Effect of acetyl-l-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat — study by 13P- and 1H-NMR spectroscopy

Aureli, Tommaso; Miccheli, Alfredo; Cocco, Maria Enrica Di; Ghirardi, Orlando; Giuliani, Alessandro; Ramacci, M. T.; Conti, Filippo

doi:10.1016/0006-8993(94)90013-2

Cited by 68 publications

(41 citation statements)

References 36 publications

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“…4-10, [27][28][29][30] However, the finding of higher lactate concentrations in all M/C extractions could indicate that the technique does not inactivate tissue enzymes as efficiently as PCA. On the other hand, the relatively high PCr/Cr ratio (PCA, 0.59 AE 0.015; M/C, 0.56 AE 0.017; mean AE SEM) would suggest that enzyme inactivation has been relatively efficient.…”

Section: Tissue Extractionmentioning

confidence: 81%

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy

et al. 2002

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Analysis of brain metabolites by a wide range of analytical techniques is typically achieved using biochemical extraction methodologies that require either two separate samples or two separate extraction steps to prepare both aqueous and organic metabolite fractions. However there are a number of brain pathologies in which both aqueous metabolite and lipid changes occur so that a simultaneous extraction of both fractions would be valuable. The methanol-chloroform (M/C) technique enables extraction of both aqueous metabolites and lipids simultaneously. It is already well established for lipid extraction of cells and tissue but its efficiency and reproducibility for extraction of aqueous metabolites is unknown. Therefore, we compared the aqueous metabolite yield and the reproducibility of the M/C method to the commonly used perchloric acid (PCA) method, using 1H-NMR spectroscopy of adult rat brain and purified rat astrocyte culture extracts. The results indicate that M/C is a superior technique for aqueous metabolite extraction from both brain tissue and cells when compared to the PCA method. The M/C extraction technique enables the simultaneous extraction of both lipids and aqueous metabolites from a single sample using small solvent-volumes, making it well suited for NMR investigations of both tissues and cells.

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Section: Tissue Extractionmentioning

confidence: 81%

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy

et al. 2002

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“…No study has examined dose-response relationships, thus it remains unknown whether greater neuroprotection would be observed in the rat CCI model with doses higher than 100 mg/kg or whether lower doses would also be effective. The present study and the two other studies employing rat models all used 2 or more doses of ALCAR [6,33,46], whereas the canine study employed 1 early intravenous bolus administration [21]. It is not known how many doses of ALCAR are optimal for neuroprotection after TBI.…”

Section: Discussionmentioning

confidence: 99%

“…Our group and others have shown that the maximal activity and/or immunoreactivity of PDHC subunits is reduced within the first few hours after both global cerebral ischemia and TBI [5,6,7,8,10,11,12,13,14]. ALCAR can supply acetyl CoA as a substrate for brain energy metabolism, and can both improve brain ATP levels and decrease brain lactate after injury [21,30,46]. Furthermore, administration of 3-hydroxybutyrate, another substrate that enters the metabolism at the level of acetyl CoA, improves ATP production after TBI in adult rats [57].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…ALCAR was administered 4 times intraperitoneally at a dose of 100 mg/kg at 1, 4, 12 and 23 h after the CCI [46]. The dosing schedule by Aureli et al [46] was used since it led to a complete recovery of brain ATP levels at 2–48 h after injury in a rat stroke model. Previous findings in our laboratory also demonstrated neuroprotection with 100 mg/kg ALCAR in an adult rat stroke model and in an adult canine cardiac arrest model [21,33].…”

Section: Discussionmentioning

confidence: 99%

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Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Scafidi

Racz²,

Hazelton³

et al. 2010

Dev Neurosci

112

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Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-L-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21–22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3–7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was significantly smaller in ALCAR-treated than in vehicle-treated TBI rats (14 ± 5% vs. 28 ± 6%; p < 0.05). We conclude that treatment with ALCAR during the first 24 h after TBI improves behavioral outcomes and reduces brain lesion volume in immature rats within the first 7 days after injury.

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Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders

Tarnopolsky

Beal

2001

Annals of Neurology

225

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Substantial evidence indicates that bioenergetic dysfunction plays either a primary or secondary role in the pathophysiology of cell death in neurodegenerative and neuromuscular disorders, and even in normal aging. Agents that ameliorate bioenergetic defects may therefore be useful in therapy. Creatine, which increases muscle and brain phosphocreatine concentrations, and may inhibit the activation of the mitochondrial permeability transition, protects against neuronal degeneration in transgenic murine models of amyotrophic lateral sclerosis and Huntington's disease and in chemically mediated neurotoxicity. Initial studies of creatine use in humans appear promising; however, further long-term, well-designed trials are needed. Coenzyme Q10, Gingko biloba, nicotinamide, riboflavin, carnitine, lipoic acid, and dichloroacetate are other agents which may have beneficial effects on energy metabolism, but the preclinical and clinical evidence for efficacy in neurological diseases remains limited. These compounds are widely used as dietary supplements; however, they must be subjected to rigorous evaluation through randomized, double-blinded trials to establish efficacy, cost-effectiveness and safety in neurological disorders.

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Effect of acetyl-l-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat — study by 13P- and 1H-NMR spectroscopy

Cited by 68 publications

References 36 publications

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders

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Effect of acetyl-l-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat — study by 13P- and 1H-NMR spectroscopy

Cited by 68 publications

References 36 publications

A comparison of cell and tissue extraction techniques using high‐resolution 1H‐NMR spectroscopy

A comparison of cell and tissue extraction techniques using high‐resolution 1H‐NMR spectroscopy

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders

Contact Info

Product

Resources

About

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy

A comparison of cell and tissue extraction techniques using high‐resolution ¹H‐NMR spectroscopy