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Functional antagonism of airway constriction in the canine lung periphery.

We studied the ability of a beta-adrenergic agonist (albuterol) to attenuate calcium chelator- and acetylcholine-induced airway constriction in the lung periphery of anesthetized mongrel and Basenji-Greyhound (BG) dogs. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA and acetylcholine. Time course of the response to Na2EDTA differed significantly between mongrel and BG dogs. Peak response to challenge with 4% Na2EDTA occurred within 2 min for mongrel dogs and at 5 min for BG dogs. Albuterol (1 microgram/kg iv) significantly attenuated Na2EDTA-induced bronchoconstriction in both groups of animals (P less than 0.01, each group). Albuterol (1 microgram/kg iv) significantly attenuated acetylcholine-induced bronchoconstriction in mongrel (P less than 0.01) but not in BG dogs. We conclude that a qualitative difference exists in the mechanism of Na2EDTA-induced constriction in the lung periphery of BG compared with mongrel dogs. In addition, the lung periphery of BG dogs demonstrates reduced beta-adrenergic sensitivity with respect to a cholinergic challenge compared with mongrels, suggesting enhanced cholinergic inhibition of the beta-adrenergic system.

Acetylcholine↗

Ultra-fast three-dimensional MR perfusion imaging of the entire brain in acute stroke assessment.

We sought to evaluate a three-dimensional (3D) whole-brain perfusion technique based on echo-shifting (PRESTO) for its performance in evaluation of acute stroke. Twenty-six patients were scanned within 6 hours after onset of hemispheric symptoms, and the results were compared with results of diffusion-weighted imaging (DWI) and digital subtraction angiography (DSA). The signal-to-noise ratio of the images was 61 +/- 3 pre-contrast and 47 +/- 3 at the bolus peak. Brain coverage on perfusion parameter maps was 95% +/- 2% compared with that displayed on T2-weighted images, with only minor artifacts related to susceptibility at the skull base. Measured regional cerebral blood volume (rCBV) reduction closely correlated to lesion size on initial DWI and to final clinical outcome (P = 0.006), consistent with results previously reported for 2D perfusion methods. Mismatches between DWI and perfusion imaging characterized the total extent of tissue at risk, and the contrast timing correlated with the amount of collateral circulation as shown on DSA. In conclusion, 3D imaging using the PRESTO technique permits high-quality perfusion imaging of the entire brain.

Adolescent↗

Transpupillary laser phototherapy of tumors and vascular anomalies of retina and choroid: theoretical approach and clinical implications.

BACKGROUND: Small retinal and choroidal tumors situated near the optic nerve or macula, such as retinoblastomas and malignant melanomas, as well as various other anomalies, in particular vascular malformations, may successfully be treated by photocoagulation. Model assumptions geared towards maximizing efficiency and minimizing undesirable side effects are forwarded, and the most important parameters subserving photothermal destruction, such as radiation field and thermal energy, analyzed. The influence exerted by physical traits of various tissues involved are also considered. METHODS: The model approximations presented are based on classical radiation and absorption laws, as well as on the scattering properties of the various tissues implicated, these being considered as a function of wavelength and their relevance to the photodestructive task at hand. Particular attention is paid to the rate processes and reaction kinetics of irradiated proteins. CONCLUSIONS: Radiation sources emitting in the near-infrared range of the electromagnetic spectrum, such as the diode (810 nm) and the cw Nd:YAG (1064 nm) lasers, are optimal for the treatment of tumors and large, voluminous entities (such as Hippel-Lindau angiomas), owing to the good tissue penetration properties of their light. Those emitting in the shorter wavelength range, such as the argon ion (488 and 514 nm) and first harmonic--mode Nd:YAG (532 nm) lasers, are not suitable for such tasks, but they are ideal for the destruction of fine sanguinous structures, within which their light is strongly absorbed but through which it penetrates poorly. For the treatment of large anomalous structures, a combined short/long wavelength--strategy should also be considered as a viable alternative. Such a "wavelength mixture" is emitted by the xenon high pressure lamp of the once renowned Meyer-Schwickerath light coagulator. The precision and safety of photothermal destruction methods depend, in the first approximation, upon the details of the pulse energy deposition (wavelength, pulse height and duration, pulse dynamics, mode composition, focussing), the choice of which is determined by the optical and thermal constants of the irradiated tissues. Higher pulse energies will, of course, be more effective in destroying neoplastic cells, but the risk of producing undesired collateral heat damage will also increase concomitantly. Until we can ascertain the physical properties of the pathological tissues treated with certainty, we will hardly be able to achieve more than an approximation of an ideal treatment strategy. But with increasing developments in in vivo-diagnostic techniques, we expect that this goal will be attainable in the not too distant future.

Animals↗

Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity.

A number of vascular therapies could benefit from advanced methods for presentation of angiogenic growth factors, including growth of endothelium on small caliber vascular grafts and revascularization of ischemic tissue through induction of collateral vessels and microvessels. To explore methods to optimize the presentation and release of angiogenic factors in such applications in device integration and tissue repair, we studied three variant forms of vascular endothelial growth factor 121 (VEGF121), each with differential susceptibility to local cellular proteolytic activity, formulated within fibrin matrices. (1) The prototypic variant alpha2PI(1-8)-VEGF121 remains immobilized in fibrin matrices until its liberation by cell-associated enzymes, such as plasmin, that degrade the fibrin network [slow, cell-demanded release; J. Control. Release 72 (2001) 101-113]; the alpha2PI(1-8) domain serves as a site for covalent attachment to fibrin during coagulation. (2) We created a new VEGF variant, alpha2PI(1-8)-Pla-VEGF121 that couples to fibrin via a plasmin-sensitive sequence (Pla). Cleavage of this target site by plasmin enables direct release of alpha2PI(1-8)-Pla-VEGF121 from bulk matrix degradation (accelerated, cell-demanded release). (3) Native VEGF121 (burst, passive release) was considered as a reference. VEGF release profiles were determined experimentally as well as mathematically, alpha2PI(1-8)-Pla-VEGF121 being released ca. fourfold more quickly than alpha2PI(1-8)-VEGF121, both being retained compared to native VEGF121; the differences in release could be accounted for based on knowledge of the plasmin sensitivity of the bound growth factor and the structure of the fibrin network. The bound factors were competent in inducing endothelial cell proliferation, the matrix-bound forms being more effective than native VEGF121; as well as competent in inducing endothelial progenitor cell maturation into endothelial cells. These matrix-bound variants of VEGF121 may be particularly useful where retention in locally applied surgical sites is desired, such as prevention of washout from vascular graft coatings and slowing loss from tissue ingrowth matrices used in local tissue revascularization and repair.

Cell Proliferation↗

Postnatal development of muscarinic autoreceptors modulating acetylcholine release in the septohippocampal cholinergic system. II. Cell body region: septum.

We studied the postnatal development of the release of acetylcholine (ACh) and of presynaptic, release-inhibiting muscarinic autoreceptors in the cell body region of the septohippocampal cholinergic pathway. To this end, septal slices (350 microns thick) from rats of various postnatal ages (postnatal day 3 [P3] to P16) were preincubated with [3H]choline and stimulated twice (S1, S2: 360 pulses, 2 ms, 3 Hz, 60 mA) during superfusion with physiological buffer containing hemicholinium-3 (10 microM). In parallel, the activities of hemicholinium-sensitive high-affinity choline uptake (HACU, in synaptosomes) and of choline acetyltransferase (ChAT, in crude homogenates) were determined as markers for the development of cholinergic functions. In septal slices preincubated with [3H]choline, the electrically evoked overflow of 3H at S1 increased from 0.31% (P3) to 2.10% of tissue 3H (P16), the latter value being still lower than that of septal slices from adult rats (3.46% of tissue 3H). Already at P3, the evoked overflow of 3H was Ca(2+)-dependent and sensitive to tetrodotoxin, indicating an action potential-evoked exocytotic mechanism of ACh release early after birth. Presence of the muscarinic agonist oxotremorine (1 microM) significantly inhibited the evoked ACh release in septal slices beginning from P5: no significant effect was detectable at P3. The ACh esterase inhibitor physostigmine (1 microM) exhibited significant inhibitory effects from P13 onwards. The muscarinic antagonist atropine (1 microM) enhanced the evoked ACh release only in septal tissue from adult rats. The specific activities of HACU, or ChAT showed a 2- or 8-fold increase, respectively, from P3 to P16. In conclusion, presynaptic cholinergic functions seem to develop almost in parallel both in the cell body and the target area of the septohippocampal projection: also in the septal region nerve terminals on axon collaterals are endowed very early (at least at P3) with the apparatus for action potential-induced, exocytotic release of ACh. In contrast, the appearance of feedback inhibition via presynaptic muscarinic autoreceptors is delayed. Autoinhibition due to endogenously released ACh can be detected only later, most probably when endogenous ACh concentrations in the septal nuclei have reached a threshold value.

Acetylcholine↗

Effect of castration and testosterone administration on the neuromuscular junction in the levator ani muscle of the rat.

The ultrastructure of the neuromuscular junction (n.m.j.) of the androgen-sensitive levator ani muscle was studied in normal adult male rats, in 8-month-old rats castrated at the age of one month and in castrated rats treated with testosterone propionate (TP). Castration does not result in significant changes of the n.m.j. The density of synaptic vesicles and the postsynaptic junctional folds remain practically normal inspite of marked atrophy of the muscle. TP administration for 7 days results in marked changes in pre- and postsynaptic structures. There is slow progressive depletion of synaptic vesicles, appearance of cisternae and coated vesicles in axon terminals, and coalescence of coated vesicles with the plasma membrane. Coated vesicles are also found inside Schwann cells and among junctional folds. Dense core vesicles appear both in the axon terminals and in the postsynaptic area. Collateral sprouting of terminal axons with the formation of new immature junctions is observed. After 35 days of TP administration depletion of synaptic vesicles continues. Glycogen beta-particles, mostly freely dispersed, occasionally seen in axon terminals 7 days after TP administration, subsequently increase in number. In the endplate zone of the muscle fibre increased protein synthesis is indicated by a rapid increase in ribosomes and irregularly located myofilaments and myofibrils. The appearance of n.m.j. after testosterone administration resembles that described after nerve stimulation; the degree of change is however less pronounced.

Animals↗

Diffuse hemangioma of the rectum detected on multi-slice CT in an 18-year-old woman with Klippel-Trenaunay syndrome.

The paper reports a rare case of an 18-year-old woman with Klippel-Trenaunay syndrome, whose multi-phase multi-slice CT revealed diffuse colorectal hemangioma. The patient presented symptoms of consumption coagulopathy (Kasabach-Meritt syndrome) and intense collateral circulation in the course of portal hypertension. The CT lesions and possibilities of multiformat and 3D volume rendering reconstructions are presented. To our knowledge, this is the first report of diffuse hemangioma of the colon and rectum in a patient with KTS detected with multi-slice CT.

Adolescent↗

Vasopressin-sensitive neurons in the lateral paraventricular nucleus area in a guinea pig slice preparation.

The effects of vasopressin (VP) on hypothalamic neurons located in the region of the paraventricular nucleus (PVN) were analyzed using intracellular techniques in slices of guinea pig brains. Two different classes of neurons were electrophysiologically identified in the magnocellular lateral part of the PVN and in the adjacent area. In the former area, vasopressinergic neurons were identified according to their phasic activity and their endogenous properties. These neurons were not responsive to VP, applied through the perfusion medium or locally by pressure. On the other hand, nonmagnocellular neurons exhibiting low-threshold Ca2+ spikes (LTS) were recorded in the area adjacent to the lateral part of the PVN. LTS were deinactivated at hyperpolarized membrane levels and induced short bursts of action potentials. On these neurons, VP evoked depolarizations accompanied by increases in firing, without modification of membrane resistance. VP effects were not blocked by TTX, suggesting a postsynaptic action of the peptide. These data indicate that VP controls the firing pattern of LTS neurons and suggest that this action may involve collaterals of axons originating from neighbouring vasopressinergic neurons.

Action Potentials↗

The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine induces a novel form of depotentiation in the CA1 region of the hippocampus.

The ability of activation of group I metabotropic glutamate receptor (mGluR) to induce depotentiation was investigated at Schaffer collateral-CA1 synapses of rat hippocampal slices. Brief bath application (5 min) of group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) (10 microm) induced a long-term depression of synaptic transmission or depotentiation (DEP) of previously established long-term potentiation (LTP), which was independent of NMDA or A(1) adenosine receptor activation. This DHPG-DEP was observed when DHPG was delivered 3 min after LTP induction. However, when DHPG was applied at 10 or 30 min after LTP induction, significantly less depotentiation was found. DHPG-DEP (1) is reversible and has the ability to unsaturate LTP, (2) is synapse specific, (3) does not require concurrent synaptic stimulation, (4) is mechanistically distinct from NMDA receptor-dependent depotentiation, (5) requires mGluR5 activation, (6) requires rapamycin-sensitive mRNA translation signaling, (7) does not require phospholipase C or protein phosphatase activation, and (8) is not associated with a change in paired-pulse (PP) facilitation. In addition, the ability of DHPG to reverse LTP was mimicked by a long train of low-frequency (1 Hz/15 min) PP stimulation. Moreover, the expression of DHPG-DEP is associated with a reduction in the increase of the surface expression of AMPA receptors seen with LTP. These results suggest that the activation of mGluR5 and in turn the triggering of a protein synthesis-dependent internalization of synaptic AMPA receptors may contribute to the DHPG-DEP in the CA1 region of the hippocampus.

Animals↗

Simple detection of occluded coronary artery using retrograde flow in septal branch and left anterior descending coronary artery by transthoracic Doppler echocardiography at rest.

BACKGROUND: We hypothesized that coronary flow assessment by transthoracic Doppler echocardiography (TTDE) for both intramyocardial collateral channel and epicardial channels would be useful for identifying occluded left anterior descending coronary artery (LAD). METHODS: We assessed flow direction in the LAD and the septal branch (SEP) by TTDE in 302 consecutive patients who were suggested to have ischemic heart disease. We defined antegrade LAD flow as a direction from the base to the apex of the left ventricle in the anterior groove area, and antegrade SEP flow as a direction from anterior to inferior in the anterior interventricular septum. By contrast, we defined retrograde LAD and SEP flow as an inverse direction. We performed angiography on all patients. RESULTS: Retrograde flow was detected in 22 (LAD, 16 patients; SEP, 6 patients) of 23 patients with occluded LAD, and antegrade flow was detected in all patients without occluded LAD. The sensitivity and specificity for identification of occluded LAD by TTDE were 96% and 100%, respectively. CONCLUSIONS: Assessment of flow direction in both LAD and SEP by TTDE is a useful method in identification of occluded LAD.

Aged↗

Effects of pretreatment with a xanthine oxidase inhibitor on free radical levels during carotid endarterectomy.

OBJECTIVE: Free radicals contribute to the tissue damage caused by ischaemia-reperfusion. The aim of the present study was to investigate whether preoperative antioxidant therapy (allopurinol) affects free radical levels in cerebral venous blood in connection with surgery for carotid artery stenosis. MATERIALS AND METHODS: Twenty-five patients were randomised into the study. Thirteen were controls and 12 were pretreated with allopurinol the day before surgery. Before, during and after surgery, blood samples were drawn from the ipsilateral jugular vein. Radical levels were measured using the spin trap technique ex vivo using OXANOH as the spin trap. Multivariate statistics were used with Principal Component Analysis and Partial Least Square regression analysis. RESULTS: Radical levels increased with diabetes, high leukocyte count, high creatinine and a high degree of contralateral stenosis. Radical levels decreased with high age, blood pressure, collateral circulation as well as operation for left-side carotid artery stenosis. After pretreatment with allopurinol, several of the relationships noted in the control group were eliminated, i.e. leukocyte count, side of operation, Betapred pretreatment and collateral circulation. CONCLUSIONS: Radical levels can be determined in connection with surgery for carotid artery stenosis using an ex vivo spin trap method. With preoperative antioxidant therapy the relationships between enhanced radical levels and clinical data, as seen in control subjects, disappeared. This might indicate a beneficial effect of preoperative pretreatment with antioxidants.

Aged↗

Temporal and spatial constraints on the collateral sprouting of low-threshold mechanosensory nerves in the skin of rats.

We have studied the collateral sprouting of intact low-threshold mechanosensory nerves into adjacent denervated skin in rats. An "isolated" field was produced by extensive denervations of the surrounding skin; sprouting of the remaining cutaneous nerve supplying the field was looked for in the form of field expansion into the surrounding denervated territory at various postoperative intervals. Such isolated fields failed to expand in the adult rat for periods up to at least 85 days. "Nonfunctional" sprouting is unlikely to explain this failure. However, similar experiments done in very young animals gave a different result. In rat pups aged less than 20 days, isolated fields did expand, but this ceased at about 20 days, and attempts to evoke it after this time were unsuccessful. There seems to be a critical period for sprouting of these touch-sensitive nerves into denervated skin, and our evidence suggests that it may not begin until about 15 days of age. Within this developmental window the sprouting that occurs is spatially constrained, an isolated field expanding preferentially into denervated skin of the parent dermatome; if only skin of neighboring dermatomes is available there is no expansion. In contrast, low-threshold nerves regenerated readily after a crush at all ages studied, and the mechanosensory fields established by regenerating nerves expanded progressively into denervated skin without apparent constraints at dermatomal boundaries. The temporal and spatial constraints found for the sprouting of intact low-threshold axons are in marked contrast to their absence for the well-described sprouting of high-threshold (nociceptive) nerves.

Age Factors↗

The GABAergic projection of the dentate gyrus to hippocampal area CA3 of the rat: pre- and postsynaptic actions after seizures.

The glutamatergic granule cells of the dentate gyrus transiently express GABAergic markers after seizures. Here we show that when this occurs, their activation produces (i) GABA(A) receptor-mediated synaptic field responses in CA3, with the physiological and pharmacological characteristics of mossy fibre transmission, and (ii) GABA(A) receptor-mediated collateral inhibition. Control hippocampal slices present, on stimulation of the dentate gyrus, population responses in stratum lucidum, which are blocked by ionotropic glutamate receptor antagonists. By contrast, in slices from rats subjected to seizures in vivo, dentate activation additionally produces GABA(A) receptor-mediated field synaptic responses in the presence of glutamate receptor antagonists. One-dimensional current source density analysis confirmed the spatial coincidence of the glutamatergic and GABAergic dendritic currents. The GABA(A) receptor-mediated field responses show frequency-dependent facilitation and strong inhibition during activation of metabotropic glutamate receptors. In the presence of glutamate receptor blockers, a conditioning pulse delivered to one site of the dentate gyrus inhibits the population synaptic response and the afferent volley provoked by the activation of a second site, in a bicuculline-sensitive manner. In accordance with this, antidromic responses evoked by mossy fibre activation were enhanced by perfusion of bicuculline. Our results suggest that, for GABA receptor-dependent field potentials to be detected, a considerable number of boutons of a well-defined GABAergic pathway should simultaneously release GABA to act on a large number of receptors. Therefore, putative GABA release from the mossy fibres acts on pre- and postsynaptic sites to affect hippocampal activity at the network level after seizures.

Animals↗

Evolution of the Purkinje cell response to injury and regenerative potential during postnatal development of the rat cerebellum.

To understand the mechanisms leading to the progressive loss of intrinsic neuronal growth properties during central nervous system development, we have investigated the evolution of the response to injury and regenerative potential of immature Purkinje cells, axotomized at different postnatal ages from postnatal day (P)3 to P12. In adult rodents, these neurons are characterised by a weak cell body response to axotomy, which is associated with a remarkable resistance to injury and a poor regenerative capability. During the first postnatal week, Purkinje cells are strongly sensitive to injury and massively degenerate within a few days. Immature Purkinje cells react to neurite transection by a strong upregulation of c-Jun, accompanied by a moderate, but consistent, expression of the growth-associated protein (GAP)-43. In contrast, nicotinamide adenine dinucleotide monophosphate (NADPH)-diaphorase reactivity, which can be activated by adult Purkinje neurons, is not modified in their juvenile counterparts. The severed Purkinje axons show a vigorous regenerative sprouting both into the lesioned cerebellar environment and into embryonic neocortical tissue transplanted into the injury site. The typical adult features of the response to injury progressively develop during the second postnatal week, when the injured neurons acquire resistance, cell body changes become milder, the regenerative potential declines, and the severed axons undergo characteristic morphological modifications, including torpedoes and the hypertrophy of recurrent collateral branches. This complete reversal of the features and the outcome of the Purkinje cell reaction to axotomy likely results from the profound changes that occur in the maturing Purkinje cells and/or in their microenvironment during this phase of cerebellar development.

Animals↗

Effects of atropine on hippocampal theta cells and complex-spike cells.

The medial septal nuclei are essential for the naturally occurring hippocampal theta rhythm. Evidence that the rhythmic activity of the septum is carried via cholinergic afferents to the hippocampus has been: (a) the existence of a cholinergic septo-hippocampal projection, and (b) the sensitivity of one type of theta rhythm to antimuscarinic agents or cholinergic depletion. The muscarinic action of acetylcholine on pyramidal cells, however, is too slow to carry even a 4 Hz signal. Recent in vitro studies have confirmed a fast excitatory response by some hippocampal interneurons to muscarinic agonists. In urethane anesthetized rats, iontophoretic application of atropine to 17 hippocampal theta cells (presumed interneurons) during the theta rhythm, reduced their firing rates to an average of 24% of control rates. The effect of iontophoretic atropine application to 4 CA1 complex-spike cells (presumed pyramidal cells) was a selective elimination of their bursting activity with no significant effect on overall firing rate. The data suggest that: (1) interneuronal firing, during the hippocampal theta rhythm, is dominated by an excitatory cholinergic input and not by excitatory collaterals of pyramidal cells; and (2) somatic burst firing by CA1 pyramidal cells requires the presence of acetylcholine.

Acetylcholine↗

Induction of anti-allo-class I H-2 tolerance by inactivation of CD8+ helper T cells, and reversal of tolerance through introduction of third-party helper T cells.

The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells resulted in the abrogation of CD8+ T cell-mediated anti-bm1 (proliferative and interleukin 2-producing) T helper (Th) cell activities. In vitro stimulation of lymphoid cells from these mice with bm1 cells, however, generated a reduced, but appreciable, anti-bm1 cytotoxic T lymphocyte (CTL) response. Moreover, the anti-bm1 CTL response, upon stimulation with [bm1 x B6-C-H-2bm12 (bm12)]F1 spleen cells, was enhanced when compared with the response induced upon stimulation with bm1 cells. These in vitro results were reflected on in vivo graft rejection responses; bm1 skin grafts engrafted in the bm1-presensitized B6 mice exhibited prolonged survival, whereas (bm1 x bm12)F1 grafts placed collateral to bm1 grafts (dual engrafted mice) inhibited the tolerance to bm1. In the B6 mice 1-2 d after rejecting the bm1 grafts, anti-bm1 Th activities remained marginal, whereas potent anti-bm1 CTL responses were found to be generated from their spleen cells. Administration in vivo of anti-CD4 antibody into bm1-presensitized, dual graft-engrafted mice prolonged bm1 graft survival and interfered with enhanced induction of anti-bm1 CTL activity. These results indicate that anti-class I alloantigen (bm1) tolerance as induced by intravenous presensitization with the relevant antigens is not ascribed to the elimination of CD8+ CTL precursors, but to the specific inactivation of CD8+ Th cells, whose function can be bypassed by activating third-party Th cells.

Animals↗

Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs.

1. A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2. The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect. 3. Beraprost (1 microgram kg-1 min-1 i.v., infused for 15 min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1 microgram kg-1 min-1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP-induced platelet aggregation was as potent as that of the higher dose. 4. The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5. Post-ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6. The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti-aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclin-like cytoprotective effect through membrane stabilization.

Animals↗

Intrinsic and thalamic excitatory inputs onto songbird LMAN neurons differ in their pharmacological and temporal properties.

In passerine songbirds, the lateral portion of the magnocellular nucleus of the anterior neostriatum (LMAN) plays a vital role in song learning, possibly by encoding sensory information and providing sensory feedback to the vocal motor system. Consistent with this, LMAN neurons are auditory, and, as learning progresses, they evolve from a broadly tuned initial state to a state of strong preference for the bird's own song and acute sensitivity to the temporal order of this song. Moreover, normal synaptic activity in LMAN is required during sensory learning for accurate tutor song copying to occur (). To explore cellular and synaptic properties of LMAN that may contribute to this crucial stage of song acquisition, we developed an acute slice preparation of LMAN from zebra finches in the early stages of sensory learning (18-25 days posthatch). We used this preparation to examine intrinsic neuronal properties of LMAN neurons at this stage and to identify two independent excitatory inputs to these neurons and compare each input's pharmacology and short-term synaptic plasticity. LMAN neurons had immature passive membrane properties, well-developed spiking behavior, and received excitatory input from two sources: afferents from the medial portion of the dorsolateral thalamus (DLM), and recurrent axon collaterals from LMAN itself ("intrinsic" input). These two inputs differed in both their pharmacology and temporal properties. Both inputs were glutamatergic, but LMAN responses to intrinsic inputs exhibited a larger N-methyl--aspartate component than responses to DLM inputs. Both inputs elicited temporal summation in response to pairs of stimuli delivered at short intervals, but -2-amino-5-phosphonovalerate (APV) significantly reduced the temporal summation only of the responses to intrinsic inputs. Moreover, responses to DLM inputs showed consistent paired-pulse depression, whereas the responses to intrinsic inputs did not. The differences between these two inputs suggest that intrinsic circuitry plays an important role in transforming DLM input patterns into the appropriate LMAN output patterns, as has been suggested for mammalian thalamocortical networks. Moreover, in LMAN, such interactions may contribute to the profound temporal and spectral selectivity that these neurons will acquire during learning.

2-Amino-5-phosphonovalerate↗