Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Injections, Intraventricular”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources
PubMed2001

Glial cell line-derived neurotrophic factor concentration dependently improves disability and motor activity in MPTP-treated common marmosets.

Glial cell line-derived neurotrophic factor (GDNF) has previously reduced motor deficits and preserved nigral dopamine neurones in rhesus monkeys with a unilateral MPTP-induced lesion of substantia nigra. We now report on the ability of GDNF to reverse motor deficits induced by parenteral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets resulting in bilateral degeneration of the nigrostriatal pathway. Prior to GDNF administration, all MPTP-treated animals showed akinesia or bradykinesia, rigidity, postural instability and tremor. Intraventricular injection of GDNF (10, 100 or 500 microg) at 9 and 13 weeks post MPTP treatment resulted in a concentration dependent improvement in locomotor activity and motor disability which became significant after administration of 100 and 500 microg of GDNF. The most prominent improvements were in alertness, checking movements, and posture. It is concluded that intraventricular GDNF administration improves bilateral Parkinsonian motor disability following MPTP treatment and this may reflect an action of GDNF on remaining nigral dopaminergic neurones.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1973

Nerve growth factor: enhanced recovery of feeding after hypothalamic damage.

A single intraventricular injection of nerve growth factor (NGF). given at the time of brain damage, facilitated the course of recovery from the lateral hypothalamic anorexic syndrome in male rats. In the second and third weeks after the trauma, NGF-treated rats ate more food, regained body weight more rapidly, and fed more vigorously in response to intraventricular administration of norepinephrine than untreated controls. After full recovery, rats that had been treated with NGF were resistant to reinstatement of the hypothalamic syndrome by 6-hydroxydopamine. NGF may facilitate behavioral recovery by promoting the development of supersensitivity to norepinephrine and possibly also by stimulating the growth of regenerating noradrenergic neurons in the brain.

Animals↗
PubMedDate not supplied

[Effect of amizil and the ACTH4-10 fragment on the ability of mice to extrapolate the direction of movement].

Mice possessing the ability to extrapolate the direction of movement (100% of correct choices) were injected i.p. with different doses of m-cholinolytic amizil 2 hours before experiment. Doses of 2-5 mg/kg reduced the percentage of correct choices, the adequate solving strategy being replaced by stereotyped unidirectional reactions or stereotyped alternating responses. Doses of 8-12 mg/kg induced "refusals" to solve extrapolation problem. When amizil treated mice were intraventricularly injected with 1 mg/kg of ACTH4-10, their extrapolation ability was restored. This compensatory action of peptide could be mediated by its influence on cholinergic as well as on other neurotransmitter systems.

Adrenocorticotropic Hormone↗
PubMed1990

Opposite alterations in cerebrospinal fluid uridine after severe cerebral ischemia or intrathecal blood injection.

1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells.

Animals↗
PubMed1976

Ventriculography with methylglucamine iocarmate (Dimer-X). Experimental and clinical study.

In an attempt to study the use and value in ventriculography of meglumine iocarmate (Dimer-X), previously accepted as a water soluble contrast medium safe for myelography, we have conducted animal experiments to compare Dimer-X with megulumine iothalamate (Conray 60) and meglumine diatrizoate (Angiografin). We also made clinical studies of Dimer-X. In the animal experiments, 1.5 ml and 2.0 ml of Dimer-X were injected into the ventricles of 7 dogs. We noted the apparent superiority of Dimer-X over Conray 60 and Angiografin as far as side effects were concerned, but there were no particular differences in the intensities of the ventriculograms obtained. Morphological studies of the ventricles and histological examinations of the ventricular walls 1 month after intraventricular injections of Dimer-X showed no abnormalities. In the clinical studies, ventriculography with 1-5 ml Dimer-X, performed on 17 cases, aged 8 months to 62 years, with diseases of the central nervous system, produced ventriculograms of good diagnostic value with no side effects, such as convulsions, apart from mild headache or vomiting in 4 instances.

Animals↗
PubMed1988

Plasma transthyretin. Tissue sites of degradation and turnover in the rat.

Transthyretin (TTR) is involved in the plasma transport of both retinol and thyroid hormones. TTR is synthesized in the liver and choroid plexus, and in small amounts in several other tissues. A study was conducted to determine the tissue sites of degradation and turnover of TTR in the rat. The study employed TTR labeled with tyramine cellobiose (TC) and the trapped ligand method. Samples of purified rat TTR were labeled either with 125I-TC or directly with 131I. A mixture of the two labeled TTRs was injected intravenously into six rats. Blood samples were collected via a venous catheter for kinetic (turnover) analysis. After 24 or 48 h, the rats were killed, and 23 different tissues/organs were assayed as possible sites of TTR degradation. Derivatization of TTR with TC did not appreciably alter TTR plasma kinetics. Plasma turnover data were best fit by a three-pool model. The mean fractional turnover of plasma TTR was 0.15/h, and of total body TTR 0.04/h. The major sites of TTR degradation were the liver (36-38% of total body TTR degradation, almost all in hepatocytes), muscle (12-15%), and skin (8-10%). Tissues that were sites of 1-8% of body TTR degradation included kidneys, adipose tissue, testes, and the gastrointestinal tract. Less than 1% of total TTR degradation occurred in the other tissues examined. A second study was conducted in which labeled TTR was injected intraventricularly into the cerebrospinal fluid in order to explore the degradation of TTR of choroid plexus origin. The kinetics of the appearance and disappearance of such labeled TTR in plasma were physiologically reasonable, with an estimated turnover of cerebrospinal fluid TTR of the order of 0.33/h. The major tissue sites of degradation of labeled TTR injected into cerebrospinal fluid and into plasma were approximately the same. No specific degradation of TTR was found in the nervous system tissues. The most active organs of TTR catabolism, per gram wet weight, were liver and kidneys. These studies demonstrate that many tissues participate in TTR turnover and degradation; the studies provide quantitative information about the tissue sites of TTR catabolism.

Animals↗
PubMed2003

Cellular lining of the sheep pineal recess studied by light-, transmission-, and scanning electron microscopy: morphologic indications for a direct secretion of melatonin from the pineal gland to the cerebrospinal fluid.

In the sheep, the pineal hormone melatonin displays nocturnal levels 20 times as high in the cerebrospinal fluid of the third ventricle as in the jugular blood. Moreover, in the pineal recess, the evagination of the third ventricle into the pineal stalk, the levels of melatonin in the cerebrospinal fluid are even higher than in the ventral part of the third ventricle. This finding suggests melatonin to be secreted directly from the pineal gland to the ventricular lumen of the pineal recess of this species. We have, therefore, studied the interface between the sheep pineal gland and the cerebrospinal fluid by light-, scanning-, and electron microscopy of the pineal recess, as well as the permeability of the interface by tracer injections into the third ventricle. First, we show that the classic ependymal lining of the third ventricle disappears in the superior part of the recess. In this area, bulging pinealocytes, displaying immunoreactivity for serotonin, directly appose the cerebrospinal fluid. This pineal-cerebrospinal fluid interface of the sheep is large compared with other species, especially rodent species. Intraventricular injections of horseradish peroxidase and fluorescein isothiocyanate showed that both these tracers could permeate from the pineal recess into the sheep pineal parenchyma. This permeation was due to the presence of gap and intermediate junctions connecting the pinealocytes apposing the ventricular lumen. Thus, our results show that endocrine cells in this specialized area of the ventricular system are in direct contact with the cerebrospinal fluid. This finding supports the physiological concept of a direct secretion of melatonin into the cerebrospinal fluid of the sheep pineal recess.

Animals↗
PubMed1975

Self-stimulation and noradrenaline: evidence that inhibition of synthesis abolishes responding only if the "reserve" pool is dispersed first.

Although noradrenaline (NA) is thought to play a critical role in electrical self-stimulation, suppression of NA synthesis by injection of the dopamine-beta-hydroxylase inhibitor, FLA-63 (Hässle) (25 mg/kg), had little or no effect on response rates. But 3 or 5 days after prior reserpinisation, FLA-63 in the same dosage suppressed or profoundly depressed self-stimulation without eliciting signs of general incapacity. Suppression of self-stimulation could be reversed by intraventricular injection of NA, indicating that the depressant effect depended specifically on NA depletion. These findings support the view that NA may play a necessary role in self-stimulation and indicate that the NA available for this purpose included intraneuronal NA in a reserpine-sensitive reserve pool.

Animals↗
PubMed1967

Temperature effects produced in dogs and monkeys by injections of monoamines and related substances into the third ventricle.

1. In dogs the effects on rectal temperature of noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT) and of the monoamine oxidase inhibitor tranylcypromine were studied following their injection into the third ventricle through a chronically implanted cannula. Tranylcypromine was given also by the intraperitoneal route.2. The hypothermic effect of the catecholamines and the hyperthermic effect of 5-HT previously demonstrated in anaesthetized dogs were obtained also in an unanaesthetized dog, but 5-HT was effective only in doses under 20 mug.3. Tranylcypromine (1 mg) injected into the third ventricle of dogs anaesthetized with pentobarbitone sodium produced shivering and a rise in temperature.4. Tranylcypromine (10 mg/kg) injected intraperitoneally caused a rise in temperature in the unanaesthetized dog. For a time shivering and panting, two effects which produce opposite change in temperature, were observed together. When injected shortly before an intraperitoneal injection of an anaesthetizing dose of pentobarbitone sodium, tranylcypromine not only prevented the fall in temperature which is normally produced by the anaesthetic but caused a greater and longer lasting rise than when given alone.5. The intraperitoneal injections of tranylcypromine produced profuse salivation, a peripheral effect which persisted after acute denervation and which was not abolished by atropine or tolazoline.6. In rhesus monkeys anaesthetized with intraperitoneal pentobarbitone sodium, noradrenaline, adrenaline, 5-HT and 5-hydroxytryptophan (5-HTP) were injected into the cannulated third ventricle. The catecholamines caused a fall in rectal temperature. No evidence was obtained that the fall resulted from a rise in hypothalamic temperature. The injections of 5-HT or of its precursor 5-HTP raised rectal temperature. Monkeys thus respond to the monoamines injected intraventricularly, in the same way as cats and dogs, and unlike rabbits, sheep, goats, oxen and rats.

Animals↗
PubMed2005

Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors.

Several groups have suggested that transplantation of marrow stromal cells (MSCs) promotes functional recovery in animal models of brain trauma. Recent studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit, as transplanted MSCs have only limited ability to replace injured central nervous system (CNS) tissue. To gain insight into the mechanisms responsible for such effects, we systematically investigated the therapeutic potential of MSCs for treatment of brain injury. Using in vitro studies, we detected the synthesis of various growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). Enzyme-linked immunosorbent assay (ELISA) demonstrated that MSCs cultured in Dulbecco's modified Eagle medium (DMEM) produced substantial amounts of NGF for at least 7 weeks, whereas the levels of BDNF, GDNF and NT-3 remained unchanged. In studies in mice, after intraventricular injection of MSCs, NGF levels were increased significantly in cerebrospinal fluid by ELISA, confirming our cell culture results. Further studies showed that treatment of traumatic brain injury with MSCs could attenuate the loss of cholinergic neuronal immunostaining in the medial septum of mice. These studies demonstrate for the first time that by increasing the brain concentration of NGF, intraventricularly transplanted MSCs might play an important role in the treatment of traumatic brain injury.

Animals↗
PubMed1982

Lysine metabolism in the human and the monkey: demonstration of pipecolic acid formation in the brain and other organs.

Metabolism of L-[U-14C]lysine was studied in the human autopsy tissues and the intact monkeys through intracerebroventricular and intravenous injections. The human tissues were more active in the metabolism of L-[14C]lysine to [14C]pipecolate than the rat tissues previously reported. This metabolism was equally active in the phosphate (pH 7) and the glycyl-glycine (pH 8.6) buffers with the brain and the kidney having higher activity than the liver. Besides [14C]pipecolate, traces of [14C]saccharopine and alpha-[14C]aminoadipate were also detected in the liver incubation. Twenty-four hr after intraventricular injection of L-[14C]lysine to the monkey, substantial labeling of pipecolate and alpha-aminoadipate was observed in the brain and spinal cord, with the kidney, liver and the plasma having much reduced levels. Radioactivity levels of these two compounds were found low in the organs and plasma of the intravenously injected monkey. The urine of both monkeys contained only traces of [14C]pipecolate, even though it contained high levels of L-[14C]lysine and alpha-[14C]aminoadipate. It was concluded that L-lysine is actively metabolized to pipecolate and alpha-aminoadipate in the human and the monkey, that this reaction is most active in the brain when L-lysine is intraventricularly administered, and that in contrast to the rat, the monkey may have an effective renal reabsorption for pipecolate which is similar to the human.

2-Aminoadipic Acid↗
PubMed1986

Effect of GABAergic treatment on resting and stress-induced adrenocortical activities in the thalamic pigeon.

Muscimol was injected (0.5 mg kg-1) intravenously to either intact or thalamic-lesioned animals through a chronic catheter. Plasma samples were obtained at 7-min intervals and exhibited a moderate and transient increase in corticosterone levels in both groups, together with some symptoms of light discomfort (e.g., ptiloerection or panting). All these signs disappeared within 45 to 60 min. Intraventricular injection of bicuculline (3.5 micrograms) provoked a corticosterone profile quite similar to a stress-induced polyphasic pattern. Acute stress (electrical footshocks for 30 sec) was applied 2 hr after drug treatment. In controls, the stress-induced adrenocortical response appeared to be markedly modified after muscimol injection. The usual polyphasic rebounding profile was replaced by a monophasic one. This effect of muscimol did not occur when bicuculline had been injected in the 3rd ventricle. Bicuculline alone did not alter the stress-induced profile. GABAergic treatment had no effect on the monophasic response of thalamic-lesioned birds.

Adrenal Cortex↗
PubMed1991

Lack of saturable transport across the blood-brain barrier in either direction for beta-amyloid1-28 (Alzheimer's disease protein).

beta-Amyloid and related peptides are components of the neurofibrillary tangles found in the brains of patients with Alzheimer's disease and have been suggested to be directly involved in the pathophysiology of that condition. It is unclear whether the amyloid deposited in the brain arises from the peripheral circulation, which would require passage across the blood-brain barrier (BBB), or whether it is produced within the brain itself. We examined the ability of beta-amyloid1-28 (beta Am), a commercially available, biologically active fragment, radioactively labeled with 125I (I-beta Am), to cross the BBB. After IV injection of I-beta Am, radioactivity entered the brain slowly, but to a greater extent than could be attributed to its being trapped in the vascular space of the brain. Entry was not inhibited by an excess of unlabeled beta Am or by pretreatment with aluminum, indicating that entry was by the nonsaturable mechanism of transmembrane diffusion. After intraventricular injection of I-beta Am, radioactivity was cleared slowly from the brain and was not affected by excess unlabeled beta Am or by pretreatment with aluminum, indicating that clearance probably occurred with reabsorption of cerebrospinal fluid. The excess beta Am did not alter the brain/blood ratio or the clearance rate of radioactively labeled albumin, indicating that under the conditions of this experiment beta Am did not have measurable effects on BBB integrity or on the rate of reabsorption of cerebrospinal fluid. High performance liquid chromatography (HPLC) showed that I-beta Am was rapidly degraded, especially by the brain, to smaller peptide fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Peptides↗
PubMed2000

Induction by synaptic zinc of heat shock protein-70 in hippocampus after kainate seizures.

Following seizures, heat shock protein (HSP)-70 is induced in various brain regions. Since zinc that can induce HSP-70 in various cell systems is enriched in certain glutamatergic terminals and translocates to postsynaptic neurons with seizures, we examined the possibility that HSP-70 induction in the epileptic brain is mediated by synaptic zinc. Adult rats were injected intraperitoneally with kainate to induce seizures. Seizures were halted 3 h after the kainate administration by the injection of phenytoin. Staining of brain sections with zinc-specific fluorescent dye TFL at 24 h after the kainate injection revealed a one-to-one correlation between dense TFL fluorescence and acidophilic neuronal degeneration in the hippocampus. Subsequent staining with anti-HSP-70 antibody, however, revealed that more numerous neurons than degenerating neurons exhibited HSP-70 immunoreactivity. Most of the HSP-70(+) neurons were not stained with acid fuchsin but exhibited mild zinc fluorescence in the cytoplasm. Intraventricular injection of CaEDTA attenuated neuronal death as well as the HSP-70 induction in a dose-dependent manner. Supporting the specificity of zinc rather than calcium as the inducer of HSP-70 in neurons, exposure to zinc but not to a calcium ionophore or excitotoxins increased expression of HSP-70 mRNA and protein in cultured cortical neurons. The present results suggest that not only selective neuronal death, but also HSP-70 induction in neurons after seizures, is mediated by the translocation of endogenous synaptic zinc.

Animals↗
PubMed1984

On the neurotoxicity of chlordecone: a role for gamma-aminobutyric acid and serotonin.

Rats receiving the chlorinated insecticide, chlordecone (80 mg/kg i.p.), exhibit hyperexcitability, exaggerated startle response and tremors within a few hours after the injection. Since the chlordecone-elicited tremors are relieved by injections of muscarinic receptor blockers, acetylcholine has been implicated indirectly in the mechanism of chlordecone toxicity. Our studies on acetylcholine steady-state levels and turnover in several brain structures failed to detect evidence for an involvement of cholinergic presynaptic mechanisms in the chlordecone toxicity. We then investigated whether GABA is involved by measuring the rate of its accumulation following intraventricular injection of gabaculine. Chlordecone reduced the rate of GABA accumulation in striatum, but not in cerebellum, brainstem or hippocampus. Such inhibition appeared 4 h after drug injection thereby preceding the onset of tremors. Since tremors elicited by chlordecone are attenuated by the administration of serotonin receptor blockers and since chlordecone increases serotonin (5-HT) turnover, we studied whether 5-HT recognition sites are modified following chlordecone administration. We have found a reduction of the Bmax of 5-HT1 receptors in striatum and hippocampus without any modification in the kinetic characteristics of 5-HT2 receptors. We have also shown that the temporal relationship between down regulation of 5-HT1 recognition sites, reduction of striatal GABA turnover and tremors caused by chlordecone allows one to consider these 3 phenomena as reciprocally dependent. In conclusion our results favor the possibility that tremors may result from a decrease in the striatal GABergic tone which probably is elicited by an increase of serotonergic activity caused by chlordecone by a yet unknown mechanism.

Acetylcholine↗
PubMed1982

Down-regulation of beta-adrenergic receptors following repeated injections of desmethylimipramine: permissive role of serotonergic axons.

The injection of desmethylimipramine (DMI) twice daily for 3 weeks reduced the density of beta-adrenergic receptor recognition sites located in crude synaptic membranes prepared from the cortex and hippocampus and attenuated the stimulation of the membrane-bound adenylate cyclase by isoproterenol. Both actions were abolished if prior to treatment with desmethylimipramine the serotonergic axons were destroyed by an intraventricular injection of 5,7-dihydroxytryptamine. These results show that the down-regulation of beta-adrenergic receptors elicited by repeated injections of desmethylimipramine occurs only if the serotonergic axons are intact.

5,7-Dihydroxytryptamine↗
PubMed1978

Effect of central nervous system-acting drugs after selective destruction by neurotoxins of 5-hydroxytryptamine fibers in the brain.

Some behavioral effects of CNS-acting drugs have been studied in two animal species after functional impairment of central serotonergic activity. In rabbits, pretreatment with p-CPA or with 5,6-DHT counteracted the hyperthermia induced by d-amphetamine or apomorphine; the same pretreatments were ineffective in modifying pyrogen-induced fever. These data indicate a modulatory role of the 5-HT system in the hyperthermic response to dopaminergic agonists, such as d-amphetamine and apomorphine, and rule out 5-HT involvement in the hyperpyrexia induced by pyrogen. A previous intraventricular injection of 5,6-DHT significantly potentiated the increase in body temperature induced by 5-HTP in combination with a MAO inhibitor. Pretreatment with p-CPA, instead, strongly inhibited the hyperthermic response to 5-HTP. In unanesthetized fowl, at the time of the most dramatic degenerative signs of indoleaminergic neurons induced by 5,6-DHT, as documented by histofluorescence pictures, intraventricular infusion of 5-HT induced more intense behavioral, electrocortical, and body temperature modifications than in control animals. These results suggest the existence of receptor supersensitivity after 5-HT nerve ending degeneration but not after brain 5-HT depletion. The hyperthermic effect of a presynaptically acting drug, fenfluramine, was counteracted in rabbits and in fowl pretreated with either p-CPA or 5,6-DHT. Since identical behavioral, electrocortical, and body temperature effects have been observed after 5-HT or 5,6-DHT infusion into the third ventricle of fowl, it may be concluded that 5,6-DHT behaves also as a central 5-HT receptor agonist.

5-Hydroxytryptophan↗
PubMed1978

Effects of morphine and two enzyme resistant enkephalins on schedule-controlled responding in the rat.

Water-deprived rats to respond for access to a water-filled dipper under a 20 response fixed-ratio schedule. After training, the rats were each implanted with a lateral ventricle cannula and the effects of intraventricular injection of morphine, (N-methyl-tyrosyl)1-des COOH-Norleucyl5-Enkephalin, and (D-Ala)2 -(des COOH-Norleucyl)5-Enkephalin were determined. All three compounds produced dose-related decreases in FR20 responding. Morphine was about 5 times more potent than either of the two peptides. Naloxone (1.0 mg/kg, SC) antagonized the response-rate decreasing effects of intraventricular morphine and the two opiate peptides.

Animals↗