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Results for “Infusions, Intraventricular”

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PubMed1976

Influence of altered CSF solute composition on parotid salivary secretion in goats.

Infusions of hypertonic NaCl solution into the CSF of the lateral cerebral ventricle of the goat caused a marked reduction in parotid salivary flow concomitant with a rise in salivary [Na+]. Corresponding infusions of iso- or hypertonic glucose and glycerol solutions affected salivary secretion in the opposite direction. The possibility is discussed that a periventricular sodium-sensitive mechanism, which is of importance in the central control of fluid balance, also may participate in the regulation of parotid secretion in the goat. This interpretation of the results is to some extent obscured by the observation of a high incidence of intermittent rumination during the intraventricular infusions of glucose and glycerol solution.

Animals↗

PubMed1984

Effects of cerebroventricular administration of ouabain on renal hemodynamics in anesthetized dogs: evidence for the participation of renal dopaminergic vasodilator fibers.

Cerebroventricular infusion of ouabain (10(-6) M) in cerebrospinal fluid produced significant increases in renal blood flow and reductions in renal vascular resistance in chloralose anesthetized, vagotomized dogs; these renal effects were not accompanied by any changes in arterial blood pressure and heart rate. Infusion of a higher concentration of ouabain (10(-5) M) enhanced significantly blood pressure, heart rate, renal vascular resistance and reduced renal blood flow. The renal vasodilator effects precipitated by lower concentration of ouabain have not been documented before and the mechanisms involved in these observations were investigated in the present study. Pretreatment of the dogs with indomethacin did not prevent renal vasodilator effects of ouabain, indicating that prostaglandins were not involved. Acute renal denervation abolished these actions suggesting that these renal vascular effects were mediated neurogenically. In the dogs, pretreated with i.v. sulpiride, a dopamine receptor antagonist, central infusions of ouabain (10(-6) M) produced significant increases in blood pressure, renal vascular resistance and reduced renal blood flow. These effects were opposite to those noted in control animals. These data suggested that vasodilatation induced by central ouabain was mediated via activation of renal dopaminergic fibers. Prior intraventricular infusion of small doses of sulpiride that antagonized central dopamine receptors, without affecting peripheral sites, also prevented but did not reverse the renal effects of ouabain. Selective blockade of central alpha receptors with phentolamine also abolished ouabain-induced renal vasodilatation. In addition, after central alpha receptor blockade ouabain increased arterial blood pressure. In the dogs pretreated with i.v. phentolamine, cerebroventricular ouabain did not produce any changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy.

We report on the clinical outcome of a first case of intracranial infusion of nerve growth factor (NGF) to an Alzheimer patient. The therapeutic attempt is based on animal research showing that NGF stimulates central cholinergic neurons of the type known to be lost during the development of Alzheimer's disease (AD). Furthermore, our own previous clinical experience of infusing NGF to support the survival of intracranially transplanted adrenal chromaffin cells to Parkinsonian patients indicate this approach to be technically possible and safe and clinically of significant potential. Our first case was a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF over three months resulted in a marked transient increase in uptake and binding of [11C]nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF infusion, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects of the NGF infusion were found. The results of this single case indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Aged↗

PubMed1998

Co-infusion with a TrkB-Fc receptor body carrier enhances BDNF distribution in the adult rat brain.

Fusion proteins comprising the Fc domain of human IgG and extracellular domains of receptor tyrosine kinases can neutralize the activity of their cognate ligands when administered in molar excess. We have generated a fusion protein using the ectodomain of TrkB (TrkB-Fc). Although the ability of TrkB-Fc to neutralize the activity of brain-derived neurotrophic factor (BDNF) in vitro has been demonstrated, there have been no conclusive demonstrations of its ability to neutralize the activity of BDNF in vivo. We co-infused TrkB-Fc with BDNF into the cortex and hippocampus of adult rats to determine whether TrkB-Fc would interfere with the ability of BDNF to upregulate neuropeptide Y (NPY). We report here that rather than neutralizing the activity of exogenous BDNF, co-infusion with the TrkB-Fc fusion protein greatly increased the volume of tissue in which neuropeptide Y immunostaining was upregulated. In addition, TrkB-Fc greatly enhanced BDNF's distribution through adult brain parenchyma. TrkB-Fc also markedly increased the otherwise limited diffusion of BDNF into brain parenchyma following intraventricular infusion. These results show that rather than neutralizing or sequestering BDNF, the TrkB-Fc, at close to molar equivalence to BDNF, can function as a carrier for BDNF and thus enhance the delivery or penetration of this polypeptide into the brain.

Animals↗

PubMed1997

Effects of serotonin 1A or 1B receptor agonists on social aggression in male and female Syrian hamsters.

Numerous studies have demonstrated that activation of serotonin 5-HT1A or 5-HT1B receptor decreases aggression in male mammals. To determine whether female mammals also show decreased aggression in response to 5-HT1A or 5-HT1B activation, we assessed the effects of the serotonin receptor agonists 8-OH-DPAT (5-HT1A) and CGS-12066A (5-HT1B) on aggression in female Syrian hamsters. Female Syrian hamsters were tested for interfemale aggression 2 days before and 15 min after receiving intracerebroventricular infusions of 8-OH-DPAT (5, 10, 20 microg) or CGS-12066A (5, 10, 20 microg). Neither drug affected aggression as measured by the latency and frequency of attacks or uprights, although the highest dose of 8-OH-DPAT increased general activity. For male hamsters, intraventricular infusions of 10 microg of 8-OH-DPAT essentially eliminated aggression, whereas 5 microg of 8-OH-DPAT or 20 microg of CGS-12066A were without effect. Systemic treatment with 8-OH-DPAT (1 mg/kg body weight) did reduce aggression in females, although there was an attendant increase in symptoms of nonspecific serotonergic activity. There were no behavioral effects of systemic CGS-12066A (4 mg/kg body weight) on female hamsters. These results indicate that there may be sex differences in the neurochemical regulation of aggression and point to a need for more studies directed at this issue.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2003

Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats.

Nogo-A is a myelin-associated neurite outgrowth inhibitory protein limiting recovery and plasticity after central nervous system injury. In this study, a purified monoclonal anti-Nogo-A antibody (7B12) was evaluated in two rat stroke models with a time-to-treatment of 24 hours after injury. After photothrombotic cortical injury (PCI) and intraventricular infusion of a control mouse immunoglobulin G for 2 weeks, long-term contralateral forepaw function was reduced to about 55% of prelesion performance until the latest time point investigated (9 weeks). Forepaw function was significantly better in the 7B12-treated group 6 to 9 weeks after PCI, and reached about 70% of prelesion levels. Cortical infarcts were also produced in spontaneously hypertensive rats (SHR) by permanent middle cerebral artery occlusion (MCAO). In the control group, forepaw function remained between 40% and 50% of prelesion levels 4 to 12 weeks after MCAO. In contrast, 7B12-treated groups showed significant improvement between 4 and 7 weeks after MCAO from around 40% of prelesion levels at week 4 to about 60% to 70% at 7 to 12 weeks after MCAO. Treatment in both models was efficacious without influencing infarct volume or brain atrophy. Neuroanatomically in the spinal cord, a significant increase of midline crossing corticospinal fibers originating in the unlesioned sensorimotor cortex was found in 7B12-treated groups, reaching 2.3 +/- 1.5% after PCI (control group: 1.1 +/- 0.5%) and 4.5 +/- 2.2% after MCAO in SHR rats (control group: 1.8 +/- 0.8%). Behavioral outcome and the presence of midline crossing fibers in the cervical spinal cord correlated significantly, suggesting a possible contribution of the crossing fibers for forepaw function after PCI and MCAO. The results suggest that specific anti-Nogo-A antibodies bear potential as a new rehabilitative treatment approach for ischemic stroke with a prolonged time-to-treatment window.

Animals↗

PubMed1998

Secondary hemorrhage after intraventricular fibrinolysis: a cautionary note: a report of two cases.

OBJECTIVE AND IMPORTANCE: To hasten the lysis of intraventricular hemorrhages, intraventricular administration of recombinant tissue plasminogen activator (rt-PA) or urokinase has been advocated as an effective and safe treatment for patients with intraventricular hemorrhage. Until now, cases of secondary hemorrhage after intraventricular fibrinolysis, to our knowledge, have not been reported in the literature. We present a report of two patients with clinically significant bleeding complications associated with intraventricular infusion of rt-PA. CLINICAL PRESENTATION: Both patients, a 42-year-old woman (Patient 1) and a 70-year-old man (Patient 2), suffered from hypertensive left-sided thalamic hemorrhage with ventricular extension and ventricular dilatation. INTERVENTION: Both patients required external ventricular drainage and were treated with intraventricular rt-PA. In Patient 1, a secondary intraventricular hemorrhage occurred 20 minutes after the first instillation of 2 mg of rt-PA and was associated with a sudden loss of consciousness. Treatment with rt-PA was stopped, and the patient needed a permanent shunt. In Patient 2, intraventricular subsequent bleeding was noted 4 hours after the second 4-mg dose of rt-PA, clinically apparent as anisocoria. In Patient 2, rt-PA administration was continued without further complications. In both patients, a second external ventricular drainage was required after secondary hemorrhage. CONCLUSION: Intraventricular lysis is a potentially hazardous therapy. To weigh the potential benefits against the potential risks, a controlled study of this promising new treatment is urgently warranted.

Adult↗

PubMed1999

[Fibrinolysis of intraventricular hematoma with rt-PA].

Intraventricular administration of recombinant tissue plasminogen activator (rt-PA) is an experimental therapy to hasten the lysis of intraventricular hemorrhages. We report nine patients (7 male, 2 female, mean age 64a) with intracerebral hematoma with ventricular extension who were treated with intraventricular infusion of rt-PA (2-32 mg, mean dose 17 mg). In two patients, clinically significant bleeding complications were associated with the fibrinolytic therapy. In one of these patients, fibrinolytic therapy was stopped. Other complications could not be observed. In eight of all nine patients, a rapid and extensive reduction of the amount of intraventricular blood occurred. A persistent shunt became necessary in two patients. We conclude, that intraventricular fibrinolysis probably leads to a faster clearance of intraventricular blood. Despite of fibrinolytic treatment, a permanent shunt becomes necessary in some cases. Intraventricular fibrinolysis is a potentially hazardous therapy with the risks of bleeding complications and infection.

Adult↗

PubMed1980

Heroin, but not levorphanol, produces explosive motor behavior in naloxone-treated rats.

Intraventricular infusions of heroin (an opiate) or levorphanol (an opioid) in rats produced rigidity but not explosive motor behavior (EMB). When preceded by an IP injection of naloxone, infusions of heroin but not levorphanol produced EMB. The results suggest that naloxone-antagonized effects of opiates mask EMB and that certain opioids do not induce EMB.

Animals↗

PubMed2000

A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning.

The neural cell adhesion molecule (NCAM) mediates cell adhesion and signal transduction through trans-homophilic- and/or cis-heterophilic-binding mechanisms. Intraventricular infusions of anti-NCAM have revealed a functional requirement of NCAM for the consolidation of memory in rats and chicks in a specific interval 6-8 h after training. We have now extended these studies to a synthetic peptide ligand of NCAM (C3) with an affinity for the IgI domain and the capability of inhibiting NCAM-mediated neurite outgrowth in vitro. Intraventricular administration of a single 5 microg bolus of C3 strongly inhibited recall of a passive avoidance response in adult rats, when given during training or in the 6-8-h posttraining period. The effect of C3 on memory consolidation was similar to that obtained with anti-NCAM as the amnesia was not observed until the 48-h recall time. The unique amnesic action of C3 during training could be related to disrupted NCAM internalization following training. In the 3-4-h posttraining period NCAM 180, the synapse-associated isoform, was down-regulated in the hippocampal dentate gyrus. This effect was mediated by ubiquitination and was prevented by C3 administration during training. These findings indicate NCAM to be involved in both the acquisition and consolidation of a passive avoidance response in the rat. Moreover, the study provides the first in vivo evidence for NCAM internalization in learning and identifies a synthetic NCAM ligand capable of modulating memory processes in vivo.

Animals↗

PubMed1981

Vasoactive intestinal polypeptide and the canine cerebral circulation.

A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP.

Animals↗

PubMed2003

NGF and NT-3 exert differential effects on the expression of neuropeptides in the suprachiasmatic nucleus of rats withdrawn from ethanol treatment.

Some neurotrophins have the capability of enhancing neuropeptide expression in several regions of the brain. It was also recently shown that NGF, infused over 1 month, offsets the decreased synthesis and expression of vasopressin (VP) and vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN) of rats submitted to chronic ethanol treatment and withdrawal. In the present study we examined the effectiveness of neutrotrophin-3 (NT-3) in promoting such effects, given that SCN neurons express both the high and the low affinity receptors for this neurotrophin. NT-3 was intraventricularly infused during 10 days to rats withdrawn from prolonged ethanol treatment. The total number, and the mean somatic volume, of VP- and VIP-immunoreactive neurons was compared with the estimates obtained from control rats and withdrawn rats treated with either NGF or cerebrospinal fluid during the same period. The infusion of cerebrospinal fluid and of NT-3 did not prevent the reduction in the number of peptide-producing neurons induced by withdrawal from ethanol treatment. Conversely, NGF infusion increased their number to control levels and led to neuronal hypertrophy. Our results show that, unlike NGF, NT-3 does not display the capacity of enhancing neuropeptide expression in the SCN. Because SCN neurons express the low affinity p75(NTR), which is equally activated by both neurotrophins, our results additionally indicate that the effects of NGF upon SCN neurons are not receptor-mediated. Taken together, our data suggest that indirect mechanisms, rather than direct neutrophin signaling, are likely to mediate the trophic effects exerted by NGF upon SCN neurons.

Animals↗

PubMed2002

Intake inhibition by NPY: role of appetitive ingestive behavior and aversion.

Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.

Animals↗

PubMed2006

beta-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or beta-amyloid deposits.

beta-Amyloid (Abeta) polypeptide plays a critical role in the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline of cognitive functions, formation of Abeta deposits and neurofibrillary tangles, and loss of neurons. Increased genetic production or direct intracerebral administration of Abeta in animal models results in Abeta deposition, gliosis, and impaired cognitive functions. Whether aging renders the brain prone to Abeta and whether inflammation is required for Abeta-induced learning deficits is unclear. We show that intraventricular infusion of Abeta1-42 results in learning deficits in 9-month-old but not 2.5-month-old mice. Deficits that become detectable 12 weeks after the infusion are associated with a slight reduction in Cu,Zn superoxide dismutase activity but do not correlate with Abeta deposition and are not associated with gliosis. In rats, Abeta infusion induced learning deficits that were detectable 6 months after the infusion. Approximately 20% of the Abeta immunoreactivity in rats was associated with astrocytes. NMR spectrum analysis of the animals cerebrospinal fluid revealed a strong reduction trend in several metabolites in Abeta-infused rats, including lactate and myo-inositol, supporting the idea of dysfunctional astrocytes. Even a subtle increase in brain Abeta1-42 concentration may disrupt normal metabolism of astrocytes, resulting in altered neuronal functions and age-related development of learning deficits independent of Abeta deposition and inflammation.

Aging↗

PubMed1975

Inefficiency of isoprenaline to induce drinking in the goat.

Isoprenaline, which acts as a potent dipsogen in water-satiated rats and dogs, did not elicit water intake when infused intravenously at 0.1 or 0.3 mu/kg min-1 in non-hydrated goats. Even the low dose of the drug caused a marked reduction of parotid salivary flow. The possibility is discussed that reduced salivary secretion might be the particular effect which makes isoprenaline dipsogenic in prandially drinking species. The intravenous infusion of isoprenaline at the high dose level caused an inhibition of the water diuresis of hydrated goats, concomitant with reduced renal Na+ excretion and a marked, sustained fall in the arterial blood pressure. Significant amounts of ADH were recovered from the urine secreted during the antidiuresis. This ADH-release was apparently not due to central beta-adrenergic stimulation since no inhibition of the water diuresis was observed during intraventricular infusions of isoprenaline. Rather, the ADH-release appears to have been secondary to the isoprenaline-induced fall in arterial blood pressure.

Animals↗

PubMed1988

Non-chromaffin tissue plus nerve growth factor reduces experimental parkinsonism in aged rats.

The mechanisms by which intrastriatal grafts of chromaffin tissue alleviate the signs of clinical and experimental parkinsonism remain elusive. In the present report, we have demonstrated that, in conjunction with intraventricular infusion of nerve growth factor (NGF), ventricular grafts of either non-chromaffin or adrenal medullary tissue are equally effective in reducing apomorphine-induced circling in rats whose substantia nigra have been permanently lesioned with 6-hydroxydopamine. These treatments were much more effective than implantation of adrenal medulla without NGF. In addition, the effects persisted indefinitely, though at a reduced level, after discontinuation of the NGF infusion. The results suggest that trophic factors may be crucial to the beneficial effects of intracerebral transplanted tissues.

Adrenal Medulla↗

PubMed1998

Attenuation of gonadotropin-releasing hormone reflex to coitus by alpha1-adrenergic receptor blockade in the rabbit.

The coitally induced gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge in the rabbit is preceded by an enhanced secretion of hypothalamic norepinephrine (NE). To investigate if adrenergic receptors are essential for the GnRH/LH surge, we administered a specific alpha1 receptor blocker, prazosin, into either the arcuate nucleus-median eminence (AME) or the third cerebroventricle (3rd V) of tethered, freely moving intact female rabbits via push-pull perfusion (PPP). Dual cannulae for PPP and drug infusion were placed stereotaxically either into the AME or AME and 3rd V of each rabbit after insertion of a permanent femoral venous catheter for serial blood sampling. During an experiment, continuous PPP samples and 10-min intermittent blood samples were collected for 5-6 hr. Females received either prazosin or control medium (artificial cerebrospinal fluid into an AME or saline into a 3rd V cannula) for 4 hr, beginning 1 hr before coitus. Intraventricular infusion of prazosin significantly (P < 0.05) suppressed both the postcoital GnRH and the LH surges. Administration of prazosin into the AME also attenuated the magnitude of the postcoital GnRH surge (P < 0.05) whereas postcoital LH values were not decreased below that of the control group (P > 0.05). The results suggest that alpha1 receptors are physiologically active in the initiation of the postcoital GnRH release. These findings, along with our earlier report of enhanced postcoital NE secretion, reinforce the hypothesis that NE plays an essential role in the preovulatory GnRH/LH surge in rabbits.

Adrenergic alpha-Antagonists↗

PubMed1999

Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats.

The levels of brain-derived neurotrophic factor (BDNF) vary between different forebrain areas and show region-specific changes after cerebral ischemia. The present study explores the possibility that the levels of endogenous BDNF determine the susceptibility to ischemic neuronal death. To block BDNF activity the authors used the TrkB-Fc fusion protein, which was infused intraventricularly in rats during 1 week before and 1 week after 5 or 30 minutes of global forebrain ischemia. Ischemic damage was quantified in the striatum and hippocampal formation after 1 week of reperfusion using immunocytochemistry and stereological procedures. After the 30-minute insult, there was a significantly lower number of surviving CA4 pyramidal neurons, neuropeptide Y-immunoreactive dentate hilar neurons, and choline acetyltransferase- and TrkA-positive, cholinergic striatal interneurons in the TrkB-Fc-infused rats as compared to controls. In contrast, the TrkB-Fc treatment did not influence survival of CA1 or CA3 pyramidal neurons or striatal projection neurons. Also, after the mild ischemic insult (5 minutes), neuronal death in the CA1 region was similar in the TrkB-Fc-treated and control groups. These results indicate that endogenous BDNF can protect certain neuronal populations against ischemic damage. It is conceivable, though, that efficient neuroprotection after brain insults is dependent not only on this factor but on the concerted action of a large number of neurotrophic molecules.

Animals↗