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At least 883 records · Page 49Linked to original sources
PubMed1999

Diffusion barriers evoked in the rat cortex by reactive astrogliosis.

Changes in extracellular space (ECS) diffusion parameters in astrogliotic tissue around a unilateral cortical stab wound were determined from concentration-time profiles of tetramethylammonium (TMA(+)) using TMA(+)-selective microelectrodes. Three diffusion parameters-ECS volume fraction alpha (alpha = ECS volume/ total tissue volume), tortuosity lambda (lambda(2) = D/ADC; where D is the free and ADC is the apparent diffusion coefficient of TMA(+) in the brain), and nonspecific TMA(+)uptake k'-were determined at 3, 7, 21, and 35 days postwounding (dpw), in the hemispheres ipsilateral and contralateral to the lesion. Following diffusion experiments, tissue sections were immunostained for glial fibrillary acidic protein (GFAP) and chondroitin-sulphate proteoglycans (CSPG). In the area 300-1000 micron around the wound, alpha was increased at 3, 7, and 21 dpw by about 20% but returned to control values at 35 dpw; lambda was increased at all four intervals, reaching a maximum at 7 dpw. k' was lower than in the contralateral hemisphere at 7, 21, and 35 dpw. Measurements 1,500-2,000 micron from the wound revealed only an increase in lambda at 7 dpw. The time course of changes in ECS diffusion parameters closely correlated with increased staining for GFAP and CSPG. Our results show that astrogliosis significantly changes the diffusion properties of nervous tissue, making it less permissive. Both hypertrophied astrocytic processes and an enhanced formation of some extracellular matrix molecules could affect, through changes in the diffusion of molecules in the ECS, neuron-glia communication, "cross-talk" between synapses, extrasynaptic transmission, and regenerative processes.

Algorithms↗
PubMed2000

Nicotine-induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid.

The present electrophysiological study shows that manipulation with endogenous brain kynurenic acid (KYNA) is able to affect the response of central noradrenergic neurons to nicotine. Previous studies have shown that systemically administered nicotine in low doses is associated with a marked, but short-lasting increase in the firing rate of rat noradrenergic neurons in the locus coeruleus (LC). This action of nicotine is of peripheral origin and finally mediated via a release of glutamate within the LC. KYNA is an endogenous glutamate receptor antagonist, which shows an uneven distribution in human brain. Previous studies have shown that a potent inhibitor of kynurenine 3-hydroxylase, PNU 156561A, is able to dose-dependently increase the levels of KYNA in brain. Anesthetized rats were given PNU 156561A in a dose that caused a 5-fold increase in brain KYNA levels after 3-6 hours (40 mg/kg, i.v. ). This treatment was found to abolish the increase in firing rate of LC neurons induced by nicotine (25-200 microg/kg, i.v.). The results of the present study show that an increased concentration of endogenous brain KYNA is able to inhibit the activation of central noradrenergic neurons by nicotine. In addition, our results highlight the role of endogenous KYNA in brain as a potentially important modulator of brain glutamatergic responses.

Animals↗
PubMed1990

Modulation of nicotine receptors by chronic exposure to nicotinic agonists and antagonists.

Although numerous studies have demonstrated that chronic nicotine treatment often results in tolerance to this drug, the mechanisms that underlie this tolerance are not well defined. Recent evidence suggests that chronic nicotine treatment results in an up-regulation of brain nicotinic receptors, but the majority of these receptors may be desensitized or inactivated, thereby explaining tolerance. There is evidence that while all mouse strains show increased receptor numbers following chronic nicotine treatment, some mouse strains develop maximal changes in [3H] nicotine binding before any tolerance is detected. Other strains show a high correlation between increase in receptor number and tolerance. Studies with several other nicotinic agonists indicate that up-regulation of nicotine receptors can occur without changes in drug sensitivity. Similarly, chronic antagonists treatment can also elicit changes in receptors without affecting sensitivity to nicotine. Some of these discrepancies may be due to genetically influenced interactions between the adrenal steroid, corticosterone (CCS), and the nicotinic receptors. The addition of CCS in vitro inhibits binding to nicotinic receptors, and chronic CCS treatment results in decreases in the number of brain nicotinic receptors measured by [125I] bungarotoxin binding. Either of these biochemical measures may explain why altering CCS concentrations in vivo results in altered sensitivity to nicotine. It may be that both changes in the number of receptors and altered steroid interactions with the nicotinic receptors explain tolerance to nicotine.

Animals↗
PubMedDate not supplied

Long-term diffusive samplers for the indoor air quality evaluation.

Three kinds of diffusion samplers, conceived to perform long-term samplings in indoor sites are illustrated in this work. Two of them, in part deriving from the previous "Analyst for VOC" device, extend the field of application up to the semi-volatile organic compounds (SVOC), PAHs and nicotine in particular. A third device, which employs a basic barium hydroxide solution as an absorbing medium, is proposed for the determination of carbon dioxide levels which indicate the air change quality in the indoor sites. Laboratory and field experiments, performed in order to assess the reliability of the proposed devices, are shown. A monthly monitoring campaign, performed at three private apartments in Rome and its outskirts highlights that the indoor pollution levels are a complex function of various concurrent and opposite factors, like external air pollution, internal sources, air change rate and sink effect of surfaces, which contribute to depletion phenomena through adsorption and/or decomposition processes.

Air Pollution, Indoor↗
PubMed2005

Nicotine-induced embryonic malformations mediated by apoptosis from increasing intracellular calcium and oxidative stress.

BACKGROUND: Tobacco smoking by women during pregnancy increases the risk of congenital birth defects in the infants. Among the smoke products, nicotine is believed to be the major teratogenic factor that perturbs embryonic development. However, the role of nicotine in embryonic malformations has not been addressed, and the mechanisms by which nicotine affects embryonic development remain to be delineated. METHODS: To investigate the effects of nicotine on early embryogenesis, murine embryos at embryonic day (E) 8.5 were dissected out of the uteri, cultured in a roller bottle system, and treated with nicotine (0.6-6 microM) or vehicle. Embryonic morphogenesis and growth were examined in terms of structural morphology and crown/rump length, respectively. Programmed cell death (apoptosis) was assessed using LysoTracker Red staining of whole mount embryos and TUNEL assay of tissue sections. Changes in intracellular calcium concentration ([Ca2+]i) and reactive oxygen species (ROS) production were assessed using fluorescent dyes (Flu-4, AM; H2DCFDA, respectively) under a confocal microscope. To further investigate the role of intracellular calcium and ROS in nicotine-induced embryopathy, embryos were treated with BAPTA-AM (2 microM) to inhibit [Ca2+]i elevation and ascorbic acid (vitamin C; 100 microg/ml) to scavenge ROS in presence of nicotine (6 microM). RESULTS: The embryos treated with nicotine in 3-6 microM were smaller than those treated with vehicle. Most of the embryos had open neural tube in the anterior (brain) regions. The embryos treated with 6 microM nicotine also exhibited severe defects in the posterior trunk, resembling caudal dysplasia. Excessive apoptosis was observed in the deformed structures. Significant increases in [Ca2+]i and ROS were seen in the tissues that had higher levels of apoptosis. Furthermore, inhibition of [Ca2+]i and scavenging of ROS significantly reduced embryonic malformation and apoptotic rates in the embryos. CONCLUSIONS: Nicotine affects embryonic development in a concentration-dependent manner. The nicotine-induced embryonic malformations are, in part, a result of excessive cell death. Nicotine increases [Ca2+]i and ROS level, which play a role in nicotine-induced embryonic apoptosis and malformations. These studies identify the molecular pathway of nicotine action in embryonic apoptosis and malformations, and provide a promising approach for ameliorating the teratogenic effects of nicotine.

Abnormalities, Drug-Induced↗
PubMed2001

Combined effects of cocaine and nicotine on cardiovascular performance in a canine model.

BACKGROUND: With the proliferation of cocaine abuse, increased incidence of catastrophic cardiovascular events such as angina pectoris, myocardial infarction, ventricular arrhythmias, or sudden death are reported. Many of these patients also smoke cigarettes before and after cocaine use, leading to a high frequency of simultaneous exposure to both drugs. Cocaine's and nicotine's independent effects on cardiodynamics are well documented, but combined effects of both on complete cardiovascular hemodynamics remain unknown. HYPOTHESIS: The study aimed to determine whether these effects are additive, synergistic, or antagonistic and was therefore designed to investigate the cardiovascular changes produced as a result of combined administration of cocaine and nicotine in a canine model. METHODS: Initially, in phase 1, 30 experiments were performed to study the dose-response curve of both drugs. In phase II and III, 12 dogs were subjected to 30 experiments. In phase II, cocaine was given intravenously (IV) followed by nicotine. In phase III, sequence of drug administration was reversed to study the effects on hemodynamics and coronary artery blood flow reserve. RESULTS: Hemodynamic parameters observed were Phase I: Dose-response curve established the IV bolus dose of cocaine 2 mg/kg and nicotine 50 microg/kg. Phase II: Cocaine increased heart rate, blood pressure, and dP/dt, but nicotine administration after cocaine produced marked significant synergistic excitatory effects: dP/dt increased from 1,810 +/- 210 to 6,300 +/- 460 (p < 0.003). Phase III: Nicotine significantly increased heart rate, mean arterial pressures, left ventricular end-diastolic pressure, pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Nicotine increased dP/dt (1,810 +/- 192 to 5,000 +/- 160 mmHg/s; p < 0.004). These excitatory effects of nicotine were attenuated by cocaine when administered as a second drug (dP/dt decreased to 1,925 +/- 144 from 5,000 +/- 160 mmHg/s;p < 0.004). CONCLUSIONS: Cocaine, when administered alone, caused increase in heart rate, blood pressure, and dP/dt, but nicotine showed a significant increase in all the hemodynamic parameters. Both drugs reduced coronary blood flow reserve. In combination, cocaine plus nicotine administration had synergistic excitatory effects in dogs. A reversed drug combination, that is, nicotine plus cocaine, attenuated the excitatory effects of nicotine.

Animals↗
PubMed2002

Diffusion parameters in the striatum of rats with 6-hydroxydopamine-induced lesions and with fetal mesencephalic grafts.

Functional recovery after transplantation of dopaminergic cells into the lesioned striatum is dependent on widespread diffusion of the transmitter released by the graft. In the present study, we investigated the diffusion parameters of the extracellular space in the striatum of control, 6-hydroxydopamine-lesioned, intrastriatally grafted, and sham-grafted rats in vivo. We used two types of grafts-single macrografts or multiple micrografts. The real-time iontophoretic tetramethylammonium method enabled us to extract three extracellular space diffusion parameters: volume fraction, alpha, tortuosity, lambda, and nonspecific uptake of tetramethylammonium, k'. Compared with controls (alpha = 0.19, lambda = 1.59), in lesioned animals both alpha and lambda were lower (alpha = 0.14, lambda = 1.50). alpha and lambda were increased inside macro-and micrografts, where alpha = 0.24 and lambda = 1.80, and in sham-grafted areas, where alpha = 0.24 and lambda = 1.72. In regions outside the grafts (alpha = 0.15, lambda = 1.51) or in sham grafts (alpha = 0.14, lambda = 1.49), the values of alpha and lambda were similar to the values observed in lesioned striatum. Nonspecific uptake (k') did not differ among the groups. Our results show that, compared with control, alpha and lambda were decreased in dopamine-depleted areas and increased in areas with grafts. Multiple but smaller graft deposits, in contrast to their enlarged capability for dopaminergic reinnervation, impair the conditions for diffusion and extrasynaptic transmission in a larger area of the striatum than do single macrografts, presumably because of more extensive tissue damage, cell loss, and astrogliosis.

Animals↗
PubMed2003

Chronic nicotine administration increases NGF-like immunoreactivity in frontoparietal cerebral cortex.

Nicotine/nicotine agonists, which have been proposed as therapeutic agents for the treatment of Alzheimer's disease and other neurodegenerative disorders, produce a wide variety of effects on the nervous system. Some mechanisms involved remain poorly understood. In this work, immunohistochemical techniques were used to determine the effect of nicotine on nerve growth factor (NGF) in the frontoparietal (motor, somatosensory) brain cortex of the albino rat. Nicotine was chronically administered intraperitoneally using osmotic pumps (0.35 mg nicotine base/kg body weight/day for 14 days). An increase in the number and the immunoreaction intensity of NGF-like positive pyramidal and nonpyramidal neurons of these cortical areas was observed after treatment. Immunopositive astroglial cells were always seen in sections of treated animals but not in controls. The neuropil of control animals was, in general, devoid of reaction, but in treated animals, immunopositive prolongations were located randomly, some in close association with capillaries. At the electron microscopic level, these prolongations were demonstrated as belonging to neurons (dendrites and axons) and astroglial cells. Nicotinic activation of selected neurons and glial cells seems to trigger NGF/neurotrophic mechanisms, suggesting their use may be of benefit in prevention and treatment of neurodegenerative diseases.

Animals↗
PubMed2002

Water ADC, extracellular space volume, and tortuosity in the rat cortex after traumatic injury.

The diffusion parameters in rat cortex were studied 3-35 days following a cortical stab wound, using diffusion-weighted MR to determine the apparent diffusion coefficient of water (ADC(W)) in the tissue, and the real-time iontophoretic tetramethylammonium (TMA) method to measure the extracellular space (ECS) diffusion parameters: ECS volume fraction alpha and the ADC of TMA(+) (ADC(TMA)). Severe astrogliosis was found close to the wound, and mild astrogliosis was found in the ipsilateral but not the contralateral cortex. Chondroitin sulfate proteoglycan (CSPG) expression was increased throughout the ipsilateral cortex. In the hemisphere contralateral to the wound, alpha, ADC(TMA), and ADC(W) were not significantly different from control values. ECS volume fraction was increased only in the vicinity of the wound, in the region of cell death and severe astrogliosis, at 3 and 7 days after injury. However, both ADC(TMA) and ADC(W) were significantly decreased after lesion in the vicinity of the wound as well as in the rest of the ipsilateral hemisphere distant from the wound. Thus, both ADC(W) and ADC(TMA) decreased in regions wherein alpha did not change but CSPG increased. An increase in extracellular matrix expression may therefore impose diffusion barriers for water as well as for TMA molecules.

Animals↗
PubMed1996

Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia.

To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac arrest using 1H MRS/MRI and 31P MRS, respectively. The time courses of the MR parameters were compared with changes in the extracellular space (ECS) volume fraction (alpha) and tortuosity (lambda), determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. The data show a decrease of the ADC of tissue water after induction of global ischemia of which the time course strongly correlates with the time course of the decrease in the ECS volume fraction and the increase in ECS tortuosity. This indicates that cell swelling is an important cause for the ADC decrease of water.

Animals↗
PubMed1991

Dual muscarinic and nicotinic action on a motor program in Drosophila.

The effect of cholinergic agonists and antagonists on the central pattern generator of the pharyngeal muscles has been studied in third instar larvae of Drosophila. The pharyngeal muscles are a group of rhythmically active fibers involved in feeding. Bath application of the cholinergic agonists carbachol, muscarine, pilocarpine, and acetylcholine (ACh) to a semiintact preparation including the pharyngeal muscles and the central nervous system (CNS), initiated long-lasting endogenous-like bursting activity in the muscles. The muscarinic antagonists, atropine and scopolamine, blocked these responses as well as endogenous activity. Perfusion with nicotine elicited a short, tonic response that was marginally blocked by mecamylamine but not by curare, alpha-bungarotoxin, hexamethonium, or the muscarinic antagonists. This is the first time that a response to cholinergic drugs has been examined in Drosophila. The pharyngeal muscle preparation may prove to be a valuable system for studying mutations of cholinergic metabolism, receptors, and second messengers.

Acetylcholine↗
PubMed1997

Dual effect of digitalis glycosides on norepinephrine release from human atrial tissue and bovine adrenal chromaffin cells: differential dependence on [Na+]i and [Ca2+]i.

It was the aim of the present study (1) to characterize the influence of Na+/K(+)-ATPase inhibition by the digitalis glycoside ouabain on both spontaneous and nicotine-evoked norepinephrine release from the human heart; and (2) to further investigate the role of glycoside-induced changes in [Na+]i and [Ca2+]i (determined by microfluorimetry) for catecholamine release. The latter experiments were performed in bovine adrenal medullary chromaffin cells (BCC), an established cell culture model for sympathetic nerves. Ouabain (1-1000 mumol/l) exerted a dual effect on norepinephrine release (determined by HPLC) from incubated human atrial tissue: (I) Ouabain induced a concentration-dependent increase in norepinephrine release, that was calcium-independent and almost completely prevented by blockade of the uptake1-carrier by desipramine (1 mumol/l). The characteristics of this release process are consistent with a non-exocytotic mechanism. (II) In addition, ouabain augmented the nicotine-evoked (1-100 mumol/l) calcium-dependent norepinephrine release, which can be considered to be exocytotic. Na+/K(+)-ATPase inhibition also reduced the threshold concentration of nicotine from 10 to 1 mumol/l and it delayed the rapid tachyphylaxis of its norepinephrine releasing effect in human atrial tissue. In BCC, ouabain increased [Na+]i, [Ca2+]i and [3H]-norepinephrine release in parallel. Under calcium-free conditions, not only the ouabain-induced increase in [Na+]i, but also [3H]-norepinephrine release were enhanced. The ouabain-induced [3H]-norepinephrine release was always closely related to changes in [Na+]i, indicating a key role of [Na+]i for this calcium-independent non-exocytotic norepinephrine release. In addition, pretreatment with ouabain (1 mmol/l) augmented the nicotine-evoked (0.1-10 mumol/l) increments in [Na+]i, [Ca2+]i and [3H]-norepinephrine release. As nicotine-induced norepinephrine release depends on an increase in both [Na+]i and [Ca2+]i, these findings are indicative of an ouabain-mediated facilitation of exocytosis. In conclusion, increasing [Na+]i and [Ca2+]i inhibition of Na+/K(+)-ATPase by ouabain triggers non-exocytotic norepinephrine release, and facilitates nicotine-evoked exocytotic norepinephrine release.

Adrenal Medulla↗