PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Infusions, Intraventricular”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 325 records · Page 18Linked to original sources
PubMed1989

Anomalous accumulation of tau and ubiquitin immunoreactivities in rat brain caused by protease inhibition and by normal aging: a clue to PHF pathogenesis?

Rats received intraventricular infusion of leupeptin or saline and brain sections were immunostained with antibodies to tau (anti-HFoPHF) or ubiquitin. Results were compared with immunostaining on normal aged rat brains and Alzheimer's disease (AD) brains. Both antibodies stained Purkinje cell perikarya and dendrites of leupeptin (but not saline)-treated and aged rat brains, as well as senile plaque neurites and neurofibrillary tangles in AD brains. The results are consistent with the hypothesis that paired helical filament (PHF) formation involves defective protein degradation.

Aging↗
PubMed1990

AF64A depletes hippocampal high-affinity choline uptake but does not alter the density of alpha-bungarotoxin binding sites or modify the effect of exogenous choline.

Sodium-dependent, high-affinity choline uptake (HACU) and the density of alpha-bungarotoxin (BuTX) receptor-binding sites were measured in the hippocampus following the intraventricular infusion of ethylcholine aziridinium ion (AF64A), a neurotoxin that competes with choline at high-affinity choline transport sites and may result in the degeneration of cholinergic axons. Eight days after the infusion of AF64A into the lateral ventricles (2.5 nmol/side), HACU was depleted by 60% in the hippocampus of experimental animals in comparison with controls, but the density of BuTX-binding sites was not altered. The administration of 15 mg/ml of choline chloride in the drinking water increased the density of BuTX-binding sites, as previously reported by this laboratory. The administration of AF64A did not prevent the effect of exogenous choline on the density of binding sites, nor did choline treatment alter the effect of AF64A on HACU. These data indicate that the density of BuTX-binding sites in the hippocampus is not altered following a substantial decrease in HACU and presumed degeneration of cholinergic axons. Since the effect of exogenous choline was not prevented by AF64A treatment, the data are interpreted to support the hypothesis that the increase in the density of BuTX-binding sites following dietary choline supplementation is attributable to a direct effect of choline on receptor sites.

Animals↗
PubMed1991

Dose-dependent responses to nerve growth factor by adult rat cholinergic medial septum and neostriatum neurons.

This study describes the relationship between the concentration of intraventricularly infused nerve growth factor (NGF) and several responses by axotomized cholinergic medial septum neurons and normal cholinergic neostriatal neurons of the adult rat. NGF infused for 14 days starting either immediately after a unilateral fimbria-fornix transection or after a 2-week delay period elicited similar dose-response relationships for the maintenance or restoration of ChAT and NGF receptor positivity and cell body size and for intraseptal 'sprouting' of the axotomized medial septum neurons. Thus, in the medial septum it appears that the expression of 'marker' molecules, cell body size and the induction of 'sprouting' are regulated by virtually the same concentrations of NGF in the two treatment strategies. This suggests that NGF has a general regulatory role and injured but untreated neurons remain fully susceptible to NGF at least up to 2 weeks after the lesion. A 14-day infusion with NGF also induced an above-normal cell body size (hypertrophy) both in axotomized medial septum and in intact striatal cholinergic neurons. The hypertrophic response of normal striatal neurons required less NGF than did that of medial septum neurons. Since the striatal response began to be detectable at a similar concentration as that required for the full maintenance or restoration of ChAT and NGF receptor positivity it could be seen as an unwanted side-effect. The definition of a sub-optimal dose with which a significant, but not maximal response can be elicited will allow future evaluations of potentially additive or synergistic actions by other agents.

Animals↗
PubMed1993

Brain-derived neurotrophic factor enhances function rather than survival of intrastriatal dopamine cell-rich grafts.

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of dopaminergic neurons from the substantia nigra in cell culture. In order to assess whether a similar survival-promoting effect is present also in vivo, we grafted fetal nigral tissue to the dopamine-depleted striatum of 6-hydroxydopamine-lesioned rats receiving two-week intraventricular infusions or daily intrastriatal injections of BDNF, NGF, or vehicle. When infused chronically at a high dose (12 micrograms/day) into the lateral ventricle, BDNF caused a behavioral syndrome of reduced food and water intake, body weight loss, and locomotor hyperactivity in comparison to NGF- and vehicle-infused graft recipients. NGF-infused graft recipients displayed a transient weight loss during the first week of infusion. At 15 days, amphetamine-induced turning was significantly attenuated to 3% of pregraft values in BDNF-infused recipients, whereas functional graft effects were not present in NGF- or vehicle-infused animals. Survival of tyrosine hydroxylase-immunoreactive graft cells, however, was similar in all treatment groups. Notably, NGF- and BDNF-infusions led to a significant size increase of cholinergic host neurons in the medial septal nucleus and the vertical limb of the diagonal band ipsilateral to the infusion, whereas there was no cholinergic neuron hypertrophy in vehicle-infused animals. Daily intrastriatal injections of BDNF (2 micrograms) produced no weight loss or locomotor hyperactivity, but also enhanced functional graft effects in BDNF-injected, as compared to vehicle-injected animals. Survival rates of grafted tyrosine hydroxylase-immunoreactive cells were, however, similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1993

Serotonergic lesions decrease mu- and delta-opiate receptor binding in discrete areas of the hypothalamus and in the midbrain central gray.

Serotonergic nerve terminals in the brain were lesioned by intraventricular infusion of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and levels of mu- and delta-opiate binding were measured in brain areas implicated in reproductive behavior and gonadotropin secretion. The lesion decreased mu-receptor binding in the preoptic area (mPOA) and the midbrain central gray, while delta-receptor binding was decreased in the mPOA and the dorsomedial nucleus of the hypothalamus. Hypothalamic serotonergic lesions also attenuated morphine inhibition of female sexual behavior. These results indicate the existence of serotonergic-opiate interactions in select regions of the brain and suggest that these interactions may be important in the regulation of lordosis behavior.

Animals↗
PubMed1995

Difference in LTP at basal and apical dendrites of CA1 pyramidal neurons in urethane-anesthetized rats.

In urethane-anesthetized rats, excitatory currents in hippocampal CA1 area following local stimulation were analyzed using the current source density technique. Systematic variation of stimulus depth revealed two dominant patterns of activation: basal versus apical dendritic excitation. The basal dendritic excitation (sink) was maximal after stimulation of stratum oriens; its onset latency was consistent with a monosynaptic excitation, and a late (presumed di- and polysynaptic) sink at the apical dendrites was observed. The apical dendritic excitation (sink) was maximal after stimulation of stratum radiatum; the early latency, presumed monosynaptic excitation was followed by a late, weak basal dendritic sink. Theta-frequency primed bursts of either high (400 microA) or low intensity (40-70 microA; 2 x threshold intensity) was delivered to either stratum oriens or radiatum, and long-term potentiation (LTP) was assessed. LTP was observed in both positive and negative components of the dipole field, as well as the (active) sink and (passive) source. Tetanus of stratum oriens resulted in a significant (P < 0.05) potentiation of the monosynaptic basal sink (at 2 ms from onset) following either high (135 + 11%, means +/- S.E.M., n = 7) or low intensity tetanus (178 +/- 21%, n = 7). Tetanus of stratum radiatum resulted in significant potentiation of the rise of the apical sink only for a high (173 +/- 51%, n = 6), but not for a low intensity tetanus (106 +/- 28%, n = 6). Significant LTP of the late apical sink was found following a high intensity tetanus of stratum oriens (155 +/- 15%, n = 7), but no significant change of the late basal sink was found following tetanization of stratum radiatum (118 +/- 20%, n = 6). UP of either the apical and basal sinks was blocked by intraventricular infusion of +/- 2-amino-5-phosphonovalerate, an N-methyl-D-aspartate antagonist. Thus, UP has a lower threshold at the basal than apical synapses of CA1 cells.

2-Amino-5-phosphonovalerate↗
PubMed1984

Presence of a paradoxical sleep (PS) factor in the cerebrospinal fluid of PS-deprived rats.

The lack of paradoxical sleep (PS) observed in rats after pharmacological blockade of the noradrenergic beta-receptors was reversed by intraventricular infusion of cerebrospinal fluid (CSF) from PS-deprived donor rats. The PS restoration in recipient animals was proportional to the duration of the deprivation in donors. It is concluded that some PS-inducing factor progressively accumulates in the CSF during deprivation. This factor acts beyond the noradrenergic step in the regulation of PS.

Animals↗
PubMed1989

Spatial learning in rats: correlation with cortical choline acetyltransferase and improvement with NGF following NBM damage.

Rats display an acquisition deficit in a circular water maze following excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Experiments were therefore performed to determine if acquisition behavior on this task could predict the degree of cortical cholinergic deafferentation and if the acquisition deficit could be pharmacologically reversed. Performance on acquisition was highly correlated with the lesion-induced reduction in cortical choline acetyltransferase (ChAT) activity. Accuracy of spatial behavior was highly correlated to percentage ChAT depletion (r = 0.75). Neither lesioned rats nor controls displayed a retention deficit after a 9-day interval, nor did either group display a passive-avoidance retention deficit. To test the causal relationship between cholinergic dysfunction and spatial behavior, the central nervous system cholinergic enhancer nerve growth factor (NGF) was intraventricularly infused for 4 weeks. NGF infusion resulted in improved acquisition of the water maze task compared to NBM-lesioned rats receiving vehicle infusion and untreated rats with NBM lesions. These studies indicate that the decrease in cortical ChAT activity is likely to be responsible for the observed acquisition deficit and that pharmacological manipulations can be successfully used to improve behavior following NBM lesions.

Animals↗
PubMed1989

Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents.

Androgens have been found to inhibit lordosis activated by estrogen treatment of ovariectomized female rats. In the present experiments, dihydrotestosterone propionate (200 micrograms for 3 days) inhibited the incidence of lordosis in ovariectomized females treated with estradiol benzoate (1 microgram for 3 days). This inhibition of lordosis was reversed 15 min after bilateral intraventricular infusion of physostigmine (10 micrograms/cannula), an acetylcholinesterase inhibitor, or carbachol (0.5 microgram/cannula), a cholinergic receptor agonist. This reversal of inhibition appears to be mediated by cholinergic muscarinic receptors since pretreatment with scopolamine (4 mg/kg, ip), a muscarinic receptor blocker, prevented the reversal of androgen inhibition by physostigmine. These results indicate that androgens may inhibit estrogen-activated lordosis through interference with central cholinergic muscarinic mechanisms.

Animals↗
PubMed1984

Beta-endorphin suppression of lordosis behavior in female rats; lack of effect of peripherally-administered naloxone.

Endogenous opioid peptides have been implicated in the control of copulatory behavior of the male rat. In order to assess the possible role of opioids in modulation of sexual receptivity in the female rat, lordosis behavior of ovariectomized (OVX) steroid-primed rats was tested after administration of beta-endorphin (B-END) or naloxone (NAL). Lordosis-to-mount ratio (L/M) of estrogen (E) - and progesterone (P) -primed rats was suppressed 15 and 45 minutes after intraventricular infusion of 100 ng B-END. This suppressive effect was blocked by subcutaneous injections of NAL (2 mg/kg). NAL alone, however, failed to enhance L/M in E-primed rats when administered in subcutaneous doses of 2 or 40 mg/kg. Thus, B-END is capable of suppressing lordotic responsiveness, but endogenous B-END does not appear to tonically suppress responsiveness in the E-primed rat.

Animals↗
PubMed1994

Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease.

Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. The highest ganglioside concentration of any organ is found in the mammalian brain, where the gangliosides are enriched in the neuronal membrane, particularly in the synapses. There are four major brain gangliosides with the same neutral tetrasaccharide core to which one to three sialic acids are linked--the simplest being the GM1-ganglioside. These gangliosides have been shown to have neuritogenic and neuronotrophic activity and to facilitate repair of neuronal tissue after mechanical, biochemical or toxic injuries. Mixtures of native bovine brain gangliosides were adopted for pharmacological use in the treatment of peripheral nerve damage, and GM1-ganglioside has been applied for the treatment of CNS injuries and diseases. Beneficial effects of GM1 have been documented in the treatment of stroke and spinal cord injuries, particularly when the treatment has been initiated within a few hours of the acute event. Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).

Alzheimer Disease↗
PubMed1980

Muscarinic receptor binding and behavioral effects of atropoine following chronic catecholamine depletion or acetylcholinesterase inhibition in rats.

Rats were subjected to one of two experimental treatments: (1) intraventricular infusion of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA), known to permanently reduce brain dopamine and norepinephrine levels, or (2) chronic administration of the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP). Both treatments are believed to produce relative overactivity of cholinergic systems and to suppress forward locomotion. The anticholinergic agent atropine sulfate yielded excessive forward walking in otherwise chronically akinetic 6-OHDA-treated rats, whereas atropoine slightly decreased locomotion in controls. The hypothesis that such supersensitivity to atropine may be related to a reduction in the density of muscarinic cholinergic receptors was not supported: First, 3H-quinuclidinyl benzilate (QNB) binding to membrane preparations was not decreased in the 6-OHDA-treated rats; secondly, atropine did not induce excessive forward locomotion in the DFP-treated rats in which 3H-QNB binding was decreased. There were other changes in the DFP-treated rats consistent with muscarinic receptor alteration, including tolerance to the locomotor suppressive effects of DFP, cross tolerance to the cholinergic agonist pilocarpine, and exaggerated atropine-induced increases in core temperature and stereotypy. It is concluded that 6-OHDA and DFP produce different long-term changes in cholinergic brain systems and atropine-sensitive behaviors.

Animals↗
PubMed1987

Harman induces preference for ethanol in rats: is the effect specific for ethanol?

Increasing concentrations of either ethanol, etonitazene, clomethiazole or midazolam were offered to male Wistar rats for 21 days. Between day 8 and day 21, the animals were treated with several doses of harman, harmalan, and tetrahydronorharman (tetrahydro-beta-carboline) by means of continuous intraventricular infusion. Harman and THN induced a significant preference for ethanol in a dose-dependent manner. Harman was approximately three times more potent than THN. The amount of ethanol consumed during the second and third weeks of the experimental period correlated with the harman concentration in the brain after the cessation of the treatment (p less than 0.01). Harman infusion attenuated the clomethiazole intake, whereas that of etonitazene and midazolam was not affected as compared with CSF-treated rats. By counting licking movements, it was found that the rats drank ethanol and water at distinct time periods with the pattern dependent on the concentration of the ethanol solution offered. The intervals between the maxima were 6 to 8 hours at low ethanol concentrations. Relatively high concentrations caused a disruption of the regular rhythms in favour of shorter ones with increasing intervals between the maxima (3 hr, 4 hr, 5 hr intervals). Harman treatment (27 nmol/hr) disturbed the regular rhythms at lower ethanol concentrations but mimicked the ultradian rhythm which was observed at high ethanol concentrations in CSF-treated animals. The observed coincidence of water and ethanol intake was uncoupled if the highest ethanol concentration in both treatments was offered. Thus, treatment with harman changed the rhythm of fluid intake in a direction which was detected in CSF-treated rats only at relatively high ethanol concentrations.

Activity Cycles↗
PubMed1985

A method for microscopic studies of cerebral angioarchitecture and vascular-parenchymal relationships, based on the demonstration of 'paravascular' fluid pathways in the mammalian central nervous system.

A new method is described for morphological studies of blood vessels and related cellular elements in the mammalian central nervous system (CNS). The tracer protein, horseradish peroxidase (HRP), in solution, is infused intraventricularly or intracisternally in anesthetized animals over 5-10 min. During this period, HRP in the subarachnoid space enters the perivascular spaces around penetrating arterioles and rapidly permeates the gliovascular basal laminae surrounding capillaries. After fixation by intravascular perfusion of aldehydes, brain sections are incubated with the highly sensitive chromogen, tetramethylbenzidine. Intraparenchymal blood vessels throughout the CNS are vividly demonstrated for light microscopy by HRP reaction product in their perivascular spaces or basal laminae. Correlative ultrastructural investigations of specific blood vessels and related parenchymal elements can be conducted using adjacent sections.

Animals↗
PubMedDate not supplied

Ciliary neurotrophic factor (CNTF) promotes low-affinity nerve growth factor receptor and CD4 expression by rat CNS microglia.

Ramified parenchymal microglia may provide immune surveillance in the nervous system and become activated in response to injury, showing increases in antigens found on macrophages, e.g. CD4 and MHCs. We investigated in adult rats the effects of a 2-week intraventricular infusion with ciliary neurotrophic factor (CNTF), a nervous system-associated cytokine, on microglia of the normal and injured corpus callosum. CNTF caused morphological changes, induced the expression of low-affinity nerve growth factor receptor and CD4 and increased the expression of complement receptor 3. Such changes were also observed after treatment of pure cultures of neonatal rat microglial cells with highly purified CNTF, suggesting a direct responsiveness to CNTF. Thus, endogenous astroglial and Schwann cell-derived CNTF may be an important component of the immune responses of the nervous system.

Animals↗
PubMed1991

Differential regulation of estrogen-dependent sexual development of rat brain by growth factors.

Intraventricular infusion of antiserum to nerve growth factor (ANGF), but not that to insulin, epidermal growth factor nor normal rabbit serum, resisted estrogen-induced behavioral defeminization in the female rat neonates. A significant number of the ANGF-treated rats showed lordosis as adults despite neonatal estrogen, but positive feedback of estrogen on serum luteinizing hormone was absent. Sexual phenotype in behavioral and gonadotropic functions may be under differential development regulation.

Animals↗
PubMed1990

Theories on the promotion of CNS transplant integration by selective activation of presynaptic enzyme cascades: prospects for future clinical applications.

It is hypothesized that multiple parallel presynaptic enzyme cascades act concertedly to regulate synaptic plasticity. These enzyme cascades include phospholipases A2 and C, protein kinase C, calcium/calmodulin and cAMP-dependent protein kinases and adenylate cyclase. New putative neurotrophic agents are postulated based on their ability to activate these enzymes. The artificial induction and amplification of multiple presynaptic enzymes in the fetal graft-mature host CNS tissue complex should maximally augment axon growth and synaptogenesis. In turn this would lead to enhanced transplant integration and hence maximal functional neurologic restoration. These enzyme cascades could be stimulated in-vivo by the intraventricular infusion of receptor-specific and/or lipophilic neurotrophic agents as well as by the application of external electric fields. A theoretical construct is formulated for developing future grafting experimentation with the hope of ultimately applying these concepts to the amelioration of human neurodegenerative diseases.

Animals↗