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PubMed2003

[Arterial microcirculation in the optic chiasm, optic tracts and lateral geniculate bodies].

OBJECTIVES: The purpose of this study was to point out the microscopic vessels in the optic chiasm, optic tracts and lateral geniculate bodies. MATERIAL AND METHODS: This study was carried out on 20 brains, fixed in formaldehyde 10% and dissected under the surgical microscope. The material was summated to histological techniques on paraffin and performed on routine coloration. RESULTS: The lateral borders of the optic chiasm have more perforant branches as the median zone. The anterior and posterior segments of the optic tracts are rich in capillary vessels. The arteriolar branches penetrate into the lateral geniculate body on his inferior surface and borders. CONCLUSIONS: The knowledge of the arteriolar distribution in this segments of the optic pathways can explain the visual defects in some neuroophthalmologic syndromes.

Arterioles↗
PubMed2001

Multiple modes of calcium-induced calcium release in sympathetic neurons I: attenuation of endoplasmic reticulum Ca2+ accumulation at low [Ca2+](i) during weak depolarization.

Many cells express ryanodine receptors (RyRs) whose activation is thought to amplify depolarization-evoked elevations in cytoplasmic Ca2+ concentration [Ca2+](i) through a process of Ca2+ -induced Ca2+ release (CICR). In neurons, it is usually assumed that CICR triggers net Ca2+ release from an ER Ca2+ store. However, since net ER Ca 2+ transport depends on the relative rates of Ca2+ uptake and release via distinct pathways, weak activation of a CICR pathway during periods of ER Ca accumulation would have a totally different effect: attenuation of Ca2+ accumulation. Stronger CICR activation at higher [Ca2+](i) could further attenuate Ca2+ accumulation or trigger net Ca2+ release, depending on the quantitative properties of the underlying Ca2+ transporters. This and the companion study (Hongpaisan, J., N.B. Pivovarova, S.L. Colgrove, R.D. Leapman, and D.D. Friel, and S.B. Andrews. 2001. J. Gen. Physiol. 118:101-112) investigate which of these CICR "modes" operate during depolarization-induced Ca2+ entry in sympathetic neurons. The present study focuses on small [Ca2+](i) elevations (less than approximately 350 nM) evoked by weak depolarization. The following two approaches were used: (1) Ca2+ fluxes were estimated from simultaneous measurements of [Ca2+](i) and I(Ca) in fura-2-loaded cells (perforated patch conditions), and (2) total ER Ca concentrations ([Ca](ER)) were measured using X-ray microanalysis. Flux analysis revealed triggered net Ca2+ release during depolarization in the presence but not the absence of caffeine, and [Ca2+](i) responses were accelerated by SERCA inhibitors, implicating ER Ca2+ accumulation, which was confirmed by direct [Ca](ER) measurements. Ryanodine abolished caffeine-induced CICR and enhanced depolarization-induced ER Ca2+ accumulation, indicating that activation of the CICR pathway normally attenuates ER Ca2+ accumulation, which is a novel mechanism for accelerating evoked [Ca2+](i) responses. Theory shows how such a low gain mode of CICR can operate during weak stimulation and switch to net Ca2+ release at high [Ca2+](i), a transition demonstrated in the companion study. These results emphasize the importance of the relative rates of Ca2+ uptake and release in defining ER contributions to depolarization-induced Ca2+ signals.

Animals↗
PubMed1996

Entorhinal axons perforate hippocampal field CA3 in organotypic slice culture.

In growing towards their hippocampal targets, incoming afferent axons from the entorhinal cortex arrive at the subicular pole of the hippocampus and normally turn pialwards from the alvear path, crossing (perforating) the subiculum and field CA1, but never the more distally situated field CA3. To address the question of whether a specific repulsive characteristic of field CA3 might explain this behaviour, artificial confrontation were set up in vitro. Embryonic entorhinal explants were placed in restricted contact with 8-day-old rat hippocampal slices, orientated so that outgrowing axons could only grow into either the dentate gyrus, the subiculum/field CA1, or field CA3. Anterograde biotin-dextran labelling of projections after 2 weeks in culture showed that entorhinal axons perforated the stratum oriens, pyramidal cell layer, and stratum radiatum of CA3 just as readily as they did along their normal trajectory across CA1/subiculum. It is therefore concluded that spatiotemporal cues are more likely than specific chemorepulsive molecules to be involved in setting up this part of the entorhinal pathway.

Animals↗
PubMed1987

A posterior arthroscopic approach to bullet extraction from the hip.

A 22-year-old male sustained a gunshot injury to the left hip region. The bullet lodged in the articular surface of the femoral head posterosuperomedially. The location of the bullet within the hip joint stimulated the performance of an arthroscopy of the hip through a posterior approach. The authors are unaware of any other report in the literature describing such an approach. To minimize the dangers, a limited posterior incision was made and deepened through the short rotators. The arthroscope was introduced through the incision to perforate the posteroinferior portion of the hip joint capsule. The bullet was easily visualized with a 70 degree arthroscope. Positioning at the joint and traction are vital components to visualization. The use of three-dimensional CT scanning is an aid to the graphic understanding of the bullet's pathway and relations to the surfaces of the hip joint.

Adult↗
PubMed2006

Effects of mild induced hypothermia during experimental sepsis.

OBJECTIVES: The potential advantages of lowering core temperature during sepsis are to lower energy requirement and to activate various cell-protecting pathways. We experimentally investigated whether postconditioning temperature modifications influence survival duration during experimental sepsis. DESIGN: A prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Eighteen male Sprague-Dawley rats (median 326 g, range 310-347 g). INTERVENTIONS: After anesthesia, experimental sepsis was induced by cecal ligation and perforation. The animals were subsequently assigned a core temperature range: normothermia (37 degrees C), hyperthermia (42 degrees C), and mild hypothermia (32 degrees C). Anesthesia and analgesia were continuously maintained until death. MEASUREMENTS AND MAIN RESULTS: Plasma lactate and pyruvate concentrations were measured at sepsis induction (H0), 4 hrs later (H4), and/or at the time of death. A significant increase in lactate concentration was observed at the time of death in the 42 degrees C group (p = .04). Lactate-to-pyruvate ratio increased in the 32 degrees C (at H4) and 42 degrees C (at the time of death) groups (p = .04). A linear correlation between a longer survival duration and a lower assigned core temperature was observed (from 61 +/- 10 mins at 42 degrees C to 289 +/- 17 mins at 37 degrees C and to 533 +/- 69 mins at 32 degrees C; R = .959, p < .0001). CONCLUSIONS: The current results demonstrate that postconditioning hypothermia was associated with increased survival duration during experimental sepsis. Whether the observed benefits on survival duration are due to potential impacts on energy metabolism or to an anti-inflammatory effect of hypothermia requires further investigation.

Animals↗
PubMed1997

Pitfalls in aneurysm surgery in acute stages.

Since the dawn of aneurysm surgery, many aneurysms present a more complex challenge. Large size, intimacy with critical perforator branches, deep location, atherosclerotic walls, ruptured aneurysms in the elderly and incorporation of afferent or efferent arteries in the dome represent factors that singly or in combination preclude safe clipping while high pressure circulation continues in the aneurysm. Despite the relative frequency of many class of aneurysms, there remains in the neurosurgical community some degree of confusion regarding the detailed anatomic features and the technical aspects of the treatment of these lesions in the acute stage. In our study of 1,433 cases, we have enumerated four aspects of the pitfalls in aneurysm surgery which should be considered when planning the operative approach to these lesions. These four aspects will be reviewed in relation to the aneurysm surgery: (1) inadequate pre-operative planning; (2) inappropriate response to unexpected premature rupture; (3) poor clipping techniques and clip selection; (4) unintentional occlusion or injury of perforating branches. This discussion will simply elaborate our own conceptual and microsurgical technical approach in dissecting the aneurysms. Minimal retraction was used during the whole surgical procedure. The intracranial brain tension was reduced through a ventricular tap for hydrocephalus or evacuation of hematoma prior to aneurysm surgery. A venous pathway was established for blood circulation. Sharp dissection, using our newly designed jet irrigation bipolar suction method was employed. Regarding the clipping of the aneurysm, we used the tentative clipping and the dome coagulation method thereby preventing the ischemic changes and shortening of the entire clipping procedure. Although the strategies, discussed represent simply our approach to this problem, the principles included have proven quite successful and have allowed safe and definitive treatment in the overwhelming majority of patients and also options to overcome the pitfalls in aneurysm surgery.

Acute Disease↗
PubMed1994

Evidence for the colocalization of parvalbumin and glutamate, but not GABA, in the perforant path of the gerbil hippocampal formation: a combined immunocytochemical and microquantitative analysis.

Gerbils (Meriones unguiculatus) are known for their seizure sensitivity, which is dependent on an intact perforant path from the entorhinal cortex to the hippocampus. In contrast with other species, the perforant path in gerbils contains parvalbumin, a cytosolic high-affinity calcium-binding protein. Parvalbumin is known to be present in a subpopulation of GABA-containing neurons and is thought to be responsible for their physiological characteristics of fast spiking activity and lack of spike adaptation. Therefore, the question arose of whether this projection in gerbils is GABAergic or glutamatergic as in other species. In a first approach to this question, the effect of lesioning the origin of the perforant path, the entorhinal cortex, on levels of GABA and glutamate was determined by enzymatic-luminometric assay in single layers of the dentate gyrus of lyophilized brain sections. Parallel sections were cryofixed using an acidified acetone-formaldehyde mixture at -20 degrees C for 48 h, and subsequently stained for parvalbumin immunocytochemistry. Seven days after ablation of the entorhinal cortex, parvalbumin staining was undetectable in the termination zone of the perforant path, the outer two-thirds of the stratum moleculare. In parallel, glutamate content was reduced to 80% of controls (and of the unoperated contralateral side) but unchanged in the inner third of the stratum moleculare and in stratum granulare. GABA content was not significantly altered by the lesion. From these results, we conclude that in the gerbil as in other species, the perforant path contains glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Amygdaloid complex modulates neurotransmission from the entorhinal cortex to the dentate gyrus of the rat.

In urethane-anesthetized rats, single-pulse stimulation of the lateral nucleus of the amygdaloid complex evoked field responses in the dentate gyrus. These responses were similar in many respects to those evoked by stimulation of the monosynaptic perforant path input to the dentate, except for their longer latency. Paired-pulse tests revealed a potent facilitation of perforant path-evoked dentate responses by preceding stimulation of the lateral amygdaloid nucleus. These observations indicate a strong amygdaloid influence on cortico-hippocampal neurotransmission and provide some support for recent anatomical descriptions suggesting that the lateral nucleus of the amygdaloid complex projects to the dentate via a disynaptic pathway relaying in the entorhinal cortex.

Amygdala↗
PubMed1990

Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis.

Kindling of limbic structures induces synaptic reorganization of the mossy fiber pathway in the dentate gyrus. To evaluate the hypothesis that kindling stimulation may also cause neuronal loss in the hilus of the dentate gyrus that could play a role in this synaptic reorganization, neuron counts were obtained using quantitative stereological methods in the hilar polymorphic region of rats kindled by perforant path stimulation. After 3 kindled generalized tonic clonic seizures, there was 12.7% neuronal loss in the hilar polymorphic region compared to controls, but there was no visually apparent lesion. After 30 generalized kindled seizures, the neuronal loss was 40.1%, was visually apparent, and resembled one aspect of the pattern of hilar neuronal loss observed in human hippocampal sclerosis. The results demonstrate that brief sporadic seizures can induce neuronal loss in the hippocampal formation, a brain region implicated in epilepsy, memory, and cognition.

Animals↗
PubMed1993

Transseptal left heart catheterization for radiofrequency ablation of accessory pathways.

In summary, I think it is important to state that transseptal left heart catheterization is a safe procedure when the operator pays meticulous attention to detail. Potential complications can be avoided if the operator: (1) heparinizes the sheath prior to catheterization, (2) fully heparinizes the patient when the catheter and sheath are across the septum, and (3) remembers that the left atrium in these patients is quite small and can be perforated easily by the tapered tip of the transseptal catheter. Transesophageal cardiac ultrasound makes this latter point very clear to anyone doing this procedure.

Arrhythmias, Cardiac↗
PubMed1991

Microsurgery of deep-seated cavernous angiomas: report of 26 cases.

The authors review 26 patients with deep-seated cavernous angiomas which were removed by microsurgery. Ten of the angiomas were located in the insula and basal ganglia, 2 in the thalamus, 5 in the midbrain, 8 in the pons, and 1 in the brachium pontis. The patients were among 73 consecutive cases operated on between August 1983 and December 1989 for symptomatic cavernous angiomas in various locations. In 11 cases total excision of the cavernoma was achieved without producing additional neurological deficits. Postoperative neurological recovery was delayed in 7 patients. In the remaining 8, the complicated postoperative course was caused by bleeding from residual parts of the malformation or damage to long-tract pathways in two cases, respectively, vascular injury during dissection in three cases, and paradoxical air embolism in one case. In order to achieve a satisfactory surgical result, it is stressed that particular attention has to be paid to the operative approach, to careful dissection and complete removal of the malformation, to perforating arteries, and to anomalous venous drainage.

Adolescent↗
PubMed2003

Influence of the whole-cell patch-clamp configuration on electrophysiological properties of the voltage-dependent sodium current expressed in MDA-MB-231 breast cancer cells.

Voltage-gated ionic channels are known to be involved in oncogenesis. However, only a few studies describe the functional characteristics of these channels or the mechanisms by which they are involved in the proliferation and invasive processes. Breast cancer cells proliferate and migrate under the constant activation of growth factors, hormones, extracellular matrix interactions, etc. It would thus not be surprising if the activity of the ionic channels was modulated by intracellular regulation pathways such as kinases or phosphatases, which in turn can affect oncogenic properties. In the present study, we investigated some of the electrophysiological properties of the fast inward sodium current found in the breast cancer cell line MDA-MB-231 with two configurations of the patch-clamp technique. With perforated patch, a configuration which allows to keep the cytoplam intact, the mean current amplitude was lower, the relative conductance-voltage relationship was shifted to more positive potentials and the recovery from inactivation was accelerated when compared to ruptured patch, where the cytoplasm is dialysed by the intrapipette solution. There was no difference in availability-voltage (pseudo-steady-state inactivation) relationship and in time to peak of the current. These results suggest that regulation mechanisms, possibly involving kinases or phosphatases, are switched off when the cytoplasm is diluted. We propose that such a regulation can modulate the functioning of the channels even in the absence of membrane voltage changes, which in turn can affect oncogenic properties. This finding is of importance when evaluating the physiopathological role of ionic channel in cancer development.

Animals↗
PubMed1999

Inhibitory and excitatory responses of olfactory receptor neurons of xenopus laevis tadpoles to stimulation with amino acids

Recordings were made from olfactory receptor neurons of Xenopus laevis tadpoles using the patch-clamp technique to investigate the responses of these cells to odorants. Four amino acids (glutamate, methionine, arginine and alanine) both individually and as a mixture were used as stimuli. Of the 156 olfactory neurons tested, 43 showed a response to at least one of the stimuli. Of the cells tested, 19 % responded to glutamate, 16 % to methionine, 12 % to arginine and 10 % to alanine. Each amino acid was able to induce both excitatory and inhibitory responses, although these occurred in different cells. Each amino acid produced approximately equal numbers of inhibitory and excitatory responses. Inhibitory responses could best be observed in the perforated-patch configuration using gramicidin as an ionophore and a recording configuration that is a current-clamp for fast signals and a voltage-clamp for slow signals. The diversity of the odorant responses, in particular the existence of excitatory and inhibitory responses, is not consistent with a single transduction pathway in olfactory neurons of Xenopus laevis tadpoles.

Journal Article↗
PubMed1993

Induction of noncatalytic TrkB neurotrophin receptors during axonal sprouting in the adult hippocampus.

Brain-derived neurotrophic factor (BDNF) and its signal transducing receptor, the TrkB tyrosine protein kinase, are expressed at high levels in the hippocampus of the adult brain, suggesting a role for BDNF mechanisms in neuronal plasticity. To test this hypothesis, we used defined lesions of perforant path and fimbria-fornix, two major hippocampal afferents, to remove synapses on dendrites of dentate gyrus granule cells and pyramidal cells of Ammon's horn and induce synaptic rearrangements. These combined lesions remove afferent connections from entorhinal cortex and septum and produce massive sprouting of axons of the commissural/associational pathways into the molecular layer of the hippocampal dentate gyrus. At days 1, 3, and 6, the lesions decreased BDNF mRNA expression ipsilaterally to approximately 50% of control, with complete recovery at 14 d. The lesions did not alter trkB mRNA levels in neuronal layers of the hippocampus; however, they resulted in a pronounced induction of trkB mRNA expression in hippocampal non-neuronal cells 6-14 d after lesioning. The induction corresponded in time and place to the synaptic reorganization in the lesioned hippocampus. The mRNA species newly induced by the lesions corresponded to those transcripts encoding the noncatalytic TrkB receptor isoform that lacks the cytoplasmic protein kinase domain. Expression of mRNAs coding for neurotrophin-3 and the TrkC tyrosine protein kinase were not altered by the lesions. The findings suggest that truncated noncatalytic TrkB molecules expressed on the surface of glial cells play an important role in plasticity of the adult brain, possibly regulating the concentration of bioactive neurotrophins or the responsiveness of neurotrophin receptors. Alternatively, they may play a role in presenting neurotrophin molecules to growing axons.

Animals↗
PubMed2005

Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways.

Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca(2+) concentration ([Ca(2+)]i), which is determined by Ca(2+) influx and release from intracellular Ca(2+) storage sites. Ca(2+) influx is via voltage-gated Ca(2+) channels, which are activated by cell depolarization. Membrane potential is mainly determined by transmembrane K(+) channels. The present study investigates the in vitroeffect of ghrelin on membrane voltage-gated K(+) channels in the GH3 rat somatotrope cell line. Nystatin-perforated patch clamp recording was used to record K(+) currents under voltage-clamp conditions. In the presence of Co(2+) (1 mM, Ca(2+) channel blocker) and tetrodotoxin (1 microM, Na(+) channel blocker) in the bath solution, two types of voltage-gated K(+) currents were characterized on the basis of their biophysical kinetics and pharmacological properties. We observed that transient K(+) current (IA) represented a significant proportion of total K(+) currents in some cells, whereas delayed rectifier K(+) current (IK) existed in all cells. The application of ghrelin (10 nM) reversibly and significantly decreased the amplitude of both IA and IK currents to 48% and 64% of control, respectively. Application of apamin (1 microM, SK channel blocker) or charybdotoxin (1 microM, BK channel blocker) did not alter the K(+) current or the response to ghrelin. The ghrelin-induced reduction in K(+) currents was not affected by PKC and PKA inhibitors. KT5823, a specific PKG inhibitor, totally abolished the K+ current response to ghrelin. These results suggest that ghrelin-induced reduction of voltage-gated K(+) currents in GH3 cells is mediated through a PKG-dependent pathway. A decrease in voltage-gated K(+) currents may increase the frequency, duration, and amplitude of action potentials and contribute to GH secretion from somatotropes.

Animals↗
PubMed1995

Regulation of cyclic nucleotide-gated channels and membrane excitability in olfactory receptor cells by carbon monoxide.

1. The effect of the putative neural messenger carbon monoxide (CO) and the role of the cGMP second-messenger system for olfactory signal generation was examined in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With the use of whole cell voltage-clamp recordings in combination with a series of ionic and pharmological tests, it is demonstrated that exogenously applied CO is a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels previously described to mediate odor transduction. 3. Several lines of evidence suggest that CO mediates its effect through stimulation of a soluble guanylyl cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion is based on the findings that CO responses show an absolute requirement for guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect of CO on CNG currents in the absence of GTP is detectable, and that a blocker of sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation. This analysis implies that CO is a potent activator of olfactory sGC. 5. Perforated patch recordings using amphotericin B demonstrate that low micromolar doses of CO effectively depolarize the membrane potential of ORNs through tonic activation of CNG channels. This effect in turn regulates excitable and adaptive properties of ORNs and modulates neuronal responsiveness. 6. These data argue for an important role of the cGMP pathway in olfactory signaling and support the idea that CO may function as a diffusible messenger in the olfactory system.

Adaptation, Physiological↗
PubMed1986

[Anatomico-functional approach to the mechanisms of memory: analysis by deoxyglucose of the limbic activation induced by electric stimulation of the mouse entorhinal cortex].

Previous behavioral studies using post-training electrical stimulation of the brain have suggested that the lateral entorhinal cortex (LEC) is involved in mnemonic processes. In an attempt to characterize in vivo the neural pathways activated by LEC stimulation, regional patterns of uptake of 14C-2-deoxy-D-glucose (2-DG) were assessed in BALB/c mouse brain. The animals were implanted with a bipolar electrode in the LEC and a catheter in the jugular vein. In addition, four animals received an electrolytic lesion of the perforant path (PP) in order to disconnect the LEC from the hippocampus. The LEC was stimulated at subconvulsive intensity for 5 min. before and 30 min. after an injection of 2-DG. Stimulation of the LEC produced significant increases in 2-DG radioactivity in the hippocampus (dentate gyrus, CA3, CA1), subiculum and pre-subiculum. Demonstrable labelling was found in brain areas, beyond the hippocampal formation: piriform cortex, amygdala, cingulate cortex, Diagonal Band of Broca, the medial and lateral septal nuclei and the medial forebrain bundle. After PP lesion, the metabolic activity disappeared ipsilaterally in subiculum, dorsal part of the hippocampus, in some thalamic nuclei and in mammillary bodies, but all other extra-hippocampal labelling was unchanged. These data considered along with our previous behavioral results, suggest that LEC stimulation may act on mnemonic processes by the recruitment of cortical and subcortical extra-hippocampal structures (e.g. amygdala and cingulate cortex) directly or indirectly connected to the entorhinal cortex.

Animals↗