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PubMed1989

Increase in the blood pressure and decrease in the norepinephrine release in the ventrolateral medulla during intraventricular administration of hypertonic NaCl.

Norepinephrine (NE) release in the ventrolateral medulla (VLM) was serially measured in anesthetized male Wistar rats during the rise in the blood pressure (BP) produced by acute intraventricular (ICV) administration of hypertonic (1.5 M) NaCl. Catecholamine release was determined by a brain microdialysis method using high performance liquid chromatography and electrochemical detector. The release of NE in the VLM was significantly decreased after ICV 1.5 M NaCl. In another set of rats, the pressor response to acute ICV 1.5 M NaCl was attenuated by selective administration of NE to the VLM using the microdialysis method. Chronic and continuous ICV infusion of 1.5 M NaCl to conscious rats caused an increase in BP on day 10 which was associated with a decrease in NE release in the VLM; concomitant ICV infusion of NE or of a synthetic NE precursor, L-threo-3,4-dihydroxyphenylserine (L-DOPS) prevented the rise in BP as well as the reduction in NE release. These results suggest that a decrease in the NE release of the VLM may contribute to the change in BP induced by ICV infusion of hypertonic saline.

Animals↗

PubMed2001

Effect of probenecid on ventricular cerebrospinal fluid methotrexate pharmacokinetics after intralumbar administration in nonhuman primates.

PURPOSE: Intrathecal methotrexate (MTX) achieves high concentrations in the cerebrospinal fluid (CSF) following intralumbar administration. However, peak ventricular CSF MTX concentrations are highly variable and are < 10% of those achieved with intraventricular dosing. The objectives of this study were to evaluate the effect of intralumbar and intravenous probenecid on ventricular CSF MTX concentrations after intralumbar administration of MTX, and to compare the pharmacokinetics of MTX after intralumbar and intraventricular administration. METHODS: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received 0.5 mg intraventricular (lateral ventricle) MTX, or 0.5 mg intralumbar MTX with and without intralumbar or intravenous probenecid. Animals were kept prone for 1 h after MTX administration, and ventricular CSF was sampled up to 48 h from a fourth ventricular Ommaya reservoir. MTX concentrations were measured using the dihydrofolate reductase enzyme inhibition assay. Area under the ventricular CSF MTX concentration-time curve (AUC) was used as a measure of MTX exposure. RESULTS: Peak ventricular CSF MTX concentrations and AUCs were highly variable after intralumbar MTX administration. Ventricular CSF MTX AUCs increased by a mean of 3.2-fold after the addition of intralumbar probenecid. Intravenous administration of probenecid did not result in an increase in ventricular CSF MTX AUCs. Asymptomatic pleocytosis was observed in all animals after intralumbar probenecid administration. Ventricular CSF MTX concentrations and AUCs were less variable after intraventricular administration of MTX. CONCLUSION: The administration of intralumbar but not intravenous probenecid increases the ventricular CSF MTX exposure after intralumbar MTX administration.

Animals↗

PubMed2003

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy.

OBJECT: Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. METHODS: Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five(median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 +/- 0.4 micro/ml in Group 1 and 565.58 +/- 168.71 microg/ml 1 hour after vancomycin application in Group 2 (mean +/- standard deviation). Vancomycin levels above the recommended trough level of 5 microg/ml in CSF were never reached in Group 1, whereas in Group 2 they below the trough level (3.74 +/- 0.66 microg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. CONCLUSIONS: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Adult↗

PubMed1983

Amino acids injected into the cerebroventricular system induce an enhancement of reflex bradycardia in the rat.

The effects of administration of taurine, GABA and glycine, into the lateral cerebral ventricle, on cardiovascular function were assessed in urethane-anaesthetized rats. Intraventricular administration of either taurine (10-30 micrograms), GABA (5-20 micrograms) or glycine (5-20 micrograms) caused a dose-dependent decrease in both the heart rate and the mean arterial pressure. For example, both the heart rate and the mean arterial pressure fell almost immediately and reached their minimum levels about 5 min after an injection of 20 micrograms of taurine. The cardiovascular responses recovered about 30 min after the injection of taurine. Also, reflex bradycardia was produced in the rats by intravenous infusion of adrenaline (1-5 micrograms/kg). Intraventricular pretreatment of the rats with either taurine, GABA or glycine, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, pretreatment of the rats intravenously with the same dose of taurine, GABA or glycine had no effect on the adrenaline-induced bradycardia. These data indicate that these amino acids act through a central mechanism to facilitate reflex bradycardia mediated through baroceptor reflexes in response to an acute increase in arterial pressure.

Amino Acids↗

PubMed2003

Treatment of CNS lymphoma with the anti-CD20 antibody rituximab: experience with two cases and review of the literature.

Treatment with radio- and chemotherapy has become increasingly efficient in primary CNS lymphoma (PCNSL). However, time to tumor progression is often short, and the majority of patients eventually relapse. Therefore, new therapeutic modalities are needed. One possible new option is the use of monoclonal antibodies (moabs) such as the humanized anti-CD20 moab rituximab. Treatment with intravenous rituximab has resulted in response rates of 50% in systemic non-Hodgkin's lymphoma and was also efficient in PCNSL as well as in CNS involvement of systemic disease. However, rituximab concentrations in the cerebrospinal fluid are low after systemic application. Therefore, the authors performed an intraventricular rituximab treatment in 2 patients. The most recent results and the possible role of moabs in patients with PCNSL are summarized and discussed.

Adult↗

PubMed2003

Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.

CONTEXT: Newborns admitted to neonatal intensive care units (NICUs) undergo a variety of painful procedures and stressful events. Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematically, there is confusion regarding whether morphine should be used routinely in this setting. OBJECTIVE: To evaluate the effects of continuous intravenous morphine infusion on pain responses, incidence of intraventricular hemorrhage (IVH), and poor neurologic outcome (severe IVH, periventricular leukomalacia, or death). DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherlands of 150 newborns who had received ventilatory support (inclusion criteria: postnatal age younger than 3 days and ventilation for less than 8 hours; exclusion criteria: severe asphyxia, severe IVH, major congenital malformations, and administration of neuromuscular blockers). INTERVENTIONS: Intravenous morphine (100 microg/kg and 10 microg/kg per hour) or placebo infusion was given for 7 days (or less because of clinical necessity in several cases). MAIN OUTCOME MEASURES: The analgesic effect of morphine, as assessed using validated scales; the effect of morphine on the incidence of IVH; and poor neurologic outcome. RESULTS: The analgesic effect did not differ between the morphine and placebo groups, judging from the following median (interquartile range) pain scores: Premature Infant Pain Profile, 10.1 (8.2-11.6) vs 10.0 (8.2-12.0) (P =.94); Neonatal Infant Pain Scale, 4.8 (3.7-6.0) vs 4.8 (3.2-6.0) (P =.58); and visual analog scale, 2.8 (2.0-3.9) vs 2.6 (1.8-4.3) (P =.14), respectively. Routine morphine infusion decreased the incidence of IVH (23% vs 40%, P =.04) but did not influence poor neurologic outcome (10% vs 16%, P =.66). In addition, analyses were adjusted for the use of additional open-label morphine (27% of morphine group vs 40% of placebo group, P =.10). CONCLUSIONS: Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a standard of care in preterm newborns who have received ventilatory support. Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity.

Analgesics, Opioid↗

PubMed1978

Intraventricular and parenteral gentamicin therapy for ventriculitis in children.

Five children with intraventricular shunts developed ventriculitis due to organisms resistant to multiple antimicrobial agents but sensitive to gentamicin sulfate. No gentamicin was detected in ventricular CSF of four patients at a time when gentamicin was being administered only intravenously. The intraventricular administration of 1 mg of gentamicin resulted in ventricular CSF concentrations greater than 20 microgram/ml one hour and 5 to 14 microgram/ml 36 hours after administration. Patients were treated with intraventricularly given gentamicin for an average of 16 days, with no apparent complications or relapses during the 12- to 24-month follow-up period. Intraventricularly administered gentamicin sulfate (1 mg every 24 to 36 hours) in conjunction with complete shunt removal was an effective means of therapy of ventriculitis caused by bacteria resistant to antibiotics that readily penetrate the blood-brain barrier.

Cerebral Ventricles↗

PubMed1986

Intraventricular bombesin can decrease single meal size in the baboon.

We have reported that intravenous bombesin decreases single meal size in a dose-dependent manner. The present study tests whether intraventricular bombesin is also effective in decreasing single meal size. Doses of bombesin (0.1-4 micrograms/kg) were administered both intravenously and intraventricularly. A median dose of 1 microgram/kg bombesin decreased 30 min meal size about 50%, whereas a median dose of 1 microgram/kg given intravenously only decreased meal size 25%. We conclude that bombesin given centrally in the baboon can decrease meal size and that this effect does not appear to be due to leakage into the periphery.

Animals↗

PubMed1977

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species. These observations validate this experimental primate model and indicate its potential application to the pharmacological study of CNS chemotherapeutic agents in man.

Animals↗

PubMed1990

Mucor cerebral abscess associated with intravenous drug abuse.

We report on a case of a 26-year-old intravenous narcotic abuser with a primary cerebral mucormycotic abscess caused by Rhizopus oryzae. He was treated with a combination of intravenous and intraventricular amphotericin B and surgical drainage with a successful outcome. There was no evidence that his infection was acquired by the rhinocerebral route, it seems likely that he injected himself with a contaminated batch of narcotic or amphetamine. Mucormycosis presenting in this way has been described previously but this is only the second such case to survive. Early diagnosis and treatment is essential for a favourable outcome in this condition.

Adult↗

PubMed1987

The effect of intraventricular blood on cerebral blood flow in newborn dogs.

We investigated the effect of intraventricular blood on cerebral blood flow in the newborn puppy by infusing autologous blood into the lateral ventricle to produce and maintain an intraventricular pressure of approximately 15 mm Hg (mild insult), 30 mm Hg (moderate insult), or 50 mm Hg (severe insult) for 20 min. As the intraventricular pressure increased, flow decreased progressively to all areas of the brain directly proportional to the cerebral perfusion pressure. On return of the intraventricular pressure to baseline level, cerebral blood flow normalized despite the continued presence of a large amount of blood within the lateral ventricles. We suggest that blood within the ventricular system can result in a significant acute reduction of cerebral blood flow which appears to be mediated through the effect on cerebral perfusion pressure.

Animals↗

PubMed1977

Role of central and peripheral mechanisms in the action of alpha-methyldopa on blood pressure and renin secretion.

The mechanism by which alpha-methyldopa lowers arterial pressure and suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were prevented by adjusting a suprarenal aortic clamp. After intravenous alpha-methyldopa (100 mg/kg) mean arterial pressure (MAP) decreased form 127+/-3 to a mean minimum of 107+/-4 mm Hg (P less than .01) and plasma renin activity (PRA) decreased from 20.6+/-4.8 to 10.9+/-1.7 ng/ml/3 hr (P less than .05). Blockade of peripheral dopa decarboxylase with intravenous carbidopa (20 mg/kg) significantly attenuated the hypotensive action of intravenous alpha-methyldopa but MAP still decreased from 145+/-6 to 130+/-5 mm Hg(P less than .001). Intravenous carbidopa completely abolished the fall in PRA produced by intravenous alpha-methyldopa (16.8+/-2.8 to 16.9+/-2.1 ng/ml/3 hr.) Intraventricular carbidopa (3 microng/kg/min) did not block the hypotensive (135+/-8 to 113+/-7 mm Hg, P less than .01) or renin-lowering effect (24.3+/-5 to 13.4+/-3.2 ng/ml/3 hr, P less than .01) of intravenous alpha-methyldopa (0.5 mg/kg decreased MAP from 118 +/- 5 to 104 +/- 5 mm Hg (P less than 0.001) but had no effect on PRA (23.4+/-6 TO 19.4+/-7 NG/ML/3 hr.) Intraventricular alpha-methylnorepinephrine (2 microng/kg) also decreased MAP from 127+/-5 to 112+/-3mm Hg (P less than .006) but again failed to significantly alter PRA (36.1+/-11.8 to 37.2+/-15 ng/ml/3 hr). These results indicate that there is both a central and peripheral component to the antihypertensive effect of alpha-methyldopa in the dog and that the suppression of renin secretion results from a peripheral action of the drug.

Animals↗

PubMedDate not supplied

Amphotericin B and imidazole therapy for coccidioidal meningitis in children.

Coccidioidal meningitis is a fatal form of Coccidioides immitis infection. Amphotericin B (AMB) therapy has reduced mortality but is itself toxic, and experience with it in very young children is meager. We are treating six children for coccidioidal meningitis diagnosed at 19 to 74 months of age. All had acute hydrocephalus and ventriculitis. The first four patients were initially treated with AMB but were changed to imidazole therapy (miconazole and ketoconazole). In the last two patients therapy was begun with the imidazoles. Ommaya reservoirs for cisternal therapy have been of limited usefulness. AMB therapy has been limited by local and systemic toxicity and by failure in one case. All children have improved with 15 to 22 mg oral ketoconazole per kg per day and 3 to 5 mg intraventricular miconazole for instillation therapy, including those with noncommunicating hydrocephalus in whom the intraventricular drug does not reach the basilar cisterns. Peak concentrations of ketoconazole in ventricular fluid were 0.08 to 5.6 micrograms/ml. Shunt obstruction and bacterial superinfections have been the major causes of morbidity. Imidazole therapy of coccidioidal meningitis may be more effective than is AMB in young children, and it offers the advantages of fewer side effects and not requiring intrathecal or cisternal administration.

Amphotericin B↗

PubMed1985

Ceftazidime in the therapy of pseudomonal meningitis.

In this study we report about the efficacy and tolerability of ceftazidime in the treatment of 10 cases of pseudomonal meningitis (nine Pseudomonas aeruginosa and one Pseudomonas cepacia). The 10 patients had a pseudomonal infection of the central nervous system (CNS) complicating neurosurgical procedures or developed on a preexisting immunodepressing condition; four patients were of pediatric age. All isolates were sensitive to ceftazidime with MICs ranging from 0.39 to 3.12 micrograms/ml. Ceftazidime was given intravenously at the dosage of 100-150 mg/kg/day. In seven cases amikacin was associated by intralumbar or intraventricular instillation. The duration of ceftazidime treatment ranged from 9 to 49 days with a mean of 22.2. Eight cases out of ten were cured bacteriologically and clinically, while the remaining two were cured after treatment with other antibiotics. Concentrations of ceftazidime in serum and in lumbar and/or ventricular cerebrospinal fluid (CSF) were obtained in four cases; the mean concentration in lumbar CSF was 12.2 micrograms/ml and in ventricular 3.3 micrograms/ml. The study demonstrated that ceftazidime is effective in the treatment of Pseudomonal meningitis.

Adolescent↗

PubMed1978

Influence of intraventricularly applied apomorphine on somato-vegetative reflexes in cats.

To obtain information about the dopaminergic neurotransmission processes taking part in the somatovegetative reflexes the effects of intraventricularly given apomorphine were studied in lightly anaesthetized cats. The level of blood pressure and the reflexogenic hypertension due to central sciatic nerve stimulation were not changed when apomorphine was applied into the lateral and third but was inhibited when given into the fourth ventricle. The nictitating membrane contractions elicited by sciatic nerve stimulation were inhibited by apomorphine when introduced into each part of the ventricular system. Thus the inhibitory dopaminergic synapses located in the structures lining the walls of the brain ventricular system reached by apomorphine appear to be involved in the central control of somato-vegetative reflexes.

Animals↗

PubMed1991

Ultrastructural changes of crop-sac and lactotrophs after systemic or intraventricular administration of drugs enhancing cholinergic transmission in pigeons.

The ultrastructural effects of drugs enhancing, by different mechanisms, cholinergic transmission in the crop-sac (the target for prolactin secretion in birds) and the anterior pituitary lactotrophs, were studied in pigeons (Columba livia). The systemic or intraventricular administration of physostigmine, carbachol and muscarine produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ultrastructural changes in the lactiferous areas through scanning and transmission electron microscopy of the crop-sac mucosa. A marked activation was also observed in anterior pituitary lactotrophs. Crop-sac and anterior pituitary lactotrophs stimulatory effects were prevented by an atropine pretreatment, but not by mecamylamine and pempidine pretreatments. The present results suggest that muscarinic receptors at the hypothalamic and/or anterior pituitary level are involved in avian species in the control of prolactin secretion.

Animals↗

PubMed2005

Comparison of ischemia-directed migration of neural precursor cells after intrastriatal, intraventricular, or intravenous transplantation in the rat.

Cell replacement therapy may have the potential to promote brain repair and recovery after stroke. To compare how focal cerebral ischemia affects the entry, migration, and phenotypic features of neural precursor cells transplanted by different routes, we administered neuronal precursors from embryonic cerebral cortex of green fluorescent protein (GFP)-expressing transgenic mice to rats that had undergone middle cerebral artery occlusion (MCAO) by the intrastriatal, intraventricular, and intravenous routes. MCAO increased the entry of GFP-immunoreactive cells, most of which expressed neuroepithelial (nestin) or neuronal (doublecortin) markers, from the ventricles and bloodstream into the brain, and enhanced their migration when delivered by any of these routes. Transplanted neural precursors migrated into the ischemic striatum and cerebral cortex. Thus, transplantation of neural precursors by a variety of routes can deliver cells with the potential to replace injured neurons to ischemic brain regions.

Animals↗

PubMedDate not supplied

Intraventricular xenografts: chronic injection of antibodies into the CSF provokes granulomatosis reactions but Ia antibodies do not enhance graft survival.

We have studied the influence of chronic infusions of antibodies against Ia antigen into the CSF on immunological reactions to intraventricular xenografts in rats. The antibodies were infused with osmotic pumps implanted one day before grafting. One set of control groups consisted of animals with xenografts which simultaneously received antibody against penicillin or vehicle with no antibody. In a second set of control groups, antibodies against Ia antigen, penicillin, rat anti-mouse IgG or vehicle (no antibody) were administered alone, without grafts. In the animals that received infusions of antibodies against either Ia antigen or penicillin plus xenografts, intense granulomatosis reactions were observed in the host brains. These reactions were not observed in the animals that received antibody infusions without xenografts. It appears that this reaction was produced by the massive and persistent injection of immunoglobulins, together with the presence of xenograft tissue. The chronic infusion of Ia antibodies did not prolong xenograft survival.

Animals↗