EFFECTS OF HYPERTONIC SOLUTIONS AND OF MERCURIC CHLORIDE ON THE UPTAKE OF [<sup>14</sup>C]GLUCOSE ANALOGUES BY RABBIT BRAIN

Spatz, Maria; Rap, Z. M.; Rapoport, Stanley I.; Klatzo, Igor

doi:10.1111/j.1365-2990.1976.tb00561.x

Cited by 12 publications

(3 citation statements)

References 15 publications

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“…The present results are consistent with the findings of Spatz et a1 [21] that the brain uptake index (BUI) for both 2-deoxyglucose and methylglucose is reversibly increased following intracarotid perfusion of hypertonic solutions in rabbits. The BUI for any given substance is determined within 15 seconds of its injection in tracer amounts and reflects the rate of entry of tracer into the brain at the blood-brain interface.…”

Section: Discussionsupporting

confidence: 93%

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Pappius

Savaki

Fieschi

et al. 1979

Annals of Neurology

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103

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The effects of osmotic opening of the blood-brain barrier (BBB) on local cerebral glucose utilization (LCGU) were studied in rats with the carbon 14-deoxyglucose method. The BBB was opened to Evans blue dye by unilateral carotid artery perfusion with hypertonic mannitol solution. (14C)-Deoxyglucose was injected 15 minutes or two to three hours later. Osmotic opening of the BBB resulted in focal areas of intense LCGU in affected areas of the perfused hemisphere. In the contralateral hemisphere, glucose utilization was diminished, especially in cerebral cortical areas. The effects were reversible. LCGU was normal in both hemispheres when permeability to Evans blue returned to normal two to three hours after carotid artery perfusion. In 3 of 5 experiments the administration of high doses of intravenous diazepam immediately following carotid artery perfusion with mannitol prevented an increase in LCGU in the perfused hemisphere but did not prevent lowering of LCGU in the contralateral hemisphere. Increased LCGU following osmotic opening of the BBB was not accompanied by a rise in local cerebral blood flow as measured by the iodoantipyrine method. Blood flow was, in fact, significantly decreased.

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Section: Discussionsupporting

confidence: 93%

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Pappius

Savaki

Fieschi

et al. 1979

Annals of Neurology

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103

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“…In the former model the concentration of pilocarpine necessary to induce a SE is 20 times lower than the dose required to induce SE with pilocarpine alone. Interestingly, molar concentration of lithium chloride has been used as a hyperos-molar compound to open BBB (Spatz et al, 1976). Therefore, the enhancing effect of LiCl could be attributed to the breakdown of BBB that subsequently increases the permeability to either pilocarpine or other ions/molecules that are usually excluded from brain parenchyma (Marchi and Janigro, unpublished observations).…”

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confidence: 99%

Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood–brain barrier permeability

et al. 2008

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Systemic application of the muscarinic agonist, pilocarpine, is commonly utilized to induce an acute status epilepticus that evolves into a chronic epileptic condition characterized by spontaneous seizures. Recent findings suggest that the status epilepticus induced by pilocarpine may be triggered by changes in the blood-brain barrier (BBB) permeability. We tested the role of the BBB in an acute pilocarpine model by using the in vitro model brain preparation and compared our finding with in vivo data. Arterial perfusion of the in vitro isolated guinea-pig brain with <1 mM pilocarpine did not cause epileptiform activity, but rather reduced synaptic transmission and induced steady fast (20-25 Hz) oscillatory activity in limbic cortices. These effects were reversibly blocked by co-perfusion of the muscarinic antagonist atropine sulfate (5 μM). Brain pilocarpine measurements in vivo and in vitro suggested modest BBB penetration. Pilocarpine induced epileptiform discharges only when perfused with compounds that enhance BBB permeability, such as bradykinin (n=2) or histamine (n=10). This pro-epileptic effect was abolished when the BBB-impermeable muscarinic antagonist atropine methyl bromide (5 μM) was co-perfused with histamine and pilocarpine. In the absence of BBB permeability enhancing drugs, pilocarpine induced epileptiform activity only after arterial perfusion at concentrations >10 mM. Ictal discharges correlated with a high intracerebral pilocarpine concentration measured by high pressure liquid chromatography.We propose that acute epileptiform discharges induced by pilocarpine treatment in the in vitro isolated brain preparation are mediated by a dose-dependent, atropine-sensitive muscarinic effect promoted by an increase in BBB permeability. Pilocarpine accumulation secondary to BBB permeability changes may contribute to in vivo ictogenesis in the pilocarpine epilepsy model. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 November 9. Published in final edited form as:Neuroscience. Pilocarpine is a non-selective muscarinic agonist (Maslanski et al., 1994) with a relatively high affinity for CNS muscarinic receptors (Hedlund and Bartfai, 1981) commonly utilized to develop an experimental model of temporal lobe epilepsy (Turski et al., 1989;Cavalheiro et al., 2006; but see Sloviter, 2005). In different animal species, i.p. injection of pilocarpine induces a convulsive status epilepticus (SE; i.e. sub-continuous generalized seizures that recur for several hours), followed within 2 weeks by a chronic epileptic condition that mimics human temporal lobe epilepsy (Cavalheiro et al., 2006). The initial SE is thought to be triggered by a cholinergic activation of excitatory neurons in specific brain regions that include limbic cortices. Such an effect is supposedly mediated by micro-molar concentrations of pilocarpine, since this drug shows a relatively poor brain penetration (Omori et al., 2004). Although studies directly assessing pilocarpine penetration across the ...

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“…Six animals injected with Urea, as before, plus 50 ng/kg/min norepinephrine had significantly increased values for cerebral blood flow and oxygen and glucose consumption compared to baseline values. Spatz et al (1976) perfused New Zealand rabbits through the intracarotid artery with hypertonic 2 and 3 M Urea and 0.3 M Urea adjusted to pH 7.4. The animals had increased brain uptake indexes of glucose analogues, while isotonic Urea was without effect.…”

Section: Other Urea Biological Activitiesmentioning

confidence: 99%

Final Report of the Safety Assessment of Urea1

2005

Int J Toxicol

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Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic aromatic compounds which function in cosmetics primarily as hair and skin conditioning agents. Niacinamide is used in around 30 cosmetic formulations including shampoos, hair tonics, skin moisturizers, and cleansing formulations. Niacin is used in a few similar product types. The concentration of use of Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders and sprays. Niacin concentrations of use range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in paste masks (mud packs). Both ingredients are accepted for use in cosmetics in Japan and the European Union. Both are GRAS direct food additives and nutrient and/or dietary supplements. Niacinamide may be used in clinical treatment of hypercholesteremia and Niacin in prevention of pellegra and treatment of certain psychological disorders. Both ingredients are readily absorbed from skin, blood, and the intestines and widely distribute throughout the body. Metabolites include N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is primarily through the urinary tract. While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic. Short-term oral, parenteral, or dermal toxicity studies did not identify significant irreversible effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation, was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in actual formulations produced mostly non-irritant reactions, with only some marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide in rabbits produced only marginal irritation. Skin sensitization tests of Niacinamide at 5% during induction and 20% during challenge were negative in guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or without metabolic activation. Niacinamide and Niacin at 2 mg/ml were negative in a chromosome aberration test in Chinese hamster ovary cells, but did produce large structural chromosome aberrations at 3 mg/ml. Niacinamide induced sister chromatid exchanges in Chinese hamster ovary cells, but Niacin did not. Under certain circumstances, Niacinamide can cause an increase in unscheduled DNA synthesis in human lymphocytes treated with UV or a nitrosoguanidine compound. Niacinamide itself was not carcinogenic when administered (1%) in the drinking water of mice. No data on the carcinogenic effect of Niacin were available. Niacinamide can moderate the induction of tumors by established carcinogens. Niacinamide in combination with streptozotocin (a nitrosourea compound) or with heliotrine (a pyrrolizidine alkaloid), produced pancreatic islet tumors. On the other hand, Niacinamide reduced the renal adenomas produced by streptozotocin; and intestinal and bladder tumors induced by a preparation of bracken fern. Niacinamide evaluated in in vitro test systems did affect development, but Niacinamide re...

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EFFECTS OF HYPERTONIC SOLUTIONS AND OF MERCURIC CHLORIDE ON THE UPTAKE OF [¹⁴C]GLUCOSE ANALOGUES BY RABBIT BRAIN

Cited by 12 publications

References 15 publications

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood–brain barrier permeability

Final Report of the Safety Assessment of Urea1

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EFFECTS OF HYPERTONIC SOLUTIONS AND OF MERCURIC CHLORIDE ON THE UPTAKE OF [14C]GLUCOSE ANALOGUES BY RABBIT BRAIN

Cited by 12 publications

References 15 publications

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization

Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood–brain barrier permeability

Final Report of the Safety Assessment of Urea1

Contact Info

Product

Resources

About

EFFECTS OF HYPERTONIC SOLUTIONS AND OF MERCURIC CHLORIDE ON THE UPTAKE OF [¹⁴C]GLUCOSE ANALOGUES BY RABBIT BRAIN