A5056727069- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurological Disease Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
- Neurological Disorders and Treatments
- Biochemical effects in animals
- Barrier Structure and Function Studies
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac electrophysiology and arrhythmias
- Cerebrovascular and Carotid Artery Diseases
- Metabolism and Genetic Disorders
- Cardiovascular Health and Disease Prevention
- Neuropeptides and Animal Physiology
- ATP Synthase and ATPases Research
- Neuroscience of respiration and sleep
- RNA Interference and Gene Delivery
- Cerebrovascular and genetic disorders
- MRI in cancer diagnosis
- Cellular transport and secretion
- Adipokines, Inflammation, and Metabolic Diseases
- Olfactory and Sensory Function Studies
- Sodium Intake and Health
- Antioxidant Activity and Oxidative Stress
University of Calgary
2015-2025
Allen Institute for Brain Science
2023
Ontario Brain Institute
2020
University of Szeged
2004-2015
Wake Forest University
2009-2013
Tulane University
2013
Abstract Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in efficacy are highly sensitive to stress, yet whether astrocyte bioenergetic control synapses contributes stress-impaired plasticity is unclear. Here we show mice that stress constrains shuttling glucose lactate through networks, creating a barrier for neuronal access an astrocytic reservoir hippocampus neocortex, compromising long-term potentiation. Impairing delivery substrates by...
Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between degree adiposity cognitive dysfunction elderly. In this review, pathophysiological roles microvascular mechanisms, including impaired endothelial function neurovascular coupling responses, rarefaction, blood-brain barrier disruption genesis impairment geriatric obesity considered. The potential contribution adipose-derived factors fundamental...
Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) satisfy regional energy demand. Ca
Mitochondrial depolarization after ATP-sensitive potassium channel activation has been shown to induce cerebral vasodilation by the generation of calcium sparks in smooth muscle. It is unclear, however, whether mitochondrial endothelial cells capable promoting releasing vasoactive factors. Therefore, we studied effect activators, BMS-191095 (BMS) and diazoxide, on endothelium-dependent vasodilation.Diameter studies isolated rat arteries showed BMS- diazoxide-induced vasodilations that were...
Despite increased risk of a recurrent stroke following minor stroke, information is minimal regarding the interaction between injurious mild cerebral ischemic episodes and possible treatments which might be effective. The aim current study was to investigate whether resveratrol, nutritive polyphenol with promising cardio- neuro- protective properties, could ameliorate associated brain damage. Experiments in adult rats demonstrated that followed by second ischemia exacerbated damage, and,...
Very-low-frequency oscillations in microvascular diameter cause fluctuations oxygen delivery that are important for fueling the brain and functional imaging. However, little is known about how regulates ongoing cerebral blood flow. In mouse rat cortical slice arterioles, we find selectively enhancing tone sufficient to recruit a TRPV4-mediated Ca2+ elevation adjacent astrocyte endfeet. This endfoot signal triggers COX-1-mediated "feedback vasodilators" limit extent of evoked...
Abstract Dynamic changes in astrocyte Ca 2+ are recognized as contributors to functional hyperemia, a critical response increased neuronal activity mediated by process known neurovascular coupling (NVC). Although the role of glutamatergic signaling this has been extensively investigated, impact behavioral state, and release behavior-associated neurotransmitters, such norepinephrine serotonin, on dynamics hyperemia have received less attention. We used two-photon imaging barrel cortex awake...
Our objective was to investigate the mitochondrial dynamics following oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. We documented changes morphology, protein expression, and DNA levels mitochondria OGD examined roles of fission [dynamin-related 1 (Drp1), protein-1 (Fis1)] fusion [mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), optic atrophy-1 (OPA1)] proteins on biogenesis morphogenesis. tested effects two Drp1 blockers [15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2) Mitochondrial...
Neuronal hyperactivity is an early primary dysfunction in Alzheimer's disease (AD) humans and animal models, but effective neuronal hyperactivity-directed anti-AD therapeutic agents are lacking. Here we define a previously unknown mode of ryanodine receptor 2 (RyR2) control AD progression. We show that single RyR2 point mutation, E4872Q, which reduces open time, prevents hyperexcitability, hyperactivity, memory impairment, cell death, dendritic spine loss severe early-onset mouse model...
Abstract Ryanodine receptor 2 (RyR2) is abundantly expressed in the heart and brain. Mutations RyR2 are associated with both cardiac arrhythmias intellectual disability. While mechanisms of RyR2-linked well characterized, little known about mechanism underlying RyR2-associated Here, we employed a mouse model expressing green fluorescent protein (GFP)-tagged specific GFP probe to determine subcellular localization hippocampus. GFP-RyR2 was predominantly detected soma dendrites, but not...
Ca 2+ -dependent pathways in neurons and astrocyte endfeet initiate changes arteriole diameter to regulate local brain blood flow. Whether there exists a threshold of synaptic activity which is controlled independent remains unclear. We used two-photon fluorescence microscopy examine synaptically evoked synthetic or genetic indicator signals around penetrating arterioles acute slices the rat neocortex. discovered below vasodilation occurred absence but with consistent neuronal transients,...
Effects of insulin on cerebral arteries have never been examined. Therefore, we determined cerebrovascular actions in rats. Both PCR and immunoblot studies identified receptor expression cultured microvascular endothelial cells (CMVECs). Diameter measurements (% change) isolated rat showed a biphasic dose response to with an initial vasoconstriction at 0.1 ng/mL (−9.7%±1.6%), followed by vasodilation 1 100 (31.9%±1.4%). Insulin also increased cortical blood flow vivo (30%±8% 120 ng/mL) when...
Previously, we have shown that IR impairs the vascular reactivity of major cerebral arteries ZO rats prior to occurrence Type-II diabetes mellitus. However, functional state microcirculation in cortex is still being explored.We tested local CoBF responses 11-13-week-old (n = 31) and control ZL 32) several stimuli measured by LDF using a closed cranial window setup.The topical application 1-100 μm bradykinin elicited same degree elevation both groups. There was no significant difference...
Insulin resistance (IR) impairs cerebrovascular responses to several stimuli in Zucker obese (ZO) rats. However, cerebral artery after subarachnoid hemorrhage (SAH) have not been described IR. We hypothesized that IR worsens vascular reactions a mild SAH. Hemolyzed blood (300 μl) or saline was infused (10 μl/min) into the cisterna magna of 11–13-wk-old ZO ( n = 25) and lean (ZL) rats 25). One day later, dilator basilar (BA) its side branch (BA-Br) acetylcholine (ACh, 10 −6 M), cromakalim −7...