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M J Sanders

Publications and source records attributed to M J Sanders.

At least 19 recordsLinked to original sources
PubMed2001

Behavioral, electrophysiological, and histopathological consequences of mild fluid-percussion injury in the rat.

Metabolic dysfunction in the relay nuclei of the rat vibrissa circuit follows traumatic brain injury (TBI). This study examined the effects of mild (1.4-1.5 atm) parasagittal fluid-percussion injury on the electrophysiology of this circuit. TBI caused significant reductions in slope and increases in latency of vibrissa-evoked field potentials 3 days after injury. Assessment of open-field swimming revealed an increase in thigmotaxis 2 days after injury. TBI caused mild selective cortical damage and limited axonal swelling at the injury site. Thus mild injury disrupts somatosensory electrophysiology and exploratory behavior.

Afferent Pathways↗
PubMed2001

Sex differences, context preexposure, and the immediate shock deficit in Pavlovian context conditioning with mice.

The acquisition of context fear in rats is affected by variables such as the sex of the animal, the placement to shock interval (PSI), and preexposure to the context. The current experiments assessed the effects of these variables on context conditioning in mice (C57BL/6). In Experiment 1, mice were placed in a chamber and received a single shock 5s, 20 s, 40s, 60s, 180s, or 720s later. Increasing the PSI produced corresponding increases in conditional freezing during the context test. In addition, male mice acquired more context conditioning than female mice did but only at intermediate PSIs. In Experiment 2, preexposure to the context before training alleviated the sex difference found with an intermediate PSI. The results are discussed in terms of configural learning theory and are argued to be contrary to the predictions of scalar expectancy theory.

Animals↗
PubMed2000

Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat.

Traumatic brain injury (TBI) can produce chronic cognitive learning/memory deficits that are thought to be mediated, in part, by impaired hippocampal function. Experimentally induced TBI is associated with deficits in hippocampal synaptic plasticity (long-term potentiation, or LTP) at acute post-injury intervals but plasticity has not been examined at long-term survival periods. The present study was conducted to assess the temporal profile of LTP after injury and to evaluate the effects of injury severity on plasticity. Separate groups of rats were subjected to mild (1.1-1.4 atm), moderate (1.8-2.1 atm), or severe (2.2-2.7 atm) fluid percussion (FP) injury (or sham surgery) and processed for hippocampal electrophysiology in the first or eighth week after injury. LTP was defined as a lasting increase in field excitatory post-synaptic potential (fEPSP) slope in area CA1 following tetanic stimulation of the Schaffer collaterals. The fEPSP slope was measured for 60 min after tetanus. Assessment of LTP at the acute interval (6 days) revealed modest peak slope potentiation values (129-139%), which declined in each group (including sham) over the hour-long recording session and did not differ between groups. Eight weeks following injury, slices from all groups exhibited robust maximal potentiation (134-147%). Levels of potentiation among groups were similar at the 5-min test interval but differed significantly at the 30- and 60-min test intervals. Whereas sham slices showed stable potentiation for the entire 60-min assessment period, slices in all of the injury groups exhibited a significant decline in potentiation over this period. These experiments reveal a previously unknown effect of TBI whereby experimentally induced injury results in a chronic inability of the CA1 hippocampus to maintain synaptic plasticity. They also provide evidence that sham surgical procedures can significantly influence hippocampal physiology at the acute post-TBI intervals. The results have implications for the mechanisms underlying the impaired synaptic plasticity following TBI.

Animals↗
PubMed2000

Paramedic prep.

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Curriculum↗
PubMed1999

Cognitive function following traumatic brain injury: effects of injury severity and recovery period in a parasagittal fluid-percussive injury model.

Previous work in this laboratory has demonstrated that rats show substantial deficits on the cued and hidden versions of the Morris water maze, as well as an apparent time-dependent recovery over a period of months, following moderate parasagittal fluid-percussion (FP) injury. However, the longitudinal nature of those studies precluded definitive statements regarding recovery because of the possible confound of practice-dependent improvements in performance. The present experiments were undertaken to address this issue and to investigate more closely the relationship between impact severity and posttraumatic learning/memory deficits, which have not been examined thoroughly in this model. Separate groups of rats were subjected to mild (1.1 to 1.4 atm), moderate (1.8 to 2.1 atm), or severe (2.2 to 2.7 atm) FP injury (or sham surgery) and tested on several water maze tasks at either 5 days or 8 weeks after injury. Moderately and severely injured animals showed impairment in acquisition of the hidden platform task at both time points. Cued platform task performance was impaired significantly in severely injured animals 8 weeks after insult. Mildly injured animals exhibited no significant deficits on either task at either time point. The results indicate that deficits on the hidden platform task are more robust than those on the cued platform task, and that performance on both tasks is dependent on injury severity. They also indicate that the learning/memory deficits in this model are relatively enduring, suggesting that the model is a reasonable one for assessing potential treatment regimens.

Animals↗
PubMed1998

The freshwater river crab, Potamonautes warreni, as a bioaccumulative indicator of iron and manganese pollution in two aquatic systems.

The aim of this study was to determine the potential use of the freshwater river crab, Potamonautes warreni, as a bioaccumulative indicator of iron and manganese pollution in aquatic ecosystems. Water and sediment analysis of the two study sites (Germiston Lake and Potchefstroom Dam) revealed that while levels of manganese were higher in Germiston Lake, iron concentrations were higher in Potchefstroom Dam. Metal analysis of P. warreni revealed that while the crabs from Potchefstroom Dam contained slightly higher iron levels than those from Germiston Lake, manganese concentrations in P. warreni from the latter site were significantly higher than those in the crabs from the former site. Iron and manganese levels in these organisms were influenced by the size, mass, and sex of the crabs on occasion, but these relationships were not always consistent at both of the sites. The results of this study clearly indicate that the ultimate levels of iron and manganese attained in P. warreni do vary depending on the site from which animals are collected. From this, it is suggested that these crustaceans be incorporated into biomonitoring protocols, particularly in areas that are subjected to elevated metal levels in the environment

Animals↗
PubMed1997

Physiological evidence for hippocampal disinhibition resulting from activation of the median raphe.

The mechanism underlying median raphe (MR)-induced facilitation of hippocampal synaptic transmission was investigated by recording stimulus-evoked field potentials and unitary responses in urethane-anesthetized rats. Stimulation of the MR 40 ms prior to perforant path (PP) activation significantly increased the magnitude of PP-evoked granule cell population spikes (median increase = 78%) without affecting population EPSP slope. Injection of homocysteic acid into the vicinity of the MR also facilitated PP-evoked granule cell population spikes, in a dose-dependent manner. Nineteen dentate hilar units were characterized as putative interneurons on the basis of their waveform characteristics and their response to PP stimulation. Electrical activation of the MR inhibited spontaneous or PP-evoked activity in the majority (75%) of these cells; the remaining cells were unaffected. MR stimulation also inhibited spontaneous activity in a large proportion (60%) of putative interneurons in CA1. The present results provide evidence that neurons within the raphe modulate hippocampal throughput by altering discharge of non-principal cells. These data, thus, support the idea that disinhibition is a common mechanism by which extrahippocampal structures modulate information flow through the hippocampus.

Animals↗
PubMed1996

Model development and analysis of tenidap-induced proteinuria in the rat.

Tenidap is a novel antirheumatic agent that causes a mild, reversible proteinuria in human clinical trials. In order to achieve a mechanistic understanding and safety perspective of the proteinuric effects of tenidap observed in clinical trials, female Sprague-Dawley rats were treated with up to 100 mg/kg/day of tenidap in the diet for 4 to 6 weeks followed by a 1- to 6-week reversal period. Pharmacokinetics and measurements of renal function and histology were assessed during the study. Sustained high plasma concentrations of tenidap [area under the plasma concentration curve (0-24 hr) of 941-1021 micrograms. hr/ml and peak plasma concentration of 61-67 micrograms/ml] increased urinary protein, albumin and phosphate excretion (2- to 8-fold) in rats. These renal effects were reversible within 9 days after removal of the drug. These effects preceded later occurring changes in renal morphology (papillary degeneration and necrosis). There was no evidence of glomerular damage, proximal tubule degeneration or necrosis or tubulointerstitial nephritis at the light microscopic level. Other indices of overall renal function (glomerular filtration rate, electrolyte and glucose excretion) were unaffected. Examination in situ of microperfused proximal tubules from treated rats revealed a 68% decrease in the rate of proximal tubule albumin absorption compared to controls (19 +/- 4 vs. 59 +/- 7 pg/min/mm, respectively). Fluid absorption rate and bicarbonate handling by the proximal tubule, along with blood bicarbonate concentrations, pH, PCO2 and PO2, were unaffected by treatment. It was concluded that tenidap caused a rapid, stable and reversible phosphaturia, microalbuminuria and proteinuria in the rat. The proteinuric effects were due to impaired proximal tubule albumin reabsorption that were not associated with other signs of impaired renal function or histological evidence of tubulointerstitial nephritis or proximal tubule/glomerular damage.

Albumins↗
PubMed1989

Prostaglandin E2 production by dispersed canine fundic mucosal cells. Contribution of macrophages and endothelial cells as major sources.

Endogenous prostaglandins (PGs) influence resistance of the gastric mucosa to injury, but the source of PGs is unknown. Using radioimmunoassay, we studied PG production by dispersed canine fundic mucosal cells. PGE2 production, stimulated by bradykinin, epidermal growth factor, zymosan, and calcium ionophore, was greater in the small-cell elutriator fraction (SCEF) than in the medium and large cell fractions, which contained mucous, chief, and parietal cells. Linear density gradients of SCEF cells revealed maximal PGE2 production in cells of light density. Mast, endocrine, and endothelial cells did not account for this PGE2 production. Macrophages, identified by uptake of acetylated-LDL, immunoreactivity with antibodies to the human Ia antigen, and phagocytosis of fluorescent latex particles, were enriched in the SCEF and correlated with PGE2 production in the density gradient. Magnetic separation of cells in the SCEF-ingesting iron particles enriched PGE2 production. Fractions enriched in endothelial cells present in intact capillary fragments, but depleted of macrophages, also produced PGE2. Regulation of PGE2 production differed among cell types. Fibroblasts were easily cultured from submucosa, but were not detected in the SCEF. We conclude that macrophages and capillary endothelial cells are major producers of PGE2 in the canine fundic mucosa.

Animals↗
PubMed1988

Prostanoid inhibition of canine parietal cells: mediation by the inhibitory guanosine triphosphate-binding protein of adenylate cyclase.

We have investigated the mechanisms underlying prostaglandin inhibition of histamine-stimulated parietal cell function. Enzyme-dispersed canine parietal cells were enriched by elutriation. The accumulation of the weak base [14C]aminopyrine was used as an index of parietal cell function and cyclic adenosine monophosphate content was measured by radioimmunoassay. Step density gradients of the elutriator-enriched parietal cell fractions indicated that parietal cells accounted for the histamine stimulation of cyclic adenosine monophosphate production and inhibition by the prostaglandin E analogue Enprostil. Pertussis toxin adenosine diphosphate-ribosylates a subunit with a molecular weight of 41,000, thereby inactivating the inhibitory guanine nucleotide-binding protein of adenylate cyclase. Pertussis toxin treatment of parietal cells in overnight suspension culture was used to determine if inhibitory guanosine triphosphate-binding protein mediated prostanoid inhibition. In control cultured cells, prostaglandin E2 and Enprostil markedly inhibited forskolin- and histamine-stimulated aminopyrine accumulation. In parietal cells treated with pertussis toxin (300 ng/ml) for 18 h, stimulation of parietal cell function by histamine, isobutylmethylxanthine, and forskolin was unaltered compared with control cells, whereas prostaglandin E2 and Enprostil inhibition was markedly reduced. In pertussis toxin-treated cells, histamine-stimulated cyclic adenosine monophosphate generation was unaltered, whereas Enprostil inhibition of histamine-stimulated cyclic adenosine monophosphate production was markedly reduced. Pertussis toxin treatment of membranes from control, but not from pertussis toxin-treated, cells induced the [32P]adenosine diphosphate-ribosylation of a membrane protein with a molecular weight of 41,000, presumably the alpha-subunit of inhibitory guanosine triphosphate-binding protein. We conclude that prostanoids inhibit parietal cell function by receptor-mediated interaction with the inhibitory guanine nucleotide-binding protein of adenylate cyclase.

Adenosine Diphosphate Ribose↗
PubMed1986

Characterization of receptors regulating secretory function in the fundic mucosa.

A model for a present view of the major pathways and receptors mediating function in the canine fundic mucosa is depicted in Figure 1. Gastrin has direct actions on the parietal cell and on the somatostatin cell; action on the parietal cell, but not somatostatin cell, is potentiated by histamine. In contrast, gastrin action on the somatostatin cell is potentiated by beta-adrenergic agonists. The potency of H2 blockers against gastrin may reflect blockage by these inhibitors of the stimulatory (parietal cell), but not the inhibitory (somatostatin cell), component of gastrin action, thus shifting the balance of gastrin effects toward the inhibitory side. The profound effects of H2 antagonists on gastrin action may also reflect an effect mediated by histamine release, but this possibility awaits direct confirmation. Cholinergic pathways also have at least dual sites of action: stimulation of the parietal cell, and blockage of the release of the inhibitory transmitter somatostatin. Anticholinergic agents may therefore have a dual acid inhibitory effect by reducing direct parietal cell stimulation and enhancing somatostatin release. There is little doubt that this model will rapidly evolve, but the concept that the pathways mediating acid secretion both converge in parallel at the parietal cell, and act in series to cause the release of paracrine transmitters, is attractive and likely to persist.

Animals↗
PubMed1983

Transepithelial transport in cell culture: bioenergetics of Na-, D-glucose-coupled transport.

The renal cell line LLC-PK1 cotransports Na and D-glucose from the apical to the basolateral side of the cell monolayer, and the short-circuit current (Isc) measures the net amount of Na transported. Under conditions of maximal cotransport, the addition of phlorizin or removal of Na reversibly decreased oxygen consumption by one-half. In the absence of glycolytic substrates, alpha-methyl-D-glucoside stimulated Isc and oxygen consumption, although the Isc came to a steady state 50% less than when glycolytic substrates were present. The addition of other aerobic substrates did not increase Isc; however, when non-cotransported glycolytic substrates were introduced the Isc returned to a maximum with an associated fall in oxygen consumption and increased lactate production. Thus, in the absence of glycolytic substrates aerobic ATP formation may be rate-limiting for Na, D-glucose cotransport. For this epithelium glycolysis makes an important contribution to the provision of energy for transport. Oxygen consumption does not correlate well with Isc and is not a good measure of the energy used in transport.

Animals↗
PubMed1983

Regulation of pepsinogen release from canine chief cells in primary monolayer culture.

To study the regulation of pepsinogen secretion by chief cells, we have developed techniques for the isolation, enrichment, and short-term culture of chief cells from canine stomach. The fundic mucosa was enzyme dispersed and chief cells were enriched to a content of about 70% using an elutriator rotor. After 36 h in culture confluent monolayers formed that were highly enriched in chief cells. Carbachol induced a time-dependent release of pepsinogen into the medium, with about a threefold increase in pepsinogen secretion over controls found after 60 min of incubation. Carbachol stimulation of pepsinogen secretion was dose dependent, with 5 microM producing 50% of the maximal response found at a carbachol concentration of 100 microM. Atropine (100 microM) produced a rightward shift of the dose-response curve, indicating the presence of a muscarinic receptor. Dibutyryl cAMP, 8-bromo-cAMP, and forskolin also markedly stimulated pepsinogen secretion. Secretin and vasoactive intestinal peptide (VIP) stimulated pepsinogen secretion, but the response were of smaller magnitude than found with carbachol or the cAMP analogues. The phosphodiesterase inhibitor isobutylmethylxanthine also caused a small stimulation of pepsinogen secretion but did not enhance the response to secretin or VIP. These findings indicate that epithelial monolayers can spontaneously form from isolated canine chief cells and retain functional differentiation evident by a response to stimulation. Canine chief cells in culture possess muscarinic and secretin receptors and respond to cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Potassium metabolism in seawater teleosts. I. The use of 86Rb as a tracer for potassium.

Comparison of the movements of rubidium and potassium between blood and tissues, and between blood and external medium, was undertaken in seawater adapted rainbow trout (Salmo gairdneri) and sculpin (Leptocottus armatus). Qualitative observations suggested that the two ions behaved similarly in exchanges within both fish. More than 90% of an injected dose of both ions disappeared from the blood within 1 h. Complete equilibration of both required about 5 h, and the decrease in blood concentration during the last 4 h followed similar kinetics. After injection and equilibration of 86Rb into trout the specific activity of most tissue pools (c.p.m. 86Rb/microeq tissue K) was close to that of blood (c.p.m. 86Rb/microeq plasma K). Skeletal muscle was the sole exception; its specific activity was less than 15% that of plasma even 4-5 h after injection. Injection of ouabain into trout caused cells to lose both 86Rb and K at similar rates. The same thing occurred when [K] in the external medium was raised abruptly. Exchanges of the two ions between blood and the external medium were also similar. Both ions were extruded and taken up rapidly across the gills. Double-labelling (86Rb and 42K fluxes measured simultaneously) showed that JK/JRb = 1.27 for both influx and efflux in trout. The same value was obtained for effluxes in sculpin. Exposing sculpin to seawater lacking Na and K caused both 42K and 86Rb efflux to fall by 75-80%; 86Rb efflux decreased similarly in trout. Alkali metal-free sea water also caused the voltage across the trout gill to change from +10 mV to -20 mV, and in the sculpin from +25 mV to -25 mV. Addition of either Rb or K to the ion-deficient medium partially repolarized the gill in both fish. Repolarization was slightly greater after K repletion than after Rb repletion. These observations suggest that 86Rb is an adequate tracer for potassium movement in seawater-adapted fish. The gills of trout and sculpin are a little more permeable to K than to Rb, and 86Rb fluxes must be multiplied by 1.3 to provide accurate estimates of transbranchial K movement. The quantitative relationship between JK and JRb within the animal was not established, but some data suggest that cell membranes in fish, like the gills, are somewhat more permeable to K than to Rb.

Animals↗
PubMed1983

Potassium metabolism in seawater teleosts: II. Evidence for active potassium extrusion across the gill.

Unidirectional K-fluxes were estimated in unanaesthetized trout and sculpin and in anaesthetized sculpin from observed 86Rb movement (JK = 1.3 JRb). In all three groups efflux exceeded influx; Jo/Jin was 2-3. The values predicted by the flux ratio equation were 0.5 for trout and 1.0 for sculpin, so active K-extrusion is indicated. The results also show that more than one half of the total influx must be ingested with food rather than passing across the gills. Flux data show that the gills are more permeable to K+ than to Na+, PK/PNa was 5.4 in trout and 2.6 in sculpin. Changes in K-concentration in the external medium did not appear to affect efflux; there was no exchange component in the total fluxes. When both Na+ and K+ were omitted from the bathing solution, efflux decreased to about 15% of the normal seawater value. This is more than would be expected if the flux were purely diffusive and supports the conclusion that extrusion contains an active component. Repletion of the ion-deficient medium with K+ (alone) increased K-efflux. However, it also repolarized the gill and increased plasma [K+], and the flux change could be accounted for by the augmented driving force; i.e. it was diffusive. The additional plasma K came from the intracellular compartment, rather than an augmented influx from the medium.

Animals↗