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Intracerebroventricular Injection (intracerebroventricular + injection)
Selected AbstractsIntracerebroventricular Injections of Prolactin Counteract the Antagonistic Effect of Bromocriptine on Rabbit Maternal BehaviourJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2004G. González-Mariscal Abstract To investigate the participation of prolactin in nest-building and maternal behaviour in rabbits, we administered (from pregnancy day 26 to parturition) rabbit prolactin (rbPRL; or vehicle) intracerebroventricularly (i.c.v.) to primiparous animals injected with bromocriptine subcutaneously (s.c.). Control females (given vehicle s.c. and i.c.v.) built a maternal nest (of straw and body hair) in 77% of cases. This proportion decreased to 19% in the bromocriptine-only group (P < 0.05) and increased to 93% in the group given bromocriptine plus rbPRL (P > 0.05). Maternal behaviour (i.e. the adoption of a crouching posture over the litter inside the nest box) was expressed by 77% of control rabbits, 19% of bromocriptine-only animals (P < 0.05) and 57% of females given bromocriptine plus rbPRL (P > 0.05). Values of nonmaternal activities (i.e. scent-marking, ambulation in an open field) were similar among the three studied groups. These results suggest that prolactin, acting in late pregnancy, plays a major role in the stimulation of nest-building and maternal behaviour in rabbits. [source] Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase-2 in brain endothelial cells and also upregulate their receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Chunyu Cao Abstract Peripheral immunological insults induce interleukin (IL)-1, and IL-6 in the brain. To elucidate the mechanism(s) of fever evoked by these brain-derived cytokines, and possible interactions between them, we examined in rats: (i) whether cyclooxygenase-2 is responsible for fever evoked by central injection of these cytokines; (ii) if so, where in the brain cyclooxygenase-2 is induced; (iii) where the receptors for these cytokines are located; and (iv) how the expression of these receptors is influenced by the cytokines. Intracerebroventricular injection of these cytokines evoked fever that was suppressed by a cyclooxygenase-2 inhibitor. Brain endothelium was the site of cyclooxygenase-2 induction by these cytokines. IL-1 receptor (IL-1R) was constitutively expressed in brain endothelium, and its mRNA was further upregulated by either cytokine. IL-6R mRNA was constitutively expressed in the cerebral cortex, and was newly induced in as yet unidentified cells in brain blood vessels by either cytokine. Messenger RNAs for cyclooxygenase-2, IL-1R, and IL-6R were often observed in the same blood vessels. These results suggest that COX-2 induced in brain endothelium is, at least in part, involved in the fever evoked by these cytokines, and that one possible interaction between these two cytokines is mutual upregulation of their receptors in the endothelium or perivascular cells, resulting in augmentation of their actions. [source] Hypothalamic-Pituitary-Adrenal Responses to Centrally Administered Orexin-A are Suppressed in Pregnant RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2003P. J. Brunton Abstract Orexins are hypothalamic neuropeptides that stimulate arousal and food intake but also activate the hypothalamic-pituitary-adrenal (HPA) axis. During late pregnancy in the rat, the responsiveness of the HPA axis to stressors is attenuated, and thus we investigated HPA axis responses to centrally administered orexin-A during pregnancy. Intracerebroventricular injection of orexin-A (0.5 µg, 140 pmol) significantly increased plasma adrenocorticotropic hormone and corticosterone concentration within 10 min in virgin female Sprague-Dawley rats, but had no effect in day 21 pregnant rats. Orexin-A significantly increased corticotropin-releasing hormone (CRH) mRNA expression, measured by in situ hybridization, in the paraventricular nucleus (PVN) of the virgin group but not in the pregnant group. Thus, the responsiveness of PVN CRH neurones to orexin-A, and hence the pituitary-adrenal axis, is markedly reduced in pregnancy. This may favour anabolic adaptations in pregnancy. [source] Modulation of hepatic cytochrome P450 during Listeria monocytogenes infection of the brainJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2003Elena Garcia Del Busto Cano Abstract Hepatic cytochrome P450 enzymes can be modulated during systemic infections. Inflammatory responses in the brain have also been shown to cause a significant decrease in the levels and activities of important cytochrome P450 isoforms in the liver. We determined some of the effects of central nervous system (CNS) Listeria monocytogenes infection on hepatic cytochrome P450 systems in rats. Intracerebroventricular injection of L. monocytogenes resulted in a time-dependent modulation of CYP1A, CYP2B, and CYP3A activities in the liver. Total hepatic cytochrome P450 content was significantly lowered 48 h after administration of the bacterium, and hepatic CYP1A and CYP2B activities were significantly altered 48 and 72 h after infection, respectively, whereas CYP3A activity and protein content were depressed 72 h after the insult. Bacterial load in the brain increased dramatically over a 72-h period, but the number of bacteria cultured from liver over this time period was relatively small. Therefore, an infection largely confined to the CNS in the rat results in abnormal activity levels of certain hepatic cytochrome P450 enzymes crucial in drug metabolism. If such a response also occurs in humans, this has the potential to produce serious complications with drug and endogenous substrate metabolism in patients with an infectious disease involving the CNS. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1860,1868, 2003 [source] Intracerebroventricular injection of L-aspartic acid and L-asparagine induces sedative effects under an acute stressful condition in neonatal chicksANIMAL SCIENCE JOURNAL, Issue 3 2009Haruka YAMANE ABSTRACT The present study was conducted to clarify the central functions of L-aspartic acid (Asp) and L-asparagine (Asn) during an acute stressful condition in chicks. Intracerebroventricular (i.c.v.) injection of Asp and Asn (0.84 µmol) attenuated the vocalization that normally occurs during social separation stress. Asp decreased the time spent in active wakefulness and induced sedation. Asn had a similar effect to Asp, although somewhat weaker. However, i.c.v. injection of Asp and Asn further enhanced plasma corticosterone release under social separation stress. Taken together, the i.c.v. injection of Asp and Asn has sedative effects under an acute stressful condition, which does not involve the hypothalamic-pituitary-adrenal axis. [source] Blood,brain barrier breakdown and repair by Src after thrombin-induced injuryANNALS OF NEUROLOGY, Issue 4 2010Da-Zhi Liu PhD Objective Thrombin mediates the life-threatening cerebral edema that occurs after intracerebral hemorrhage. Therefore, we examined the mechanisms of thrombin-induced injury to the blood,brain barrier (BBB) and subsequent mechanisms of BBB repair. Methods Intracerebroventricular injection of thrombin (20U) was used to model intraventricular hemorrhage in adult rats. Results Thrombin reduced brain microvascular endothelial cell (BMVEC) and perivascular astrocyte immunoreactivity,indicating either cell injury or death,and functionally disrupted the BBB as measured by increased water content and extravasation of sodium fluorescein and Evans blue dyes 24 hours later. Administration of nonspecific Src family kinase inhibitor (PP2) immediately after thrombin injections blocked brain edema and BBB disruption. At 7 to 14 days after thrombin injections, newborn endothelial cells and astrocytes were observed around cerebral vessels at the time when BBB permeability and cerebral water content resolved. Delayed administration of PP2 on days 2 through 6 after thrombin injections prevented resolution of the edema and abnormal BBB permeability. Interpretation Thrombin, via its protease-activated receptors, is postulated to activate Src kinase phosphorylation of molecules that acutely injure the BBB and produce edema. Thus, acute administration of Src antagonists blocks edema. In contrast, Src blockade for 2 to 6 days after thrombin injections is postulated to prevent resolution of edema and abnormal BBB permeability in part because Src kinase proto-oncogene members stimulate proliferation of newborn BMVECs and perivascular astrocytes in the neurovascular niche that repair the damaged BBB. Thus, Src kinases not only mediate acute BBB injury but also mediate chronic BBB repair after thrombin-induced injury. ANN NEUROL 2010;67:526,533 [source] Intracerebroventricular Effects of Histaminergic Agents on Morphine-Induced Anxiolysis in the Elevated Plus-Maze in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2005Mohammad-Reza Zarrindast It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine-induced anxiolysis in rats, using elevated plus-maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 ,g/rat) also increased anxiety-related behaviours. Intracerebroventricular injection of pyrilamine, a H1 receptor antagonist (25, 50 and 100 ,g/rat), increased anxiety whereas injection of ranitidine, a H2 receptor antagonist (5, 10 and 20 ,g/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H2 receptors, while the response of H1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 ,g/rat), pyrilamine (50 ,g/rat) and ranitidine (5 ,g/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 ,g/rat), pyrilamine (25, 50 and 100 ,g/rat) or ranitidine (5, 10 and 20 ,g/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety-related indices in the elevated plus-maze. This may imply that morphine-induced anxiolysis probably is independent of the histaminergic system. [source] Cardiovascular Actions of Orexin-A in the Rat Subfornical OrganJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2007P. M. Smith Orexin-A is a neuropeptide, primarily produced in the lateral hypothalamic/perifornical hypothalamus. Orexin receptors and immunoreactive neuronal fibres are widely distributed throughout the brain, suggesting integrative neurotransmitter roles in a variety of physiological systems. Intracerebroventricular injections of orexin-A increase blood pressure and stimulate drinking, and the subfornical organ (SFO), a circumventricular structure implicated in autonomic control, is a potential site at which orexin may act to exert these effects. We have therefore used microinjection techniques to examine the effects of orexin-A administered directly into the SFO on blood pressure and heart rate in urethane anaesthetised male Sprague-Dawley rats. Orexin-A microinjection (50 fmol) into the SFO caused site-specific decreases in blood pressure (SFO: mean area under curve (AUC) = ,681.7 ± 46.8 mmHg*s, n = 22 versus non-SFO: 63.68 ± 54.69 mmHg*s, n = 15, P < 0.001), and heart rate (SFO: mean AUC = ,26.7 ± 2.8 beats, n = 22, versus non-SFO: mean AUC = 1.62 ± 2.1 beats, n = 15, P < 0.001). Vagotomy did not alter the hypotensive or bradycardic responses elicited by orexin-A microinjection. Prior ,-adrenoceptor blockade with phenoxybenzamine (1 mg/kg, i.v.) masked the orexin-A induced blood pressure (mean AUC = ,122.6 ± 17.6 mmHg*s, n = 4, P < 0.01 paired t-test) and heart rate (mean AUC = ,6.7 ± 1.7 beats, n = 4, P < 0.05, paired test) response. The orexin-A induced heart rate response was attenuated when ,-adrenoceptors were blocked with propranolol (1 mg/kg, i.v.; mean AUC = 0.6 ± 2.8 beats, n = 5, P < 0.01 paired t-test). These studies demonstrate that microinjection of orexin-A into the SFO causes site specific decreases in blood pressure and heart rate which is mediated by a reduction in sympathetic tone. [source] Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2005Wei-Lin Chien Abstract Memory is one of the most fundamental mental processes, and various approaches have been used to understand the mechanisms underlying this process. Nitric oxide (NO), cGMP and protein kinase G (PKG) are involved in the modulation of synaptic plasticity in various brain regions. YC-1, which is a benzylindazole derivative, greatly potentiated the response of soluble guanylate cyclase to NO (up to several hundreds fold). We have previously shown that YC-1 markedly enhances long-term potentiation in hippocampal and amygdala slices via NO-cGMP-PKG-dependent pathway. We here further investigated whether YC-1 promotes learning behaviour in Morris water maze and avoidance tests. It was found that YC-1 shortened the escape latency in the task of water maze, increased and decreased the retention scores in passive and active avoidance task, respectively. Administration of YC-1 30 min after foot-shock stimulation did not significantly affect retention scores in response to passive avoidance test. Administration of scopolamine, a muscarinic antagonist, markedly impaired the memory acquisition. Pretreatment of YC-1 inhibited the scopolamine-induced learning deficit. The enhancement of learning behaviour by YC-1 was antagonized by intracerebroventricular injection of NOS inhibitor L-NAME and PKG inhibitors of KT5823 and Rp-8-Br-PET-cGMPS, indicating that NO-cGMP-PKG pathway is also involved in the learning enhancement action of YC-1. YC-1 is thus a good drug candidate for the improvement of learning and memory. [source] Inhibition by Lipopolysaccharide of Naloxone-Induced Luteinising Hormone Secretion Is Accompanied by Increases in Corticotropin-Releasing Factor Immunoreactivity in Hypothalamic Paraventricular Neurones in Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2005D. He Abstract We have recently reported that lipopolysaccharide (LPS), a bacterial endotoxin, inhibits steroid-induced as well as naloxone-induced luteinising hormone (LH) secretion in ovariectomised oestrogen-primed rats. In the present study, we examined whether corticotropin-releasing factor (CRF) may be involved in the LPS-induced inhibition of LH secretion. Unanaesthetised rats were treated with an intravenous (i.v.) injection of LPS (10 µg) or saline, followed by an i.v. injection of naloxone (20 mg/kg). After sequential blood samples were collected for determination of serum LH concentrations, the brains were fixed and CRF-immunoreactivity was examined histochemically. In control rats receiving saline injections, only a small number of CRF-immunoreactive (ir) cells were found in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), and naloxone significantly increased serum LH concentrations within 10 min. By contrast, in LPS-treated rats, the number of CRF-ir cells was significantly greater than that in control rats, and the effect of naloxone was completely abolished. In a separate experiment, an intracerebroventricular injection of 5 µg CRF inhibited naloxone-induced LH release, mimicking the effect of LPS. These results suggest that LPS stimulates production of CRF in PVN neurones, which in turn inhibits LH secretion without opioidergic mediation. [source] Methodology for the study of the hypothalamic-pituitary hormone secretion in cattleANIMAL SCIENCE JOURNAL, Issue 1 2009Tsutomu HASHIZUME ABSTRACT Studies on the neuroregulatory mechanisms on the secretion of anterior pituitary (AP) hormones in domestic animals are important because nearly all complex physiological and metabolic processes are regulated by the AP hormones. To examine them, this article considers in vivo approaches such as the techniques of intrahypothalamic injection, intracerebroventricular injection, push-pull perfusion, and microdialysis, which have been employed in our own research group for the study in cattle. Also, in vitro approaches such as bovine AP cell culture and the AP explants superfusion system are described. This article clarifies the potential of neuroendocrine study techniques in cattle. [source] Excitotoxicity-induced endocytosis confers drug targeting in cerebral ischemia,ANNALS OF NEUROLOGY, Issue 3 2009Anne Vaslin MSc Objective Targeting neuroprotectants specifically to the cells that need them is a major goal in biomedical research. Many peptidic protectants contain an active sequence linked to a carrier such as the transactivator of transcription (TAT) transduction sequence, and here we test the hypothesis that TAT-linked peptides are selectively endocytosed into neurons stressed by excitotoxicity and focal cerebral ischemia. Methods In vivo experiments involved intracerebroventricular injection of TAT peptides or conventional tracers (peroxidase, fluorescein isothiocyanate-dextran) in young rats exposed to occlusion of the middle cerebral artery at postnatal day 12. Cellular mechanisms of uptake were analyzed in dissociated cortical neuronal cultures. Results In both models, all tracers were taken up selectively into stressed neurons by endocytosis. In the in vivo model, this was neuron specific and limited to the ischemic area, where the neurons displayed enhanced immunolabeling for early endosomal antigen-1 and clathrin. The highly efficient uptake of TAT peptides occurred by the same selective mechanism as for conventional tracers. All tracers were targeted to the nucleus and cytoplasm of neurons that appeared viable, although ultimately destined to die. In dissociated cortical neuronal cultures, an excitotoxic dose of N -methyl- D -aspartate induced a similar endocytosis. It was 100 times more efficient with TAT peptides than with dextran, because the former bound to heparan sulfate proteoglycans at the cell surface, but it depended on dynamin and clathrin in both cases. Interpretation Excitotoxicity-induced endocytosis is the main entry route for protective TAT peptides and targets selectively the neurons that need to be protected. Ann Neurol 2009;65:337,347 [source] KETANSERIN-INDUCED BAROREFLEX ENHANCEMENT IN SPONTANEOUSLY HYPERTENSIVE RATS DEPENDS ON CENTRAL 5-HT2A RECEPTORSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007Fu-Ming Shen SUMMARY 1Ketanserin may influence baroreflex function by blocking 5-HT2A receptors and/or ,1 -adrenoceptors through central and/or peripheral mechanisms. 2In the present study, we tested the hypothesis that the baroreflex sensitivity (BRS)-enhancing effects of ketanserin are mediated by central 5-HT2A receptors in spontaneously hypertensive rats (SHR). 3Using a conjugate of a monoclonal antibody to the serotonin reuptake transporter (SERT) and the toxin saporin (anti-SERT-SAP), which specifically eliminates the neurons that express SERT, the effects of ketanserin (0.3 and 3.0 mg/kg, i.g.) on BRS, blood pressure (BP), heart period (HP) and blood pressure variability (BPV) were compared between conscious intact SHR and SHR pretreated with anti-SERT-SAP. 4Immunochemistry showed that, 2 weeks after intracerebroventricular injection of the toxin, 5-HT expression was strikingly attenuated in the brain, whereas values of BRS, BPV and BP were similar to those in the sham group. In intact SHR, 0.3 mg/kg ketanserin significantly improved BRS (191% control) and reduced BPV without affecting BP; at 3.0 mg/kg, ketanserin significantly increased BRS (197% control) and decreased BPV and BP. In toxin-pretreated SHR, only the high dose of ketanserin improved BRS (132% control), neither of the ketanserin doses reduced BPV, but both significantly decreased BP. 5We conclude that the BRS-enhancing effects of ketanserin are mediated largely by central 5-HT2A receptors, whereas the antihypertensive effect of ketanserin persists even after destruction of serotonergic neurons in the central nervous system. [source] 5,7-dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slicesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Anja Birthelmer Abstract Adult rats were subjected to intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150 µg) and, 15 days later, to intrahippocampal grafts of fetal raphe cell suspensions. About 11 months later, we assessed baseline and electrically evoked release of tritium ([3H]) in hippocampal slices, preloaded with tritiated ([3H])choline or [3H]serotonin (5-HT), in the presence or absence of the 5-HT1B receptor agonist CP-93,129 and the 5-HT receptor antagonist methiothepine. HPLC determinations of monoamine concentrations were also performed. The lesions reduced the concentration of 5-HT (,90%) and the accumulation (,80%) as well as the evoked release (,90%) of [3H]5-HT. They also decreased the inhibitory effects of CP-93,129 on the evoked release of [3H]5-HT. Most interestingly, they facilitated the evoked release of [3H]acetylcholine (+20%). In slices from rats subjected to lesions and grafts, the responsiveness of the serotonergic autoreceptors (presumably located on the terminals of the grafted neurons) and the release of acetylcholine were close to normal. These results confirm that grafts rich in serotonergic neurons may partially compensate for the dramatic effects of 5,7-DHT lesions on serotonergic hippocampal functions. The lesion-induced reduction of the 5-HT1B autoreceptor-mediated inhibition of evoked 5-HT release may be an adaptation enhancing serotonergic transmission in the (few) remaining terminals. The facilitated release of acetylcholine is probably caused by a reduced serotonergic tone on the inhibitory 5-HT1B heteroreceptors of the cholinergic terminals. When related to data in the literature, this facilitation may be of particular interest in terms of transmitter-based strategies developed to tackle cognitive symptoms related to neurodegenerative diseases. [source] Postischemic treatment of neonatal cerebral ischemia should target autophagy,ANNALS OF NEUROLOGY, Issue 3 2009Julien Puyal PhD Objective To evaluate the contributions of autophagic, necrotic, and apoptotic cell death mechanisms after neonatal cerebral ischemia and hence define the most appropriate neuroprotective approach for postischemic therapy. Methods Rats were exposed to transient focal cerebral ischemia on postnatal day 12. Some rats were treated by postischemic administration of pan-caspase or autophagy inhibitors. The ischemic brain tissue was studied histologically, biochemically, and ultrastructurally for autophagic, apoptotic, and necrotic markers. Results Lysosomal and autophagic activities were increased in neurons in the ischemic area from 6 to 24 hours postinjury, as shown by immunohistochemistry against lysosomal-associated membrane protein 1 and cathepsin D, by acid phosphatase histochemistry, by increased expression of autophagosome-specific LC3-II and by punctate LC3 staining. Electron microscopy confirmed the presence of large autolysosomes and putative autophagosomes in neurons. The increases in lysosomal activity and autophagosome formation together demonstrate increased autophagy, which occurred mainly in the border of the lesion, suggesting its involvement in delayed cell death. We also provide evidence for necrosis near the center of the lesion and apoptotic-like cell death in its border, but in nonautophagic cells. Postischemic intracerebroventricular injections of autophagy inhibitor 3-methyladenine strongly reduced the lesion volume (by 46%) even when given >4 hours after the beginning of the ischemia, whereas pan-caspase inhibitors, carbobenzoxy-valyl-alanyl-aspartyl(OMe)-fluoromethylketone and quinoline-val-asp(OMe)-Ch2-O-phenoxy, provided no protection. Interpretation The prominence of autophagic neuronal death in the ischemic penumbra and the neuroprotective efficacy of postischemic autophagy inhibition indicate that autophagy should be a primary target in the treatment of neonatal cerebral ischemia. Ann Neurol 2009 [source] | |||||||||||||