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PubMed1993

Haloperidol-induced blockade of induction of long-term potentiation in perforant path-dentate gyrus pathway in chronically prepared rabbits.

We investigated the effects of the representative neuroleptic and dopamine receptor antagonist haloperidol (HPD) on the induction of long-term potentiation (LTP) or on the previously induced LTP in the perforant path-dentate gyrus pathway in chronically prepared rabbits. The IP HPD injection of 0.8 mg/kg blocked the induction of LTP when it was given before LTP-inducing tetanic stimulations, although this dose showed virtually no effect on the baseline control responses in the perforant path-dentate gyrus pathway to single shocks. However, neither 0.8-mg/kg nor 1.6-mg/kg HPD doses affected the previously induced LTP. The possible mechanisms underlying these results, notably the HPD-induced blockade of LTP induction, are discussed, especially in association with the inhibitory action of HPD on calmodulin-mediated events rather than dopaminergic function.

Animals↗
PubMed2006

Coming full circle: an evidence-based definition of the timing and type of surgical management of very low-birth-weight (<1000 g) infants with signs of acute intestinal perforation.

OBJECTIVE: Gut disruption in very low birth weight follows 1 of 3 clinical pathways: isolated perforation with sudden free air, metabolic derangement (MD) complicated by appearance of free air, or progressive metabolic deterioration without evidence of free air. To refine evidence-based indications for peritoneal drainage (PD) vs laparotomy (LAP), we hypothesized that MD acuity is the determinant of outcome and should dictate choice of PD or LAP. METHODS: Very low-birth-weight infants referred for surgical care because of free intraperitoneal air or MD associated with signs of enteritis were evaluated by univariate or multivariate logistic regression to investigate the effect on mortality of MD and initial surgical care (LAP vs PD). Metabolic derangement was scaled by assigning 1 point each for thrombocytopenia, metabolic acidosis, neutropenia, left shift of segmented neutrophils, hyponatremia, bacteremia, or hypotension. Laparotomy and PD were stratified by MD acuity, and odds of mortality were calculated for each surgical option. RESULTS: From October 1991 to December 2003, 65 very low-birth-weight infants with suspected gut disruption were referred for surgical care. Peritoneal drainage and LAP infants had similar birth weight and gastrointestinal age, neither of which predicted mortality. Despite a higher incidence of isolated perforation with sudden free air in PD infants, the incidence of MD and overall mortality were similar for PD and LAP. Multivariate logistic regression demonstrated MD to be the best predictor of mortality (odds ratio [OR], 4.76; confidence interval [CI], 1.41-16.13, P = .012), which significantly increased with interval between diagnosis to surgical intervention (P < .05). Infants with MD receiving PD had a 4-fold increase in mortality (OR, 4.43; CI, 1.37-14.29; P = .0126). Conversely, those without MD and sudden free air who underwent LAP had a 3-fold increase in mortality (OR, 2.915; CI, 1.107-7.692; P = .03.) Of 5, 3 failed PD were "rescued" by LAP. CONCLUSIONS: The dramatic difference in mortality odds based on surgical option in the presence of MD defines the critical importance of a thorough assessment of physiological status to exclude MD. Absence of MD warrants consideration for PD, especially for sudden intraperitoneal free air. Overwhelming MD may limit options to PD; however, salvage of 3 of 5 infants with failed PD demonstrates the value of LAP, whenever possible, for infants with MD.

Acute Disease↗
PubMed2000

Deficits in nitric oxide production after tetanic stimulation are related to the reduction of long-term potentiation in Schaffer-CA1 synapses in aged Fischer 344 rats.

In the present study, we investigated whether nitric oxide (NO) production after tetanic stimulation is involved in long-term potentiation (LTP) in Schaffer-CA1 synapses in both young adult and aged rats. The changes in both the population spike amplitude and NO metabolites, nitrite (NO2-) and nitrate (NO3-), in the CA1 region were simultaneously determined before and after tetanic stimulation. Increases in NOx (NO2- plus NO3-) levels in the CA1 region were observed after tetanic stimulation in young adult rats as well as increase in the population spike amplitude. In aged rats, LTP was significantly inhibited compared with that in young adult rats. No increase in NOx level after tetanic stimulation was observed in aged rats. These findings directly demonstrated that NO production might be involved in the process of LTP formation in Schaffer-CA1 synapses of the rat hippocampus, and that the deficiency of hippocampal NO production might be responsible for reduction of LTP formation in aged rats.

Action Potentials↗
PubMed1998

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro.

1. Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. 2. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n = 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n = 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n = 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n = 2) characterized by their dense, compact axonal and dendritic arbour. 3. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynatpic pyramidal cells. 4. Anatomically recovered R-LM interneurons (n = 22) had a mean resting membrane potential of -56.7 +/- 3.6 mV, a membrane time constant of 12.9 +/- 7.7 ms and an input resistance of 86.4 +/- 29.2 M omega. Depolarizing current pulses generally elicited overshooting action potentials (70.8 +/- 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 +/- 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. 5. Basket cells, Schaffer-associated and neurogliaform interneurons elicited small-amplitude (< 2 mV), short-latency IPSPs in postsynaptic pyramids (n = 5, 13 and 1, respectively). Those interactions in which an effect was elicited with the repetitive activation of the presynaptic neuron (n = 13) showed a substantial degree of postsynaptic response summation. Unitary IPSPs had fast kinetics and, whenever tested (n = 5; 1 basket cell and 4 Schaffer-associated interneurons), were abolished by the GABAA receptor antagonist bicuculline. 6. Thus, R-LM interneurons comprise several distinct populations which evoke fast GABAA receptor mediated IPSPs. The domain-specific innervation of postsynaptic pyramidal cells suggests functionally diverse effects on the integration of afferent information in functionally non-equivalent compartments of pyramidal cells.

Action Potentials↗
PubMed1994

Carbamazepine-induced blockade of induction of long-term potentiation in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

We investigated the effects of a representative anti-epileptic or anti-psychotic drug, carbamazepine (CBZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Pharmacokinetically injected low-dose CBZ, which produced steady serum levels of 2.2-3.3 micrograms/ml (mean +/- S.D. 2.85 +/- 0.40), variably affected the induction of LTP, blocking it or showing almost no effect. The high-dose CBZ, which produced steady serum levels of 6.5-8.6 micrograms/ml (8.01 +/- 0.87), always blocked the induction of LTP. These results indicate that CBZ dose-dependently blocks the induction of LTP. The possible mechanisms underlying this blockade are discussed, especially in association with the possible inhibitory action of CBZ on N-methyl-D-aspartate (NMDA) receptors.

Animals↗
PubMed1999

[125 reinterventions for recurrent popliteal varicose veins after excision of the short saphenous vein. Anatomical and physiological hypotheses of the mechanism of recurrence].

Recurrence of popliteal varicose veins has long been attributed to insufficient excision of an incompetent short saphenous vein. Indeed, recurrence is still frequent after surgery of the short saphenous. In order to assess the risk of insufficient excision and study the mechanism of recurrence, we reviewed 125 popliteal procedures for recurrence after excision of an incompetent short saphenous vein. Among this series, 48 were personal procedures and among these, 43 had been performed without preoperative ultrasound explorations prior to 1991. Recurrences were classified into five categories (table I) according to the anatomic presentation at reoperation. Type 1) 17 patients had an intact short saphenous (13.6%) with either an inadequate incision or a simple recanalized suture. Type 2) 53 patients had a long stump (42.4%) with new superficial varicose communications. Type 3) 4 patients had a small residual and incompetent short saphenous trunk (3.2%), 20 patients had both a long stump and an incompetent residual trunk (16%). Type 4) 29 patients had incompetent popliteal perforating veins (23.2%). Type 5) 2 patients developed recurrence on a new varicose communication which followed the posterior nerves of the thigh. Among our personal series, 43 reoperations for recurrence were performed without preoperative duplex Doppler exploration. Among them, excision was insufficient in 38 (table II). The 5 patients reoperated after preoperative ultrasound exploration had a popliteal perforating vein. Recurrence with a popliteal perforator was significantly more frequent in men than in women (table III). The delay to reoperation for popliteal recurrence after surgery of the short saphenous (50% at 6 years) was significantly shorter than the delay to reoperation for inguinal recurrence after surgery of the greater saphenous (50% at 12 years) (table V). Insufficient excision was observed in 75.2% of the cases, but 23.2% of the recurrences were due to the development of an incompetent popliteal perforating veins. These perforating veins were residual stumps of the short saphenous with complex pathways, unrecognized perforating veins associated with the short saphenous at the first operation, or a new popliteal incompetence. Ces perforantes de la fosse poplitée pourraient être des moignons résiduels de petites saphènes à trajet complexe, des perforantes méconnues associées à la petite saphène developing in several perforating vessels described in the popliteal fossa. The lack of preoperative ultrasound data made it difficult to interpret these recurrences. The development of perforating veins in the popliteal fossa is a type of recurrence which is probably the expression of particular hemodynamic phenomena in the popliteal venous circulation. These phenomena probably involve the flexion of the popliteal vein, the contraction of the calf muscles, and also popliteal valvular incompetence frequently demonstrated in patients who develop short saphenous vein insufficiency.

Female↗
PubMed1996

Clozapine-induced potentiation of synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

To examine the contribution of N-methyl-D-aspartate (NMDA) receptors in the mechanisms underlying the action of antipsychotics, we investigated the effects of a representative atypical antipsychotic, clozapine (CLZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Eventually, neither low (10 mg/kg) nor high (20 mg/kg) doses of CLZ intraperitoneally injected had any effects on LTP induction. However, the high dose CLZ always potentiated the ordinary synaptic responses induced by single stimulations before the LTP induction. The present study indicates a new finding, the presence of "CLZ-induced potentiation', although it needs further investigation whether NMDA receptors contribute to this potentiation.

Animals↗
PubMed2006

Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus.

The dentate gyrus (DG) is among the few areas in the mammalian brain where production of new neurons continues in the adulthood. Although its functional significance is not completely understood, several lines of evidence suggest the role of DG neurogenesis in learning and memory. Considering that long-term potentiation (LTP) is a prime candidate for the process underlying hippocampal learning and memory, these results raise the possibility that LTP and neurogenesis are closely related. Here, we investigated whether or not LTP induction in the afferent pathway triggers enhanced proliferation of progenitor cells in the DG. LTP was induced by tetanic stimulation in perforant path-DG synapses in one hemisphere, and the number of newly generated progenitor (BrdU-labeled) cells in the DG was quantified. Compared with the control hemisphere (stimulated with low-frequency pulses), the LTP-induced hemisphere contained a significantly higher number of newly generated progenitor cells in the dorsal as well as ventral DG. When CPP, an NMDA receptor antagonist, was administered, tetanic stimulation neither induced LTP nor enhanced progenitor cell proliferation, indicating that NMDA receptor activation, rather than tetanic stimulation per se, is responsible for enhanced progenitor proliferation in the control animal. Our results show that tetanic stimulation of perforant path sufficient to induce LTP increases progenitor proliferation in adult DG in an NMDA receptor-dependent manner.

Adult Stem Cells↗
PubMed2002

Associative long-term potentiation (LTP) among extrinsic afferents of the hippocampal CA3 region in vivo.

Monosynaptic perforant path projections to the CA3 region of the hippocampus are anatomically and physiologically substantial pathways that relay cortical input directly to the hippocampus proper. Despite the suggested relevance of these direct pathways in models of information processing within the CA3 region, surprisingly few studies have characterized synaptic plasticity in these direct cortical projections to the CA3 region. We assessed the ability of perforant path projections, and commissural/associational projections to the hippocampal CA3 region to both induce or display associative LTP in vivo. In pentobarbital-anesthetized adult rats, trains delivered to either the medial or lateral perforant pathway at current intensities normally insufficient to induce LTP displayed associative LTP when these same trains were delivered in conjunction with high-intensity trains to the alternate perforant pathway. Similarly, associative LTP is induced at intrinsic commissural/associational-CA3 (C/A-CA3) synapses when weak C/A trains were delivered in conjunction with high-intensity trains to either the medial or lateral perforant pathway. Associative LTP also was observed at medial and lateral perforant path-CA3 synapses when weak perforant path trains were tetanized in conjunction with high-intensity trains delivered to C/A-CA3 synapses. Thus direct perforant path-CA3 synapses and commissural/associational-CA3 synapses can modify and be modified by other CA3 afferents in an associative manner, verifying a requirement for synaptic plasticity explicit in models of autoassociative information processing in the CA3 region.

Afferent Pathways↗
PubMed2006

The survival rate and prognostic factors in 26 perforated colorectal cancer patients.

PURPOSE: The treatment for perforated colorectal cancer is not easy and the prognosis for this disease is not so predictable. There are some controversies about performing radical operations because colorectal cancer perforation was considered as an advanced stage disease due to the possibility of tumor cell dissemination through the perforation site. METHODS: We selected and enrolled 26 patients with perforated colorectal cancers among the 1,227 patients who underwent operation for colorectal cancer. These cases were retrospectively analyzed by using their medical records and clinicopathological data. RESULTS: Twenty-eight cases (2.3%) with perforated colorectal cancers were studied and the overall operative mortality rate was 11%. The overall 5-year survival rate was 57.8% when excluding the operative mortality. The overall 5-year cancer-free survival rate was 52.8%. There were significant differences in the survival rate and the cancer-free survival rate between the stages (p=0.008 and p<0.001, respectively). A univariate analysis of the prognostic factors revealed that the number of the metastatic lymph nodes (p=0.018) and the perforation proximal to the cancer (p=0.005) were significantly correlated to worse survival, and the higher number of the metastatic lymph nodes was correlated to a poorer cancer-free survival rate (p<0.001). CONCLUSION: For the perforated colorectal cancers, the stage, the perforation proximal to the cancer, and the number of the metastatic lymph nodes were correlated, with the survival and the cancer-free survival as factors of a poor prognosis. The surgical approach selected for perforated colorectal cancer should be in line with the principles of an appropriate cancer operation because the clinical pathway of perforated colorectal cancer is similar to that of uncomplicated colorectal cancer.

Adult↗
PubMed2005

Functional properties of ES cell-derived neurons engrafted into the hippocampus of adult normal and chronically epileptic rats.

PURPOSE: Embryonic stem (ES) cell-based therapy strategies are thought to bear considerable promise in chronic neurologic disorders. Nonetheless, studies addressing the functional properties of ES cell-derived progeny after transplantation into the adult, pathologically modified CNS are scarce. METHODS: We therefore transplanted ES cell-derived neural precursors expressing enhanced green fluorescent protein only in neuronal progeny bilaterally into the hippocampi of pilocarpine-treated chronically epileptic and sham-control rats. Whole-cell patch-clamp recordings of identified ES cell-derived neurons (ESNs) in hippocampal slices were performed 13 to 34 days after transplantation. RESULTS: Most ESNs were found in clusters at the transplant site and did not migrate into host tissue. However, they gave rise to a dense network of processes extending over large distances into the host tissue. All ESNs possessed the ability to generate action potentials and expressed voltage-gated Na+ and K+ currents, as well as hyperpolarization-activated currents. Likewise, most ESNs received non-N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)A receptor-mediated synaptic input. Both types of synapses displayed intact short-term plasticity. An unusual feature of the majority of ESNs was the occurrence of spontaneous pacemaking activity at frequencies approximately 3 Hertz. No obvious differences were found between the functional properties of ESNs in sham-control and in pilocarpine-treated rats. CONCLUSIONS: After transplantation into adult control and epileptic rats, ESNs displayed intrinsic and synaptic properties characteristic of neurons. Even though ESNs remained close to the transplant site, the formation of extensive networks of graft-derived processes may be useful for ES cell-based substance delivery.

Afferent Pathways↗
PubMed2001

Lesions of the entorhinal cortex impair acquisition of hippocampal-dependent trace conditioning.

Rabbits with the electrolytic lesions of bilateral entorhinal cortex (EC) were trained with the hippocampal-dependent trace conditioning of the nictitating membrane response. The multiple-unit activity of the hippocampal CA1 region was recorded during conditioning. The conditioned stimulus was a tone (1 kHz, 85 dB, 200-ms duration), the unconditioned stimulus was a corneal air puff (3 psi, 150-ms duration), and the interstimulus interval was 750 ms. The EC-lesioned animals showed only 30% conditioned response (CR) by the ninth session while the sham-operated animals showed above 80% CR. The lesioned animals did not show learning-related changes in the hippocampal activity. When the training was switched to the 300-ms interstimulus interval trace conditioning, both groups learned above 80% CR. The EC-lesioned animals, however, showed less learning-related activity in the hippocampus than the sham-operated animals. These results suggest that the development of the learning-related activity in the hippocampus depends on the intact EC, and that the EC may provide a possible pathway conveying learning information from the cerebellum or cerebral cortex to the hippocampus during the trace conditioning.

Animals↗
PubMed2002

Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry.

There is increasing evidence that the fasciculus retroflexus (FR) represents a 'weak link' following the continuous administration of drugs of abuse. A variety of drugs which predominantly potentiate dopamine, including D-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from lateral habenula, through the sheath of FR, to midbrain cells such as SN, VTA, and raphe. For some drugs, such as cocaine, this is virtually the only degeneration induced in brain. Continuous nicotine also selectively induces degeneration in FR, but in the other half of the tract, i.e. in axons from medial habenula through the core of the tract to interpeduncular nucleus. This phylogenetically primitive tract carries much of the negative feedback from forebrain back onto midbrain reward cells, and the finding that these descending control pathways are compromised following simulated drug binges has implications for theories of drug addiction but also psychosis in general.

Amphetamine↗
PubMed2005

Sigmoid perforation by compressed carbon dioxide.

Self-induced injuries of the bowel have various accidental mechanisms. This is a report of a 35-year-old patient with disruption of the recto-sigmoid junction caused by carbon dioxide (CO2) originating from a bottle of sparkling wine, which was introduced transanally for sexual stimulation. The patient underwent resection of the recto-sigmoid junction and primary anastomosis. The postoperative course was uneventful except for wound infection. The patient was discharged 12 days later. The physical backgrounds, the pathological pathways for perforation and diagnostic modalities including diagnostic pitfalls are critically discussed.

Accidents, Home↗
PubMed1998

Superior caval venous syndrome after atrial switch procedure: relief of complete venous obstruction by gradual angioplasty and placement of stents.

Superior caval venous syndrome is one of the late problems known to occur after Mustard repair of complete transposition. Reoperation may leave residual stenosis, and carries substantial risk for the patient. It is now feasible to use intravascular stents to overcome systemic venous baffle obstructions, and such an approach is probably more effective. The purpose of our study therefore, was to assess immediate and medium term results of inserting stents subsequent to gradual balloon enlargement of acquired atresia of the intraatrial baffle in patients who had undergone an atrial switch operation. We investigated five patients with complete obstruction of the superior caval venous pathway at perforation of the atretic segment was achieved using a guide wire technique. The procedure was successful in all patients. Gradual angioplasty was performed and intravascular stents were implanted. The pressure in the superior caval vein dropped to normal values, symptoms improved, and the patency of the newly created venoatrial communication was proven at mid-term follow-up. Thus critical obstructions at the superior caval venous pathway after the Mustard procedure can be reopened by interventional catheterization. Implantation of balloon-expandable intravascular stents is safe and effective in the acute relief of the obstructions, but careful long-term follow-up is mandatory.

Adolescent↗
PubMed2003

Stimulation-induced reset of hippocampal theta in the freely performing rat.

Previous research has suggested that visual and auditory stimuli in a working memory task have the ability to reset hippocampal theta, perhaps allowing an organism to encode the incoming information optimally. The present study examined two possible neural pathways involved in theta resetting. Rats were trained on a visual discrimination task in an operant chamber. At the beginning of a trial, a light appeared over a centrally located lever that the rat was required to press to receive a water reward. There was a 30-s intertrial interval before the next light stimulus appeared. After learning the task, all rats received surgical implantation of stimulating electrodes in both the fornix and the perforant path and recording electrodes, bilaterally in the hippocampus. After surgery, theta was recorded before and after the light stimulus to determine whether resetting to the visual stimulus occurred. During the intertrial interval, rats received single-pulse electrical stimulation of either the fornix or perforant path. Theta was recorded both before and after the electrical stimulation to determine whether resetting occurred. In this experiment, hippocampal theta was reset after all three stimulus conditions (light, perforant path, and fornix stimulation), with the greatest degree of reset occurring after the fornix stimulation. The results suggest that activation of the perforant path and fornix may underlie theta reset and provide a mechanism by which the hippocampus may enhance cognitive processing.

Animals↗
PubMed2006

Pathway specificity of dendritic spine morphology in identified synapses onto rat hippocampal CA1 neurons in organotypic slices.

The output of the hippocampus is largely determined by interaction of the three excitatory pathways that impinge on CA1 pyramidal neurons. These synapses, formed by axons of: (1) CA3 pyramidal neurons; (2) neurons of the entorhinal cortex (EC); and (3) neighboring CA1 neurons, are all potentially plastic. Here, we take advantage of the accessibility of the organotypic slice preparation to identify the type of spines with which each of these pathways forms synapses, at different developmental stages. Recent reports have shown that morphology of dendritic spines is activity-dependent with large mushroom spines being thought to represent stronger synaptic connections than thin or stubby spines. Although in a wide range of preparations, mushroom spines represent only 15% of spines across the whole dendritic tree, we find that this proportion is highly pathway specific. Thus in organotypic slices, the axons of CA3 neurons form synapses with mushroom spines on CA1 neurons in approximately 50% of cases, whereas this spine type is rare (<10%) in either of the other two pathways. This high proportion of mushroom spines only occurs after spontaneous excitatory activity in the CA1 cells increases over the second week in vitro. Previous studies suggest that pathway specificity also occurs in vivo. In tissue fixed in vivo, it is the synapses of distal apical dendrites thought to be formed by axons originating in the EC that are richer in mushroom spines. Hence, contrary to previous suggestions, the proportion of mushroom spines is clearly not an intrinsic property of the pathway but rather a characteristic dependent on the environment. We suggest that this is most likely a result of the previous activity of the synapses. The fact that, despite the large differences in pathway specificity between preparations, the overall proportion of different spine types remains unchanged, suggests a strong influence of homeostasis across the network.

Animals↗