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Daily variations in the sensitivity of proestrous LH surge in the inhibitory effect of intraventricular injection of 5-HT or GABA in rats.

Intraventricular injection of 5-hydroxytryptamine (5-HT) into female rats at 11:00 h on the day of proestrus inhibited the preovulatory surge of luteinizing hormone (LH) and ovulation. A similar response was observed after the activation of the serotonergic system by stimulation of the median raphe nucleus. A diurnal rhythm of these responses was observed. In rats acclimated to a 14-h:10-h light:dark cycle the potency of 5-HT to inhibit the LH surge and ovulation was 2.06 and 2.3 times greater, respectively, when injected at 11:00 h than at 13:00 h. Also stimulation of the median raphe nucleus at 11:00 h was significantly more effective in inhibiting these parameters than stimulation at 13:00 h. Similarly, the ability of gamma-amino-butyric acid (GABA) to inhibit the preovulatory LH surge and ovulation was greater in rats injected in the morning than in the afternoon. The results of this study indicate that during proestrus the sensitivity of 5-HT and GABA to induce inhibition of preovulatory LH release and ovulation shows daily variations with maximal effect before the critical period.

Animals↗

Changes in succinate dehydrogenase activity of rats after intraventricular injections of GABA, muscimol and picrotoxin.

Effects of intraventricular injections of GABA, and a GABA agonist, muscimol and an antagonist, picrotoxin on succinate dehydrogenase (SDH) enzyme activity in plasma and a few hypothalamic nuclei of brain of rats have been investigated using biochemical, histochemical and cytophotometric techniques. Results show that SDH decreased by GABA and muscimol treatment, and increased after picrotoxin injection. From the above findings, it is apparent that GABA, muscimol and picrotoxin influence SDH activity of plasma and hypothalamic nuclei.

Animals↗

Epileptogenic action of intraventricularly injected antimelatonin antibody.

In rats, intraventricularly injected antimelatonin antibody caused the appearance of transitory epileptiform abnormalities. Epileptic activity arose from and was limited to the cortical mantle of the hemisphere ipsilateral to the injection side. The occasional occurrence of lateralized seizures has also been observed. Control injection of saline, of the vehicle (rabbit serum), or of antibody saturated with melatonin induced flattening and desynchronization of the electroencephalogram but not epileptiform activity. Repeated antimelatonin injections caused reappearance of the same type of epileptic abnormalities that lasted slightly longer than the first time. Melatonin may play an inhibitory role in neuronal excitability.

Animals↗

Immune response in draining lymph nodes and spleen after intraventricular injection of antigen.

Both Fischer 344 and Sprague Dawley rats showed significant numbers of antibody forming cells (PFC) in deep cervical lymph nodes after intraventricular injection of antigens, including trinitrophenylated (TNP)-hemocyanin, TNP-B. abortus and sheep erythrocytes. This indicated that particular as well as soluble antigens drained to these lymph nodes from the spinal fluid. Other lymph nodes examined did not show increased PFC over background, but levels of PFC in the spleen were significantly elevated after intraventricular injection of each of these antigens. Comparison with dose responses in the spleen after intravenous antigen injection suggested that approximately 20% of the intraventricularly injected immunogens drained to the peripheral blood. The relevance of these findings with respect to the brain as an immunologically privileged site is discussed.

Animals↗

Myelin changes in the rats CNS following intraventricular injection of serum.

Normal human or rat serum administered by intraventricular injection induced demonstrable changes in the rat CNS myelin as seen from an increased recovery of dissociated myelin (DM), i.e. a myelin-related low density membrane fragments, from the tissue homogenates. The yield of DM reached a maximum on the third postinjection day and returned to the control level by day 5. In spite of the increased recovery of DM, no physico-chemical alternations in myelin isolates and no histological abnormalities in the tissue could be detected. The production of DM seems to be a sensitive index of serum-induced alteration of the myelin sheath.

Animals↗

Effects of intraventricular injections of 6-hydroxydopamine on anterior pituitary cell proliferation.

Effects of intraventricular injections of 6-hydroxydopamine (6-OHDA; 200 micrograms/20 microliter vehicle) on anterior pituitary cell proliferation in rats have been investigated by means of the colchicine metaphase-arrest technique. In those groups of animals receiving 6-OHDA alone or 6-OHDA plus desmethylimipramine (DMI, 25 mg/kg body weight i.p.), where the mean mitotic activity rates (MMARs) were initially low at 48 hours, an increase of MMARs was observed at 96 and 144 hours after the drug injections. At 144 hours after drug administration, the MMARs values in the 6-OHDA-injected group and in the 6-OHDA + DMI-treated group were significantly higher than those in the control groups. This increase of MMARs resulted from the enhancement of acidophilic and chromophobe cell proliferation. The low MMARs at 48 hours after 6-OHDA injection are probably a result of dopamine release from damaged nerve endings; the enhancement of MMARs (particularly evident in the 6-OHDA + DMI-treated group) at 96 and 144 hours after drug administration is presumably related to a deficiency of dopaminergic control of anterior pituitary cell proliferation.

Animals↗

[The biopolymer metabolism of the connective tissue in the aorta under intraventricular injections of neuropeptides].

The metabolism of connective tissue biopolymers in the blood serum and in the aorta under repeated intraventricular injections of P-substance, L-enkephalin and B-endorphine was studied in chronic experiments on rabbits. The alternations of the central neurochemical processes, caused by prolonged intraventricular injections of neuropeptides were proved to lead to intensification of metabolic processes in the connective tissue characterized by the accumulation of its biopolymers in the aorta wall. The injection of P-substance, in contrast to opioid peptides, is accompanied by more marked alternations.

Animals↗

The histologic effect of intraventricular injection of metrizamide.

A patient with sudden apoplexy and coma was found to have hydrocephalus on computed tomographic scan, and metrizamide was instilled into the ventricles. Subsequent autopsy disclosed a brainstem infarct secondary to a primary dissecting aneurysm of the basilar artery, and a histologic picture of encephalitis in the walls of the lateral and third ventricles. Metrizamide may cause pathologic changes that must be recognized for the correct interpretation by the pathologist of tissue sections previously exposed to metrizamide. In the present case, the changes were seen 11 days after exposure of the tissue to metrizamide, consonant with the time course of similar changes observed in animals. The localization of the cellular infiltrates to the Virchow-Robin spaces corroborates evidence from the literature that metrizamide enters brain parenchyma via these spaces.

Adult↗

Normal cerebrospinal fluid dynamics. A study with intraventricular injection of 111In-DTPA in leukemia and lymphoma without meningeal involvement.

The cerebrospinal fluid flow pattern in seven patients with leukemia or lymphoma, but without prior meningeal or cerebral disease, was studied following introduction of indium-diethylenetriamine pentaacetic acid In-DTPA 111 in a lateral ventricle through an Ommaya reservoir. The time to egress from the ventricular system into the basal cisterns was variable but generally short. One hour after administration, the basal cisterns were clearly visible in all patients. Thereafter, kinetics throughout the cranial and spinal subarachnoid space were consistent. The flow patterns of three patients cured of meningeal dissemination and one patient with mild meningeal leukemia were similar to the normal pattern.

Adolescent↗

Cell death of adult pyramidal CA1 neurons after intraventricular injection of a novel peptide derived from trkA.

Members of the nerve growth factor (NGF) family of neurotrophins bind to the second leucine-rich motif (LRM2) within the extracellular domains of their respective receptors (trkA, trkB, trkC). Small LRM2 peptides have been recently demonstrated to selectively bind the neurotrophins revealing similar complex binding characteristics as full-length receptors. We extend our recent findings, showing that the peptides (A and C) do not block nerve fiber outgrowth through high affinity trk receptors in a ganglia bioassay. Since the highest concentration of neurotrophins [NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3)] is found in the hippocampus, the peptides were injected into the 3rd ventricle of anesthetized adult rats. The (NGF binding) LRM2-A peptide, but not the (BDNF binding) LRM2-B or the (NT-3 binding) LRM2-C peptides, caused severe apoptotic neurodegeneration of hippocampal pyramidal CA1 neurons as revealed by cresyl violet staining and the TUNEL reaction. The degeneration was protected by intrahippocampal injection of NGF-beta and by the non-N-methyl-D-aspartate (NMDA) antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), indicating a glutamatergic mechanism. In situ hybridization revealed that pyramidal CA1 neurons did not express trkA and p75 receptor mRNA in sham and LRM2-A-lesioned animals. It is concluded that the LRM2-A peptide represents a novel peptide with properties to induce apoptotic cell death of pyramidal CA1 neurons and may be useful as an experimental agent.

2-Amino-5-phosphonovalerate↗

Absence of germline infection in male mice following intraventricular injection of adenovirus.

The possibility of inadvertent exposure of gonadal tissue to gene therapy vectors has raised safety concerns about germline infection. We show here that the receptor for coxsackie B viruses and adenoviruses 2 and 5 (CXADR) is expressed in mouse germ cells, suggesting the possibility that these viruses could infect germ cells. To directly assess the risk of germline infection in vivo, we injected an adenovirus carrying the germ-cell-specific protamine promoter fused to the bacterial lacZ reporter gene into the left ventricular cavity of mice and then monitored expression of the reporter gene in germ cells. To differentiate between infection of stem cells and differentiating spermatogenic cells, we analyzed expression of the reporter cassette at different times after viral delivery. Under all conditions tested, mice did not express the Escherichia coli beta-galactosidase protein in developing spermatids or in mature epididymal spermatozoa. Primary germ cells cultured in vitro were also refractory to adenoviral infection. Our data suggest that the chance of vertical germline transmission and insertional mutagenesis is highly unlikely following intracoronary adenoviral delivery.

Adenoviridae↗