NMDA receptor antagonists, such as (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), potently block glutamate-induced neuronal death in myriad vitro cell models and effectively attenuate ischemic damage vivo. In this report, a novel role for MK-801 other antagonists preconditioning neurons to withstand wide range of subsequent lethal insults is described. A brief 30 min exposure 0.1 microM MK-801, applied up 96 hr before "lethal" insult, protected primary...

The sensitivity of six fluorophores to glutathione (GSH) was evaluated in living rat cortical neuronal/glial mixed cultures during the first 23 days vitro (DIV). Four dyes require glutathione-S-transferase (GST) form a fluorescent conjugate, potentially conferring specificity for GSH: these included t-butoxycarbonyl-Leu-Met-7-amino-4-chloromethylcoumarin (CMAC), 7-amino-4-chloromethylcoumarin (CMAC-blue), monochlorobimane (MCB), and 5-chloromethylfluorescein diacetate (CMFDA). final two...

Cyclodextrins (CDs) are cyclic oligosaccharides composed of a lipophilic central cavity and hydrophilic outer surface. Some CDs capable extracting cholesterol from cell membranes can affect function receptors proteins localized in cholesterol-rich membrane domains. In this report, we demonstrate the neuroprotective activity some CD derivatives against oxygen-glucose deprivation (OGD), N-methyl-D-aspartic acid (NMDA) glutamate cortical neuronal cultures. Although all complexed with NMDA or...

Modern in vitro technologies for preclinical research, including organ-on-a-chip, organoids- and assembloid-based systems, have rapidly emerged as pivotal tools elucidating disease mechanisms assessing the efficacy of putative therapeutics. In this context, advanced models Parkinson's Disease (PD) offer potential to accelerate drug discovery by enabling effective platforms that recapitulate both physiological pathological attributes vivo environment. Although these systems often aim at...

Minocycline is a potent neuroprotective tetracycline in animal models of cerebral ischemia. We examined the protective properties chlortetracycline (CTC) and demeclocycline (DMC) showed that these two tetracyclines were also against glutamate-induced neuronal death vitro ischemia vivo. However, CTC DMC appeared to confer neuroprotection through unique mechanism compared with minocycline. Rather than inhibiting microglial activation caspase, suppressed calpain activities. In addition, only...

Transient exposure of rat cortical cultures to nonlethal oxygen-glucose deprivation (OGD preconditioning) induces tolerance otherwise lethal (OGD) or N-methyl-d-aspartate 24 h later. This study evaluates the role cytosolic and mitochondrial Ca 2+ -dependent cellular signaling. Mechanistic findings are placed in context with other models ischemic preconditioning known neurotoxic pathways within neurons. Tolerance OGD is suppressed by performing presence broad-scope catalytic antioxidants...

Tolerance to otherwise lethal cerebral ischemia in vivo or oxygen-glucose deprivation (OGD) vitro can be induced by prior transient exposure N-methyl-D-aspartic acid (NMDA): preconditioning this manner activates extrasynaptic and synaptic NMDA receptors require bringing neurons the "brink of death." We considered if stressful requirement could minimized stimulation primarily receptors. Subjecting cultured cortical prolonged elevations electrical activity tolerance OGD. Specifically, exposing...

Abstract Multiple‐quantum filtered (MQF) NMR offers the possibility of monitoring intracellular (IC) Na content in absence shift reagents (SR), provided that (i) contribution from IC to MQF spectrum is substantial and responds a change content, (ii) amplitude extracellular (EC) component remains constant during content. The validity basis for these conditions were examined isolated perfused rat hearts using SR‐aided SR‐free triple‐quantum (TQF) 23 NaNMR. Despite myocardial was only ˜1/70 EC...

Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control ATP-sensitive K + channel. Recent data suggest that intracellular sodium (Na i ) may also rely on glycolytically derived ATP; however, degree this dependence is unclear. To examine question, isolated, perfused rat hearts were exposed hypoxia, selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 μmol/l), glycolysis. Na and high-energy...

Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows power-law. Recent theoretical models have replicated power-law assuming the presence functionally feedforward connections (FFCs) in underlying dynamics system. Accordingly, generated chain activation that persists despite being embedded larger, massively recurrent circuit. However, it is unclear to what extent networks living neurons exhibit rely on FFCs. Here, we...

In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA) sodium (Nav) channels trigger excitotoxic neuron death. Na(+), Ca(++) H2O influx into affected neurons elicits swelling (increased cell volume) pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix). Though usually conflated in injured tissue, are distinct processes. Around an injury core, salvageable could be mildly swollen without yet having...

Preconditioning is defined as a range of stimuli that allow cells to withstand subsequent anaerobic and other deleterious conditions. While cell protection under preconditioning well established, this paper investigates the influence neuroprotective drugs, 4-aminopyridine bicuculline (4-AP/bic), on synaptic communication across broad network in vitro rat cortical neurons. Using permutation test, we evaluated cross-correlations extracellular spiking activity all pairs recording electrodes...

The feasibility of employing triple-quantum-filtered (TQF) or double-quantum-filtered (DQF) 23Na NMR spectra to monitor intracellular Na (Nain) content in isolated rat hearts perfused the absence a chemical-shift reagent (SR) was investigated. This necessitated characterization following: first, pool Nain represented by TQF (TQFin) spectrum; second, maximum extent which altered transverse relaxation times affect TQFin spectral amplitudes; and finally, situations for SR-free method can...

This study challenges the conventional view that metalloporphyrins protect cultured cortical neurons in models of cerebral ischemia by acting as intracellular catalytic antioxidants [superoxide dismutase (SOD) mimetics]. High SOD-active Mn(III)porphyrins meso-substituted with N,N'-dimethylimidazolium or N-alkylpyridinium groups did not against oxygen-glucose deprivation (OGD), although lower and -inactive para isomers protected N-methyl-D-aspartate (NMDA) exposure....

Excessive mu-calpain activation has been linked to several cellular pathologies including excitotoxicity and ischemia. In erythrocytes other non-central nervous system (CNS) cells, calpain is thought occur following a Ca2+-induced translocation of inactive cytosolic enzyme membranes subsequent autolysis. the present report, we show that transiently exposing primary rat cortical neurons lethal (50 microM) N-methyl-D-aspartic acid (NMDA) caused protracted activation, measured as increased...

This study determined how preconditioned neurons responded to oxygen-glucose deprivation (OGD) result in neuroprotection instead of neurotoxicity. Neurons using chronically elevated synaptic activity displayed suppressed elevations extracellular glutamate ([glutamateex ]) and intracellular Ca(2+) (Ca(2+) ) during OGD. The uptake inhibitor TBOA induced neurotoxicity, but at a longer OGD duration for cultures, suggestive delayed up-regulation transporter relative non-preconditioned cultures....