate novel contributor to...
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...
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...
Here, we use optogenetics and chemogenetics to investigate the contribution of paraventricular thalamus (PVT) nucleus accumbens (NAc) pathway in aversion heroin relapse two different self-administration models rats. In one model, rats undergo forced abstinence home cage prior testing, other, they extinction training, a procedure that is likened cognitive behavioral therapy. We find PVT→NAc both sufficient necessary drive seeking after abstinence, but not extinction. The ability reduce this...
Excitotoxicity and the concurrent loss of inhibition are well-defined mechanisms driving acute elevation in excitatory/inhibitory (E/I) balance neuronal cell death following an ischemic insult to brain. Despite high prevalence long-term disability survivors global cerebral ischemia (GCI) as a consequence cardiac arrest, it remains unclear whether E/I imbalance persists beyond phase negatively affects functional recovery. We previously demonstrated sustained impairment potentiation (LTP)...
Abstract Global cerebral ischemia following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes injury to hippocampal CA1 pyramidal neurons impairs cognition. Small conductance Ca 2+ ‐activated potassium channels type 2 (SK2), expressed in neurons, have been implicated as potential protective targets. Here we showed that, mice, long‐term potentiation (LTP) was impaired early 3 h after recovery from CA/CPR LTP remained for at least 30 days. Treatment with the SK2 channel agonist...
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...
Post-stroke cognitive impairment and dementia (PSCID) affects many survivors of large vessel cerebral ischemia. The molecular pathways underlying PSCID are poorly defined but may overlap with neurodegenerative pathophysiology. Specifically, synaptic dysfunction after stroke be directly mediated by alterations in the levels amyloid beta (Aβ), peptide that accumulates brains Alzheimer’s disease (AD) patients. In this study, we use transient middle artery occlusion (MCAo) model young adult mice...
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 Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological inhibition the neuroprotective peptide tatCN19o interfered in mice only mildly transiently (for less than 1 h) did not at all reverse These results were obtained ≥500-fold...
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...
Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced adolescent nicotine exposure. In order understand the underlying mechanisms that contribute developmental differences in use, this study compared cholinergic transmission during exposure withdrawal naïve adult rats (1) (2) were pre-exposed adolescence. The first extracellular levels acetylcholine (ACh) nucleus accumbens (NAc) precipitated using...
Preclinical studies have established that neonatal exposure to contemporary sedative/hypnotic drugs causes neurotoxicity in the developing rodent and primate brains. Our group recently reported novel neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) induced effective hypnosis both adult rodents but did not cause significant vulnerable brain regions such as subiculum, an output region of hippocampal formation particularly sensitive commonly used sedatives/hypnotics....