Neck Location on the Outer Convexity is a Predictor of Incomplete Occlusion in Treatment with the Pipeline Embolization Device: Clinical and Angiographic Outcomes.

BACKGROUND AND PURPOSE: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up. MATERIALS AND METHODS: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle, <160°), inner convexity type (included angle, >200°), and lateral wall type (160° ≤ included angle ≤200°). This classification reflects the metal coverage rate and flow dynamics. RESULTS: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P = .001), aneurysms with the branching artery from the dome (OR, 10.56; P = .002), fusiform aneurysms (OR, 10.2; P = .009), and outer convexity-type saccular aneurysms (versus inner convexity type: OR, 30.3; P < .001; versus lateral wall type: OR, 9.71; P = .001) were independently associated with a higher rate of incomplete occlusion at the last follow-up. No permanent neurologic deficits or rupture were observed in the follow-up period. CONCLUSIONS: The aneurysm neck located on the outer convexity is a new, incomplete occlusion predictor, joining older age, fusiform aneurysms, and aneurysms with the branching artery from the dome. No permanent neurologic deficits or rupture was observed in the follow-up, even with incomplete occlusion.

Low expression of FGF1 (fibroblast growth factor-1) in rat parasympathetic preganglionic neurons.

Fibroblast growth factor-1 (FGF1), a member of the FGF family of growth factors, is localized in cholinergic neurons where it has trophic activity. We recently reported that cholinergic neurons in the dorsal motor nucleus of the vagus (DMNV) contain little FGF1, raising the possibility that FGF1 is not localized to parasympathetic preganglionic cholinergic neurons. To clarify this issue, we investigated the co-localization of FGF1 with cholinergic neuron markers in the Edinger-Westphal nucleus (EWN), salivatory nucleus, DMNV, and sacral parasympathetic nucleus by double immunofluorescence using antibodies to FGF1 and choline acetyltransferase (ChAT). The neurons in the EWN were devoid of FGF1. In the salivatory nucleus, 13% of ChAT-positive neurons were also positive for FGF1. In the DMNV, only 8% of ChAT-positive neurons contained FGF1, and in the sacral parasympathetic nucleus, 18% of ChAT-positive neurons were FGF1-positive. We also confirmed that a large number of ChAT-positive motor neurons in the oculomotor nucleus, facial nucleus, hypoglossal nucleus, and spinal motor neurons contained FGF1. The results confirmed that parasympathetic preganglionic neurons are largely devoid of FGF1, which is a unique feature among cholinergic neurons.

Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats.

Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.

Orexin-A (Hypocretin-1) and leptin enhance LTP in the dentate gyrus of rats in vivo.

Orexin-A (Hypocretin-1) has been localized in the posterior and lateral hypothalamic perifornical region. Orexin containing axon terminals have been found in hypothalamic nuclei and many other parts of the brain; for example, the hippocampus. Two types of orexin receptors have been discovered. Orexin 1 type of receptors have been described and been shown to be widely distributed in the rat brain including the hippocampus. Subsequently Orexin-A was found to impair both water maze performance and hippocampal long term potentiation (LTP). Leptin is expressed in adipose tissue and released into the blood where it affects food intake and can also produce widespread physiological changes mediated via autonomic preganglionic neurons, pituitary gland, and cerebral cortex. Immunoreactivity for leptin receptors has been found in various hypothalamic nuclei including the lateral hypothalamic area as well as the hippocampus especially in the dentate gyrus and CA1. Leptin receptor deficient rats and mice also show impaired LTP in CA1 and poor performance in the water maze. The present study was conducted to determine the effects of 0.0, 30, 60, 90, and 100 nM, orexin-A, and leptin, 0.0, 1.0, 100 nM, 1, and 10 microM, in 1.0 microl of ACSF, applied directly into the dentate gyrus, on LTP in medial perforant path dentate granule cell synapses in urethane anesthetized rats. Orexin-A specifically enhanced LTP at the 90 nM dose; and it was possible to block the enhancement by pretreating the animals with SB-334867, a specific orexin 1 receptor antagonist. Leptin enhanced normal LTP at 1.0 microM but inhibited LTP at lower and higher doses. These results and previous data indicate that the same peptide could possibly have different modulatory post synaptic effects in different hippocampal synapses dependent upon different types of post synaptic receptors.

Orexin-A (hypocretin-1) impairs Morris water maze performance and CA1-Schaffer collateral long-term potentiation in rats.

Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (hypocretin-1) and orexin-B (hypocretin-2) and send their axons to the hippocampus, which predominantly expresses orexin receptor 1 showing a higher sensitivity to orexin-A. The purpose of the present study was to assess the effects of orexin-A on the performance of Wistar rats during the Morris water maze test and then to determine the effects of orexin-A on both the long-term potentiation and long-term depression in Schaffer collateral/commissural-CA1 synapses in hippocampal slices. The results of the Morris water maze test show that 1.0 and 10 nmol of orexin-A, when administered intracerebroventricularly, retarded spatial learning. A probe test examined after training of water maze task also showed an impairment in spatial memory. The results of an electrophysiological study using hippocampal slices demonstrated that 1.0 to 30 nM of orexin-A applied to the perfusate produces a dose-dependent and time dependent suppression of the long-term potentiation. In addition, the long-term depression was not affected by orexin-A. The results of a paired-pulse facilitation experiment indicated that the effects of orexin-A were post-synaptic and not due to presynaptic transmitter release. These results show that orexin-A impairs spatial performance and these impairments can be attributed to a suppression of long-term potentiation in the Schaffer collateral-CA1 hippocampal synapses.

Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents.

Leptin is well known to be involved in the control of feeding, reproduction and neuroendocrine functions through its action on the hypothalamus. However, leptin receptors are found in brain regions other than the hypothalamus (including the hippocampus and cerebral cortex) suggesting extrahypothalamic functions. We investigated hippocampal long-term potentiation (LTP) and long-term depression (LTD), and the spatial-memory function in two leptin receptor-deficient rodents (Zucker rats and db/db mice). In brain slices, the CA1 hippocampal region of both strains showed impairments of LTP and LTD; leptin (10(-12) M) did not improve these impairments in either strain. These strains also showed lower basal levels of Ca(2+)/calmodulin-dependent protein kinase II activity in the CA1 region than the respective controls, and the levels did not respond to tetanic stimulation. These strains also showed impaired spatial memory in the Morris water-maze test (i.e. longer swim-path lengths during training sessions and less frequent crossings of the platform's original location in the probe test. From these results we suggest that the leptin receptor-deficient animals show impaired LTP in CA1 and poor spatial memory due, at least in part, to a deficiency in leptin receptors in the hippocampus.

2-buten-4-olide, an endogenous feeding suppressant, improves spatial performance through brain acidic fibroblast growth factor in mice.

Endogenous sugar acid 2-buten-4-olide, a satiety substance, has been shown to increase the blood glucose, norepinephrine, and glucocorticoid concentrations that are known to modulate learning and memory processes. The glucose-induced release of acidic fibroblast growth factor facilitated the hippocampus-dependent memory function. In the present study, we investigated the effect of 2-buten-4-olide on the spatial performance of male DDY mice undergoing the water maze task. The intraperitoneal injection of 2-buten-4-olide (5 mg/kg) facilitated the spatial performance, which was indicated by a reduction in the escape latency in which the mouse finds and climbs the goal platform in comparison to the vehicle-injected control mice. In the probe test after removing the platform, the 2-buten-4-olide-treated mice stayed a longer time in the quadrant where the platform was originally located and crossed more frequently at the platform location than did the control mice. The pretreatment of acidic fibroblast growth factor antibody injected into the lateral ventricle eliminated the effect of 2-buten-4-olide both during the training sessions and during the probe test. Therefore, 2-buten-4-olide was found to improve the spatial performance, and this effect is mediated, at least in part, by acidic fibroblast growth factor.

Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8.

Effects of leptin and orexin-A on food intake and feeding related hypothalamic neurons.

The lateral hypothalamic area (LHA) and the ventromedial hypothalamic nucleus (VMH) have historically been implicated in ingestive behavior, energy balance and body mass regulation. The LHA is more closely associated with the initiation of eating; whereas the VMH mediates the cessation of eating. The parvocellular part of the paraventricular nucleus (pPVN) is also included in the suppressing mechanism. Recently, two hypothalamic peptides, orexin-A and orexin-B, localized in the posterior and lateral hypothalamic perifornical region were discovered in the rat brain and they increase food intake. Leptin, a protein encoded by an obesity gene, expressed in adipose tissue and released into the blood also affects food intake. Orexin and leptin receptors have been localized in the LHA, pPVN, and VMH. The purpose of this study was to measure food intake in the rat in response to leptin and orexin-A; and to determine their electrophysiological effects on feeding related hypothalamic neurons. Results clearly show that leptin suppresses food intake whereas orexin-A increases food intake. These differences are associated with leptin and orexin-A modulatory effects on LHA, pPVN, and VMH glucose responding neurons. In the LHA, leptin inhibits a larger proportion of both glucose-sensitive neurons (GSNs) and non-GSNs. In the pPVN, leptin increases more GSNs in comparison to non-GSNs. Whereas in the VMH, leptin increases the activity of glucoreceptor neurons (GRNs) in comparison to non-GRNs. Orexin-A had opposite effects: increases activity of GSNs more than the non-GSNs in the LHA and significantly suppresses GRNs in the VMH. In the pPVN, orexin-A had no observable effects on neurons that have a low density of orexin 2 receptors. Results are discussed in terms of hypothalamic neural circuits that are sensitive to endogenous food intake inducing and reducing substances.

Leptin effects on feeding-related hypothalamic and peripheral neuronal activities in normal and obese rats.

We investigated the effects of leptin on central and/or peripheral feeding-related neuronal networks in Wistar male rats either normal (350-450 g) or Zucker obese (500-800 g). Low doses (1-10 pg) of leptin inhibited glucose-sensitive vagal hepatic afferent discharges and facilitated sympathetic efferent discharges to brown and white adipose tissue. Most (40-75%) neurons in the arcuate nucleus were significantly inhibited by superperfusion with leptin (0.1 nM-10 pM) under in vitro conditions. In anesthetized animals, leptin was applied electrophoretically to single hypothalamic neurons. Both glucose-sensitive neurons (GSNs) and non-GSNs in the feeding center (LHA) were significantly inhibited. Most glucoreceptor neurons in the satiety center (VMH) were significantly excited. Their depolarization was confirmed by activation of Na+ and K+ channels by 10(-11) M leptin using the perforate blind patch-clamp method. Although leptin excited GSNs in the parvocellular part of the paraventricular nucleus, the effects of leptin on such neuronal activity were slight or absent in Zucker obese rats. These results suggest that the feeding-suppression effects of leptin are mediated by its effects on signal transduction through both the central and the peripheral nervous systems.

Effects of an acidic fibroblast growth factor fragment analog on learning and memory and on medial septum cholinergic neurons in senescence-accelerated mice.

We examined the effects of repeated subcutaneous injections of an acidic fibroblast growth factor fragment analog, [Ala16] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One group of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala16] acidic fibroblast growth factor (1-29), whereas the other group of accelerated senescence-prone-8 mice and a group of accelerated senescence-resistant mice (control) received vehicle solution. Injections began at three weeks after birth and were given weekly for 10 months. In a passive avoidance test, the mean retention latency at three, six and nine months of age was significantly longer in controls (vehicle-treated accelerated senescence-resistant-1) and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than in vehicle-treated accelerated senescence-prone-8 mice, and the latency in acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice was significantly shorter than that in controls only at nine months of age. In the Morris water maze task, the mean latency to climb onto the platform was significantly longer in acidic fibroblast growth factor fragment- and vehicle-treated accelerated senescence-prone-8 mice than in controls. However, the mean latency in the third and fourth trial blocks was significantly shorter for acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than for vehicle-treated accelerated senescence-prone-8 mice. In the probe trials, controls and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice spent significantly more time in the quadrant in which the platform had previously been located than in the other three quadrants. In acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice, the density of medial septum neurons intensely stained for choline acetyltransferase was significantly greater than that in vehicle-treated accelerated senescence-prone-8 mice, but significantly less than that in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblast growth factor (1-29) on learning and memory function in accelerated senescence-prone-8 mice may be related to a preservation of function in medial septum cholinergic neurons.

Protective effect of acidic fibroblast growth factor against ischemia-induced learning and memory deficits in two tasks in gerbils.

The influence of transient forebrain ischemia on behavioral performance, and the effect of intracerebroventricular (i.c.v.) injection of acidic fibroblast growth factor (aFGF) on such ischemia-induced deficits were examined in Mongolian gerbils by assessing learning and memory in two tasks: passive avoidance and Morris water maze. A 5-min period of forebrain ischemia led to learning and memory deficits in both tasks, and also to neuronal death in the hippocampal CA1 region. Continuous i.c.v. infusion of aFGF bilaterally into the lateral ventricules by osmotic minipumps over 2 days before, and 5 days after the ischemia (a total of 3.6 microg/gerbil) largely prevented both the ischemia-induced behavioral deficits and the neuronal death in the hippocampus. These observations suggest that the hippocampus is a critical site for the performance of the two tasks, and that aFGF has a protective effect against such ischemia-induced learning and memory deficits in gerbils.

Increased expression of hippocampal cholinergic neurostimulating peptide-related components and their messenger RNAs in the hippocampus of aged senescence-accelerated mice.

Hippocampal cholinergic neurostimulating peptide stimulates cholinergic phenotype development by inducing choline acetyltransferase in the rat medial septal nucleus in vitro. Adult senescence-accelerated-prone mice/8, a substrain of the senescence-accelerated-prone mouse, show a remarkable age-accelerated deterioration in learning and memory. We cloned mouse hippocampal cholinergic neurostimulating peptide precursor protein complementary DNA. The deduced amino acid sequence showed that the neurostimulating peptide itself is the same as that found in the rat. In situ hybridization revealed that the highest expression of the precursor protein messenger RNA was in hippocampal pyramidal neurons. Compared with a strain of senescence-accelerated-resistant mouse (control mouse), adult senescence-accelerated-prone mice/8 showed increased expression of both the precursor messenger RNA and the neurostimulating peptide-related immunodeposits in the hippocampal CA1 field. The deposits were intensely and diffusely precipitated in neuropils throughout the strata oriens and radiatum in senescence-accelerated-prone mice/8, but not in control mice. The neurostimulating peptide content in the hippocampus was higher in senescence-accelerated-prone mice/8 than in control mice, while its precursor protein itself was not different between the two strains. Furthermore, our previous and present data show that the medial septal and hippocampal choline acetyltransferase activity was significantly lower in senescence-accelerated-prone mice/8 than in control mice. The data suggest that, in hippocampal neurons in adult senescence-accelerated-prone mice/8, the production of hippocampal cholinergic neurostimulating peptide precursor protein in neuronal somata, which is associated with an increased expression of its messenger RNA in the CA1 field, occurs as a consequence of low activity in their presynaptic cholinergic neurons. This is followed by accelerated processing to generate bioactive peptide and transport to its functional fields. However, certain mechanisms reduce the release of the peptide and lead to its accumulation in the neuropil. These disturbances of the septohippocampal cholinergic system might be the biochemical mechanism underlying the characteristic deterioration of senescence-accelerated-prone mice/8.

Induction of outward current by orexin-B in mouse peritoneal macrophages.

To define effects of novel feeding regulating peptides, orexins, in immunocompetent cells, ion channel activity in mouse peritoneal macrophages was analyzed by the perforated patch-clamp method. Orexin-B (OX-B) induced an outward current at smaller holding potentials than K+ equilibrium potentials. Reversal potentials of OX-B induced current were dependent on external K+ concentrations but not on external Cl- concentration. Orexin-A is less effective than OX-B. Quinine blocked the outward current and tetraethylammonium partially suppressed the current. These results suggest that OX-B can modulate macrophage functions through the activation of Ca2+-dependent K2+ channels.

Acidic fibroblast growth factor activates adrenomedullary secretion and sympathetic outflow in rats.

Effects of exogenous acidic fibroblast growth factor (aFGF), which is increased in the brain by food intake, on the plasma levels of catecholamines and on sympathetic efferent outflow were examined in anesthetized rats. A guide cannula was inserted into the cerebral third ventricle, and a vascular indwelling catheter was inserted into the right atrium from the jugular vein. Plasma epinephrine (Epi) and norepinephrine (NE) increased markedly in a dose-dependent manner for up to 120 min after intracerebroventricular or intravenous administration of aFGF (6-667 fmol/rat). Concomitant increases occurred in the efferent activity in the sympathetic nerves supplying the adrenal, spleen, and interscapular brown adipose tissue after the above administrations of aFGF. Both intravenous and intracerebroventricular administration of 10 ng basic FGF (bFGF) also increased sympathetic adrenal efferent activity and plasma Epi and NE concentrations. However, the increases induced by 10 ng bFGF were smaller than those induced by 10 ng aFGF. Bilateral splanchnicotomy completely prevented the increases in Epi induced by intracerebroventricular or intravenous aFGF but had less effect on the increases in NE. Pretreatment with an antibody against corticotropin-releasing factor (CRF), given via the intracerebroventricular route, significantly attenuated the increases in Epi and NE evoked by intracerebroventricular or intravenous administration of aFGF. Hepatic vagotomy also greatly reduced the increases in both catecholamines and the increases in sympathetic efferent firing rates evoked by intravenous administration of aFGF. These findings indicate that 1) aFGF administered intracerebroventricularly activates adrenomedullary secretion and sympathetic outflow via CRF release and 2) aFGF injected intravenously also induces sympathoadrenomedullary activation via centrally released CRF. The idea is discussed that sympathetic activation induced either by endogenous aFGF after feeding or by exogenously administered aFGF may play roles both in energy expenditure after overeating and in the modulation of immune functions.

Enhancement of phagocytosis in mouse peritoneal macrophages by fragments of acidic fibroblast growth factor (aFGF).

To characterize the effects of acidic fibroblast growth factor (aFGF) in mouse peritoneal macrophages, the effects of aFGF fragments on phagocytosis were examined. Fragments that were tested included aFGF(1-15), aFGF(1-20), aFGF(1-29), Ala16-aFGF(1-29), aFGF(9-29) and aFGF(114-140). aFGF(1-29) induced an enhancement of phagocytosis in a dose-dependent manner and was more effective than any other fragments tested. Even in Ca2+-and Mg2+-free solutions, phagocytosis was enhanced by aFGF(1-29). However, the enhancement induced by aFGF(1-29) was completely inhibited in the presence of mannan (4 mg/ml). Furthermore, the enhancement of phagocytosis by aFGF(1-29) was suppressed by heparin (100 microg/ml). The results of the present study suggest that the active region of aFGF that is responsible for the enhancement of phagocytosis corresponds to residues 15-29 and that phagocytosis, which is modulated by aFGF, is independent of extracellular Ca2+ and is mediated by mannose receptors.

A single pre-training glucose injection induces memory facilitation in rodents performing various tasks: contribution of acidic fibroblast growth factor.

Effects of a pre-training intraperitoneal glucose injection on learning and memory were tested using two tasks: passive avoidance and Morris water maze. In the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h prior) to a trial that combined acquisition with passive avoidance of foot shock showed a significantly increased retention latency when tested 24 h later. Thus, this effect was time-dependent, and it was also found to be dose-dependent by further experiment. In contrast, 2-deoxy-D-glucose and fructose had no such effect. In the Morris water maze task, glucose injection 2 or 3 h before a block of trials enhanced the spatial memory performance of mice. These glucose-induced memory-facilitation effects were abolished by an intracerebroventricular injection of anti-acidic fibroblast growth factor antibody 30 min before the glucose injection, suggesting a critical role for endogenous acidic fibroblast growth factor in this facilitatory effect. Furthermore, continuous intracerebroventricular infusion of acidic fibroblast growth factor in rats significantly increased retention latency (when tested repeatedly on successive days using a passive avoidance task). Our earlier studies demonstrated that brain acidic fibroblast growth factor is produced in the ependymal cells of the cerebroventricular system, and is released into the cerebrospinal fluid following either a meal or a (intraperitoneal or intracerebroventricular) glucose injection. This released acidic fibroblast growth factor also diffuses into the brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus, and elsewhere in the brain some 2 h after the meal or glucose injection. These and the present findings indicate (i) that pre-training glucose injection improves memory performance, and (ii) that acidic fibroblast growth factor, especially by its action within the hippocampus, is involved in this enhancement process.

Effect of acidic fibroblast growth factor (aFGF) on phagocytosis in mouse peritoneal macrophages.

The effects of acidic fibroblast growth factor (aFGF) on phagocytosis in peritoneal macrophages from thioglycollate-elicited mice were examined using flow cytometry. aFGF enhanced phagocytosis of fluorescein isothiocyanate-labeled latex particles in a dose-dependent manner. Basic fibroblast growth factor (bFGF) also enhanced phagocytosis. This study suggests that aFGF can modulate an important activity of macrophages.

Acidic fibroblast growth factor activates hypothalamic-pituitary-adrenocortical axis in rats.

Effects of acidic fibroblast growth factor (aFGF), an endogenous satiety substance, on the hypothalamic-pituitary-adrenocortical axis were examined under pentobarbital sodium anesthesia in rats. A guide cannula was inserted into the cerebral third ventricle and a vascular indwelling catheter was inserted into the right atrium from the jugular vein 2 wk and 3 days, respectively, before the experiment. A marked dose-dependent increase in plasma corticosterone was detected from 20 min to 2 h after intracerebroventricular administration of aFGF (1-10 ng). Significant increases in plasma adrenocorticotropic hormone (ACTH) were observed from 5 to 150 min after the intracerebroventricular administration of 10 ng aFGF. Significant dose-dependent increases in plasma corticosterone were also observed after intravenous injections of aFGF (1, 10, and 100 ng), together with increases in the plasma ACTH level. Pretreatment with antibody to corticotropin-releasing factor via the intracerebroventricular route abolished the increases in corticosterone induced by intracerebroventricularly administered aFGF, but not those induced by intravenous injection of aFGF. In adrenal glands perfused in situ with artificial medium, the corticosterone secretion rate increased slightly in response to 10(-9) M aFGF. These findings suggest that intracerebroventricular administration of aFGF activates the hypothalamic-pituitary-adrenal axis via corticotropin-releasing factor release in the brain, whereas peripheral administration of aFGF activates adrenocortical secretion mainly via a direct action on ACTH release.

Complex functional attributes of amygdaloid gustatory neurons in the rhesus monkey.

To reveal specific functions of glucose-sensitive (GS) and glucose-insensitive (GIS) cells in chemical information processing, single neuron activity was recorded in the amygdaloid body (AMY) of macaques during: 1) gustatory stimulations and 2) micro-electrophoretic administration of chemicals. Of the 629 neurons tested, 56 (8.9%) responded to, usually two or more, taste qualities. Hedonically distinct tastants usually elicited opposite firing rate changes of the gustatory cells. Seventy percent of the gustatory responses were recorded from GS neurons (17% of all AMY cells). Catecholamines (CAs) induced discharge rate changes in a majority of taste-responsive neurons: The GS gustatory cells were suppressed by norepinephrine (in the form of noradrenaline HCl, NA), whereas the GIS taste-responsive neurons were facilitated by dopamine (DA). Furthermore, NA- and/or DA-antagonists were able to attenuate or suppress taste-elicited responses of several of these cells. These and previous data indicate a specific functional organization of AMY gustatory cells: The GS and GIS taste neurons appear to be involved in differential integration of feeding-associated humoral-metabolic, motivational and exogenous chemical information.