Search results for "Neuroprotective Agent"
showing 10 items of 156 documents
Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury …
2019
Background.Xenon is a noble gas with neuroprotective properties. We previously showed that xenon improves short and long-term outcomes in young adult mice after controlled cortical impact (CCI). This is a follow-up study investigating xenon’s effect on very long-term outcome and survival. Methods.C57BL/6N (n=72) young adult male mice received single CCI or sham surgery and were treated with either xenon (75%Xe:25%O2) or control gas (75% N2:25%O2). The outcomes used were: 1) 24-hour lesion volume and neurological outcome score; 2)contextual fear-conditioning at 2 weeks and 20 months; 3) corpus callosum white matter quantification; 4) immunohistological assessment of neuroinflammation and neu…
BRAIN-TARGETED SOLID LIPID NANOPARTICLES CONTAINING RILUZOLE: PREPARATION, CHARACTERIZATION AND BIODISTRIBUTION
2009
Aim: Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Materials & method: Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodi…
Mildronate, the inhibitor of l-carnitine transport, induces brain mitochondrial uncoupling and protects against anoxia-reoxygenation
2013
Abstract The preservation of mitochondrial function is essential for normal brain function after ischaemia-reperfusion injury. l -carnitine is a cofactor involved in the regulation of cellular energy metabolism. Recently, it has been shown that mildronate, an inhibitor of l -carnitine transport, improves neurological outcome after ischaemic damage of brain tissues. The aim of the present study was to elucidate the mitochondria targeted neuroprotective action of mildronate in the model of anoxia-reoxygenation-induced injury. Wistar rats were treated daily with mildronate ( per os ; 100 mg/kg) for 14 days. The acyl-carnitine profile was determined in the brain tissues. Mitochondrial respirati…
NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhag…
2007
Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectropho…
Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.
2014
The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) e…
The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats.
2012
For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5 m/sec, 2.5 mm). To study the effects of lactate tre…
Administration of transforming growth factor-α reduces infarct volume after transient focal cerebral ischemia in the rat
2001
Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-α (TGF-α was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-α (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser-Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-α o…
Improvement of the circulatory function partially accounts for the neuroprotective action of the phytoestrogen genistein in experimental ischemic str…
2012
Abstract We tested the hypothesis that the phytoestrogen genistein protects the brain against ischemic stroke by improving the circulatory function in terms of reduced production of thromboxane A2 and leukocyte–platelet aggregates, and of preserved vascular reactivity. Ischemia-reperfusion (90 min-3 days, intraluminal filament) was induced in male Wistar rats, and functional score and cerebral infarct volume were the end points examined. Genistein (10 mg/kg/day) or vehicle (β-cyclodextrin) was administered at 30 min after ischemia or sham-operation. Production of thromboxane A2 and leukocyte–platelet aggregates, as well as reactivity of carotid artery to U-46619 (thromboxane A2 analogue) an…
Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats.
1998
Background and Purpose —The lipid peroxidation inhibitor U-101033E was examined for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen saturation (HbS o 2 ), and neuronal damage. Methods —Fifteen minutes of global cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension. Wistar rats (n=25) were randomized to receive vehicle (n=9) or 40 mg/kg U-101033E (n=9) intraperitoneally during 2 hours of reperfusion. A sham group (n=7) had neither ischemia nor therapy. Histology was evaluated 7 days after ischemia. Results —During late hyperperfusion (at 17 minutes), vehicle-treated animals had a higher ( P =0.044) cortical tissue HbS o 2 (72.0±1.4%) than di…
[3H]-DA release evoked by low pH medium and internal H+ accumulation in rat hypothalamic synaptosomes: involvement of calcium ions
2003
The pH fluctuations have been often interpreted as an insufficient regulation or as a consequence of the onset of pathological events, such as ischemia, in which a significant decrease in pH levels occurs. Neurotransmitter release appears to be affected by pH drop significantly. In this study, we investigated the effect of an extracellular and an intracellular acidification on tritiated dopamine release ([3H]-DA release), from superfused rat hypothalamic synaptosomes. When compared to basal release, extracellular acidification, due to a reduction in the external pH of the nominally carbonic-free superfusion media, provoked a significant increase in [3H]-DA release that showed a sensitivenes…