Cerebrospinal fluid choline levels in Parkinson's disease.
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Aged↗
Biomedical subjects
A Beley
Publications and source records attributed to A Beley.
Biphasic striatal acetylcholine release during and after transient cerebral ischemia in gerbils.
Acetylcholine (ACh) release into the extracellular space was measured by HPLC with electrochemical detection after in vivo intracerebral microdialysis in the striatum of gerbils subjected to 15 min of bilateral carotid artery occlusion followed by 5 h of recirculation. Tissue ACh and choline (Ch) contents were also determined during ischemia and after 5, 30, 60, and 120 min of reflow. Fifteen minutes of ischemia led to a significant transient increase in extracellular ACh concentration (threefold after 7.5 min of ischemia) concomitant with a reduced endogenous ACh level (-62%) and increased tissue Ch content (ninefold). Recirculation significantly reduced the ACh release during the early period of reflow (-50% vs. basal level), followed by a significant increase in ACh release between 1 and 3 h of reflow (45-55% vs. basal level) and subsequent normalization. Simultaneously, a "rebound" of tissue ACh level occurred in the early period of reflow (fourfold vs. ischemic value), followed by gradual normalization after 2 h of reperfusion, whereas a rapid decrease in tissue Ch levels was found after 30 min of reflow. These findings represent the first demonstration of a biphasic release of ACh during ischemia and reperfusion, as assessed by intracerebral microdialysis in gerbils.
Acetylcholine↗
Alpha-methyl-para-tyrosine pretreatment protects from striatal neuronal death induced by four-vessel occlusion in the rat.
Rats were treated with alpha-methyl-para-tyrosine (AMT, 250 mg/kg, i.p), an hydroxylase inhibitor, in order to decrease brain levels of catecholamines. Six hours later, when cerebral dopamine (DA) and norepinephrine were reduced by about 80%, a transient forebrain ischemia of 30 min duration was induced by four-vessel occlusion technique. Evaluation of brain damage 72 hours after ischemia showed that AMT treatment significantly decreased neuronal necrosis in the striatum but had no cytoprotective effect in the CA1 sector of the hippocampus and in the neocortex. AMT treatment reduced mortality within the ischemic period but did not affect either the mortality within the recirculation period or the postischemic neurologic deficit. These results suggest that the striatal cytoprotective effect of AMT is linked to cerebral DA depletion and that excessive release of DA during ischemia or dopaminergic hyperactivity during recirculation play a detrimental role in the development of ischemic cell damage in the striatum.
Animals↗
Post-ischemic regional changes in acetylcholine synthesis following transient forebrain ischemia in gerbils.
The synthesis rate of brain acetylcholine (ACh) was estimated 30 min and 5 days following transient forebrain ischemia performed by 10 min bilateral carotid occlusion in gerbils. ACh synthesis was evaluated from the conversion of radiolabeled choline (Ch) into ACh after an i.v. administration of [methyl-3H]Ch. Endogenous and labeled Ch and ACh were quantified by HPLC. The synthesis rate of Ach was significantly decreased following 30 min of recirculation. The reductions reached 55.4% in the hippocampus, 51.2% in the cerebral cortex and 44.4% in the striatum. Five days after ischemia, the values returned to normal in the cerebral cortex and in the striatum, while ACh synthesis remained selectively lowered (-30.4%, p less than 0.01) in the hippocampus. These cholinergic alterations may account for both early and delayed post-ischemic behavioral and mnesic deficits.
Acetylcholine↗
Cerebral ischemia: changes in brain choline, acetylcholine, and other monoamines as related to energy metabolism.
The relationship of cerebral neurotransmitters acetylcholine (ACh), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT) to the energy state of the brain was examined in mice at various times following complete ischemia produced by decapitation, in gerbils submitted to transient global ischemia (10 min bilateral carotid artery occlusion, 5 or 30 min recirculation), and in rats 24 hr after irreversible microembolism. Ischemia caused significant reductions in brain monoamine concentrations. The alterations in NA, DA, and 5HT levels persisted during recirculation and were unrelated to energy restoration. They were accompanied by an increase in the concentrations of related metabolites, suggesting that synthesis was unable to compensate for the release of the transmitters at early post-ischemic time periods. As described for the catecholamines and 5HT, ischemia resulted in a significant decrease in ACh level, but recirculation was associated with a rapid increase in ACh concentration. Impaired synthesis and/or increased release of ACh can be responsible for the decrease in ACh concentration during ischemia. Early post-ischemic elevation of ACh may be related to the large increase in brain choline brought about by ischemia.
Acetylcholine↗
Effect of oxotremorine, physostigmine, and scopolamine on brain acetylcholine synthesis: a study using HPLC.
The synthesis rate of brain acetylcholine (ACh) was estimated in mice following i.v. administration of [3H]choline (Ch). The measurements were performed 1 min after the tracer injection, using the [3H]ACh/[3H]Ch specific radioactivity ratio as an index of ACh synthesis rate. Endogenous and labeled Ch and ACh were quantified using HPLC methodology. Oxotremorine and physostigmine (0.5 mg/kg, i.p.) increased the steady state concentration of brain ACh by + 130% and 84%, respectively and of Ch by + 60% (oxotremorine); they decreased ACh synthesis by 62 and 55%, respectively. By contrast, scopolamine (0.7 mg/kg, i.p.) decreased the cerebral content of Ch by - 26% and of ACh by - 23% without enhancing the synthesis of ACh. The results show the utility of HPLC methodology in the investigation of ACh turnover.
Acetylcholine↗
Turnover rate of brain acetylcholine using HPLC separation of the transmitter.
A simple, reliable method was developed for measuring brain acetylcholine (ACh) turnover using HPLC methodology. Mice were injected intravenously with [3H]choline ([3H]Ch), and the turnover rate of ACh was calculated from the formation of [3H]ACh. Ch and ACh were separated from phosphorylcholine and from other radioactive compounds using tetraphenylboron extraction and counterion/reverse-phase chromatography. Endogenous Ch and ACh were quantified electrochemically through hydrogen peroxide production in a postcolumn reactor containing covalently bonded ACh esterase and Ch oxidase. Labeled Ch and ACh were quantified in the same sample by collecting the chromatographic fractions for radioactive content determinations. The method is rapid, well adapted to large series, and highly reproducible, with recoveries of 72.1% for Ch and 79.3% for ACh. The turnover value in mouse cerebral hemispheres was 16.02 nmol g-1 min-1 and decreased to 9.94 nmol g-1 min-1 in mice treated with oxotremorine.
Acetylcholine↗
[Vascular reactivity to carbon dioxide in the acute stage of cerebral infarction in rats].
The effect of CO2 on the cerebral circulation was assessed 24 hours after induction of unilateral brain infarction performed in the rat by injecting radioactive calibrated 50 microns microspheres into the internal carotid artery. The intracerebral distribution of microspheres and regional cerebral blood flow were measured bilaterally in 8 brain regions. In control rats, increase in arterial pCO2 to about 80 mm Hg resulted in 30 to 100% increase in flow according to the area. Cerebral blood flow was also enhanced in the embolized rats, the basal values being multiplied by a factor 1.7 in the embolized hemisphere and by a factor 1.8 in the contralateral hemisphere. These results do not provide evidence for the existence of a "steal" phenomenon between the non infarcted and infarcted hemispheres.
Animals↗
Influence of blood pressure on blood-brain barrier function in brain ischemia.
The influence of systemic blood pressure on blood-brain barrier leakage and hemorrhage in brain ischemia was evaluated in Sprague-Dawley rats with blood pressures at the lower and upper limit normally found in these animals when anesthetized on 70% N2O:30% O2. 24 h after unilateral cerebral microembolization - when significant increases in water content and barrier permeability and decrease in blood flow is present - the extravasation of Evans Blue-albumin and inulin as well as hemorrhage in the infarcted brain area was considerably more prominent in animals with the higher blood pressure. The findings imply that attempts to elevate pressure, as well as subacute surgical circulatory reconstruction to increase perfusion of an ischemic area, may be potentially harmful.
Animals↗
Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration.
Rats were treated with MnCl2 X 4H2O (1 mg/100 g/day, i.p.) for a period of 4 months. The turnover of dopamine (DA) and norepinephrine (NE) was measured in several brain regions (brain stem, hypothalamus, corpus striatum and "rest of the brain") by the decay in endogenous DA and NE after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine. Monoamine oxidase (MAO) activity and manganese levels were also estimated. Manganese treatment produced a decrease in DA level and turnover in the corpus striatum but not in the rest of the brain. An increase in contents of NE was observed both in the brain stem and hypothalamus. NE turnover was found to be increased in the brain stem, decreased in the hypothalamus and unaltered in the rest of the brain. MAO activity was not significantly altered in all the brain regions studied. These results which show that chronic administration of manganese may cause regionally different changes in catecholamine turnover were discussed in relation to the accumulation of manganese in the brain regions and to other metabolic changes associated with manganese toxicity.
Animals↗
[Cerebral protection by gamma-butyrolactone after induction of experimental ischemia in the rat].
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4-Butyrolactone↗
Cerebral microembolization in the rat: changes in blood-brain barrier permeability and cerebral blood flow as related to the degree of ischemia.
Unilateral cerebral microembolism was performed in the rat by injecting calibrated, 50 micrometers in diameter, carbonized microspheres into the internal carotid artery. The events that follow brain ischemia due to cerebral embolization were studied by the analysis of the blood-brain barrier (BBB) function, the degree of regional cerebral blood flow (CBF) and the development of brain edema. Two hours after embolization there was no change in the brain water content. The local CBF (14C-ethanol technique) was only reduced in the ipsilateral hemisphere. Twenty-four hours after embolization the brain water content was increased significantly in the ipsilateral, but not in the contralateral hemisphere. Local CBF further decreased in the ipsilateral hemisphere and a reduction in flow was also observed in the contralateral hemisphere. Embolization led to an increase in the BBB permeability, analysed as regional penetrability of 3H-dextran and of Evans blue-albumin complexes, which was restricted to the side of the injection of the microspheres.
Animals↗
Catecholamine levels and turnover during brain ischemia in the rat.
Unilateral brain ischemia was induced in the rat by injecting radioactive microspheres into the left internal carotid artery. The microspheres were mainly distributed in the left cerebral hemisphere which contained 8 to 10 times more microspheres than the contralateral hemisphere. Embolization caused dopamine (DA) and noradrenaline (NA) depletion only in the left hemisphere. NA levels were already reduced 2 hours after injury while DA was still unaltered after 6 hours. A 30--40% depletion was observed for the two amines after 24 hours. Catecholamine turnover was estimated by measuring the amine depletion after synthesis inhibition with alpha-methyl-p-tyrosine. During the first 2 hours following embolization, DA and NA depletions were slightly increased only in the left hemisphere, indicating an increase in catecholamine efflux. At times 24 hours, an important retardation in amine disappearance after synthesis inhibition was found for DA and NA in the left hemisphere and to a lesser extent for DA in the right hemisphere, suggesting a reduction of the physiological activity of catecholaminergic neurons. These biochemical alterations can be related to the post-stroke behavioural changes of the embolized animals which exhibited an initially increased motor activity followed by a lethargic state.
Animals↗
Time-dependent changes in the rate of noradrenaline synthesis in various rat brain areas during cold exposure.
The synthesis of noradrenaline (NA) was studied in vivo in the hypothalamus, the brain stem and the "rest of brain" of rats which were exposed to 4 degrees C for 0.5, 2.5 or 24 h. The rate of NA synthesis was estimated 30 min after an i.v. injection of 3H tyrosine (TY) by evaluation of the ratio: 3H-NA specific activity/3H-TY specific activity. Cold exposure did not have the same effect on NA synthesis in the three brain areas. In the hypothalamus, the rate of NA synthesis was increased by a factor of 1.7 and 2 after 0.5 and 2.5 h of cold exposure, respectively and returned to control values after 24 h of cold exposure. In the brain stem, NA synthesis was enhanced by a factor of 1.5 at 2.5 h and returned also to control values at 24 h. In the "rest of brain", cold exposure did not alter NA synthesis at the three intervals studied. These results indicate that the activation of central noradrenergic neurones by cold is only a transient response which is restricted to specific brain areas and which can be interpreted as the consequence of an initial general stress associated with cold exposure.
Acclimatization↗
Evolution in vivo of the synthesis rate of catecholamines in various peripheral organs of the rat during cold exposure.
The synthesis of catecholamines (CA) has been studied in the heart, spleen, submaxillary glands and adrenals of rats exposed to 4 degrees C for 2.5, 24 or 48 h. The synthesis rate has been estimated 30 min after an i.v. injection of 3H tyrosine (TY) by the evaluation of the ratio: 3H-CA specific activity/3H-TY specific activity. In the sub-maxillary glands, cold exposure reduced the noradrenaline (NA) synthesis by 40% at times 24 and 48 h. In the spleen, NA synthesis was multiplied by a factor 1.6 at times 2.5 and 24 h and 2.8 at time 48 h. In the heart, it was increased by a factor 1.3 after 2.5 h, 2.8 after 24 h and 5.5 after 48 h: an important fall in cardiac NA level was observed during the first 24 h of cold exposure indicating that the synthesis capability was unsufficient to compensate the cold-induced NA release. In the adrenals, adrenaline + NA synthesis was not significantly enhanced during the first 24 h of cold exposure and increased by a factor 2.4 at time 48 h. The important increases in CA synthesis which are observed during the 24-48 h interval are likely consecutive to the induction of tyrosine hydroxylase which has been reported in the rat exposed to cold.
Adrenal Medulla↗
Effect of the activation of alpha-adrenoreceptors on the synthesis and release of noradrenaline by peripheral adrenergic nerves in vivo.
The synthesis and release of noradrenaline (NA) in the heart and submaxillary glands were studied in the rat following s.c. injections of oxymetazoline (50 mug/kg) or noradrenaline (500 mug/kg). NA release was evaluated from the decline in tissular specific radioactivity after administration of 3H-NA and NA synthesis by the estimation of the amounts of 3H-NA synthesized from 3H-tyrosine (TY) or 3H-Dopa, 30 min after the injection. Oxymetazoline treatment delayed the release of NA, the NA biological half-lives rising from 12 up to 36 hours in the heart and from 5.9 up to 21 hours in sub-maxillary glands. This inhibitory effect on NA release was interpreted as the consequence of the stimulation of alpha-adrenoreceptors. Thirty minutes after its injection, oxymetazoline increased both NA endogenous levels and 3H-NA amounts formed from 3H-TY: 3H-NA specific activities were not significantly altered. NA treatment led to an acceleration of NA release in the heart (NA biological half-life decreasing from 12 to 2.2 hours) but not in sub-maxillary glands. After injection of 3H-TY, the amounts of 3H-NA found in the heart and sub-maxillary glands were strongly reduced. Similar results were observed in the heart using 3H-Dopa as a precursor. These data are interpreted as the consequence of the removal of the newly synthesized 3H-NA by exogenous NA. The results obtained with oxymetazoline point out a dissociation between the NA release which is reduced and the NA synthesis which is unaltered. This indicates that NA synthesis rate by sympathetic nerve terminals is not immediately regulated by its release intensity. These data do not support the end-product feedback inhibition hypothesis according to which tyrosine hydroxylase is regulated by the intraneuronal NA concentration.
Adrenergic Fibers↗
[Effect of cold exposure on synthesis of cerebral dopamine (author's transl)].
The synthesis of dopamine (DA) has been studied in the striatum and cortex of rats exposed to a temperature of 40C for 2.5 or 24 h. The synthesis rate has been estimated 30 mn after an i.v. injection of 3H tyrosine (TY), by the evaluation of the ratio: 3H-DA specific activity 3H-TY specific activity. Cold exposure modified DA synthesis differently in the two brain areas. In the striatum, DA synthesis was multiplied by a factor of 1.5 after 2.5 h of cold exposure and returned to normal value after 24 h. In the cortex, cold exposure did not significantly change DA synthesis (at any of the two times studied).
Animals↗
[Influence of hypo- and hyperthyroidism on the turnover rate of noradrenaline, dopamine and serotonin in various rat cerebral structures].
The effect of chronic treatment with tyroxine (T4) or propylthiouracile (PTU) on the turnover of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) has been studied in various areas of the rat brain (brain stem, hypothalamus, striatum and "rest of the brain"). The turnover of NE and DA was determined by the decay in endogenous levels after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine and the turnover of 5-HT was evaluated by the initial accumulation of endogenous 5-HT after inhibition of monoamine oxydase by pargyline. T4 treatment accelerated the release of DA from the striatum but had no significant effects on NA release in the various cerebral areas : nevertheless the NE endogenous level was significantly reduced in the brain stem. PTU treatment delayed the release of DA and NA only from the "rest of the brain". Concerning 5-HT, the only significant variation was observed in the hypothalamus of PTU-treated rats and implied increased turnover. The possible relations between the changes in cerebral monoamines turnover and the behavioural alterations which are observed in thyroid disfunction are discussed.
Animals↗