Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of adenosine on intraparenchymal cerebral blood flow was examined in conscious rabbits with the 133Xe clearance technique. Perivascular application of 10(-3) and 10(-4) M adenosine to hypothalamic blood vessels increased hypothalamic blood flow by approximately 50% (p less than 0.005). This vasodilatation was attenuated by the intrahypothalamic injection of the beta-adrenergic receptor antagonist propranolol, but was unaffected by alpha-adrenoreceptor blockade with phenoxybenzamine, or depression of neuronal activity with barbiturate. 2-Chloroadenosine, a stable analogue of adenosine, also increased hypothalamic blood flow by 50% (p less than 0.005), but this dilatation was unaffected by propranolol. These results suggest that adenosine increased hypothalamic blood flow at high concentrations by vascular receptor systems dependent on adenosine receptors and adrenergic receptors. Adenosine (10(-6) M) reduced hypothalamic blood flow by approximately 25% (p less than 0.005). This vasoconstriction was unaffected by adrenergic blockade with propranolol or phenoxybenzamine, or by inhibition of neuronal activity with barbiturate. The results suggest that adenosine decreases hypothalamic blood flow at low concentrations by stimulation of adenosine receptors associated with vascular smooth muscle.
J Cereb Blood Flow Metab 1983 Dec
PMID:Adenosine causes dilatation and constriction of hypothalamic blood vessels. 663 Mar 23

A drug surveillance study has been carried out with oral cytidine diphosphate choline (CDP-choline, citicoline, Somazina) in 2817 patients of all ages, predominating those between 60 and 80 years old. They were suffering from several neurological processes, mainly the vasculocerebral insufficiency and senile involution. Treatment was carried out for between 15 days and 2 months, the mean dose being 6 ml/d. The efficacy of the treatment was determined on the basis of the disappearance, improvement or worsening of clinical manifestations, most frequently shown by patients. The most benefited clinical manifestations by the treatment were: dizziness disappearing in 48.4% of the cases, and improving in 25.2%, cephalea disappearing in 46.5% and improving in 26.7%, insomnia with 38.6% and 24.9%, respectively; depression with 36.9% and 24.1% and memory shortage with 21.2% and 44.7% respectively. The best results were obtained in chronic cerebrovascular insufficiency, the improvements obtained in dizziness, cephalea, insomnia, fatigue and speech troubles being the most important. The safety of the drug was excellent since side effects were observed only in 5.01% of the patients. Among these effects, the most frequently seen were digestive troubles, observed in 3.6% of the cases.
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PMID:Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. 668 70

We have examined the extracellular pH (pHe) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H+ liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial PCO2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ve). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ve, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ve. A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ve, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na+/H+ counter transport (amiloride), and Cl-/HCO-3 countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.
J Cereb Blood Flow Metab 1984 Mar
PMID:Extracellular pH changes during spreading depression and cerebral ischemia: mechanisms of brain pH regulation. 669 12

The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at approximately 13 mM, was associated with a fall in Cae. Ke peaked at 48 +/- 12 mM, and Cae at 0.18 +/- 0.28 mM. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity , but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.
J Cereb Blood Flow Metab 1984 Jun
PMID:Cerebral extracellular calcium activity in severe hypoglycemia: relation to extracellular potassium and energy state. 672 31

1. A double-blind study of the effect of CDP-choline on memory impairment following bilateral ECT was performed on 22 inpatients suffering from endogenous depression. 2. Memory scores were checked after 2 and 4 ECT sessions, and the length of the post-ECT confusional state was also measured. 3. The results show no statistically significant differences between the reduced memory scores obtained by both groups. Our findings do not support the hypothesis that CDP-choline affords protection against ECT-induced memory dysfunction in depression cases.
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PMID:The value of cytidine-5-diphosphate-choline in the prevention of impairment of memory function after electric convulsive therapy. A double-blind study. 675 60

Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the oxygen-15 steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO2), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO2 and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.
J Cereb Blood Flow Metab 1982 Sep
PMID:Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction. 698 Feb 24

CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine (L-NNA) or N-nitro-L-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO.
J Cereb Blood Flow Metab 1994 Nov
PMID:Cerebral blood flow changes during cortical spreading depression are not altered by inhibition of nitric oxide synthesis. 752 32

Cortical spreading depression (CSD) was induced in male Wistar rats by applying 2 M KCl to the frontal cortex of one hemisphere for 2 h. Saline was applied to the contralateral cortex in the same manner. Following recovery for 24 h, bilateral forebrain ischemia was induced for 6 min, and the animals were permitted to survive for 6 days for assessment of histopathology. The number of necrotic neurons was counted in the cerebral cortex, striatum, and hippocampus of both hemispheres. In separate sets of animals, the effects of KCl application on cortical direct current (DC) potential and regional expression of c-fos mRNA and 72-kDa heat shock protein (hsp72) mRNA were determined. Forebrain ischemia induced selective neuronal necrosis in both hemispheres, but the number of necrotic neurons in the cerebral cortex ipsilateral to the application of KCl was significantly smaller than that in the contralateral cortex (p < 0.02, Wilcoxon signed rank test, n = 7). In the striatum and hippocampus, there were no significant differences in neuronal necrosis between hemispheres. Application of KCl for 2 h induced 11 +/- 2 (mean +/- SD, n = 5) negative deflections of DC potential in the ipsilateral cortex; none were detected in the contralateral cortex. Widespread expression of c-fos mRNA was evident in the ipsilateral cortex, while hsp72 mRNA expression was restricted to the KCl application site. The present results demonstrate that CSD induces tolerance of cortical neurons to ischemia by mechanisms unrelated to hsp72.
J Cereb Blood Flow Metab 1995 Sep
PMID:Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. 767 67

The Saccharomyces cerevisiae protein SEC14p is required for Golgi function and cell viability in vivo. This requirement is obviated by mutations that specifically inactivate the CDP-choline pathway for phosphatidylcholine biosynthesis. The biochemical basis for the in vivo relationship between SEC14p function and the CDP-choline pathway has remained obscure. We now report that SEC14p effects an in vivo depression of CDP-choline pathway activity by inhibiting choline-phosphate cytidylyltransferase (CCTase; EC 2.7.7.15), the rate-determining enzyme of the CDP-choline pathway. Moreover, this SEC14p-mediated inhibition of CCTase was recapitulated in vitro and was saturable. Finally, whereas the SEC14p-dependent inhibition of CCTase in vitro was markedly reduced under assay conditions that were expected to increase levels of phosphatidylinositol-bound SEC14p, assay conditions expected to increase levels of phosphatidylcholine-bound SEC14p resulted in significant potentiation of CCTase inhibition. The collective data suggest that the phosphatidylcholine-bound form of SEC14p effects an essential repression of CDP-choline pathway activity in Golgi membranes by inhibiting CCTase and that the phospholipid-binding/exchange activity of SEC14p represents a mechanism by which the regulatory activity of SEC14p is itself controlled.
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PMID:The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity. 781 98

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia.
J Cereb Blood Flow Metab 1995 Mar
PMID:Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain. 786 Jun 51


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