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PubMed2006

Innate stimuli accentuate end-organ damage by nephrotoxic antibodies via Fc receptor and TLR stimulation and IL-1/TNF-alpha production.

Innate stimuli are well recognized as adjuvants of the systemic immune response. However, their role in driving end-organ disease is less well understood. Whereas the passive transfer of glomerular-targeting Abs alone elicited minimal renal disease, the concomitant delivery of innate stimuli triggered severe nephritis, characterized by proliferative glomerulonephritis with crescent formation, and tubulointerstitial disease. Specifically, stimulating TLR2, TLR3, TLR4, and TLR5 by using peptidoglycan, poly(I:C), LPS, and flagellin, respectively, all could facilitate anti-glomerular Ab-elicited nephritis. In this model, innate and immune triggers synergistically activated several cytokines and chemokines, including IL-1, IL-6, TNF-alpha, and MCP-1, some of which were demonstrated to be absolutely essential for the development of renal disease. Genetic studies revealed that, whereas the innate trigger is dependent on TLR/IL-1R-associated kinase-mediated signaling, the immune component was contingent on FcR-mediated signals. Importantly, infiltrating leukocytes as well as intrinsic glomerular cells may both serve to integrate these diverse signals. Extrapolating to spontaneous immune-mediated nephritis, although the adaptive immune system may be important in generating end-organ targeting Abs, the extent of damage inflicted by these Abs may be heavily dependent on cues from the innate immune system.

Adjuvants, Immunologic↗
PubMed1991

Magnetic stimulation: technical aspects.

When the voltage induced in a measuring coil by different magnetic stimulators was assessed, the strongest stimulus was generated by Cadwell followed by Novametrix, Dantec and then Digitimer. The Cadwell produced a polyphasic pulse, while the other stimulators generated monophasic stimuli. This is the reason that reversing coil polarity does not influence the site of nerve excitation with the Cadwell equipment, but does with the other stimulators. The magnetic method has proved to be most useful for transcranial excitation of the motor cortex. Magnetic stimuli at C7 excite cervical roots submaximally. Electrical stimuli excite cervical roots supermaximally. No advantage was found in the use of small coils for cervical transcutaneous root stimulation. Electrical stimulation (60-85% output) excited lumbar motor roots supramaximally in each healthy subject. However, magnetic stimulation at T12/L1 (100% output) evoked responses in only 8 (Novametrix) and 12 (Cadwell) out of 18 trials without any difference between right and left. The most reliable method for transcutaneous non-invasive excitation of motor roots is electrical stimulation.

Action Potentials↗
PubMed1981

Unit responses of intralaminar thalamus to midbrain and medullary stimulation and effects of conditioning caudate and hippocampal stimuli.

Single units responding to heterotopic somatic stimuli, on extracellular recording in thalamic intralaminar and neighbouring nuclei, also responding to stimulation of the midbrain tegmentum or the medullary magnocellular reticular formation. Consideration of response latencies suggested that some monosynaptic projections from both midbrain and medulla may be received in nuclei centralis lateralis, centrum medianum-parafascicularis complex, and medial ventralis lateralis. Responses to brainstem of nuclei medialis dorsalis, lateralis posterior were of considerably longer latency. There was no correlation between shortness of latency and following-rate of unit responses; the ability of intralaminar neurons to follow rapidly-repeated brainstem stimuli is inferred to be limited by inhibitory processes rather than by synaptic interruptions in the afferent pathway. Conditioning stimuli to caudate nucleus or hippocampus suppressed most intralaminar responses to midbrain stimuli, the shortest-latency responses included, suggesting that inhibitory effects could be exerted at the thalamic level, perhaps directly on the responsive neurone.

Animals↗
PubMed1987

Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation.

Feedback controlled constant force stimuli of 4, 6 and 8 N intensities and of 120 s duration were applied to the receptive fields of cutaneous afferent fibers in the rat's tail. Two types of nociceptive units showed sustained discharges during these stimuli: "polymodal" unmyelinated C-units (MH-C units, N = 18, c.v. 0.5-0.9 m/s) and high-threshold mechanoreceptive A-delta-units (HTM-units, N = 10, c.v. 1.9-11.2 m/s). In addition two classes of sensitive low threshold mechanoreceptors, SA I (N = 6) and SA II (N = 5) units, responded to the prolonged mechanical stimuli. At the onset of a noxious pressure, 11 of the 18 polymodal nociceptors exhibited dynamic responses (lasting about 10 s) which were followed by slowly adapting tonic discharges that lasted for the duration of the stimuli. The remaining polymodal C-fiber units (8/18) did not show dynamic discharges at 4 and 6 N. Phasic and tonic discharges were positively correlated with stimulus strength. The HTM-units encoded stimulation intensity mainly by their dynamic discharges. The tonic discharges of these units displayed faster adaptation rates with stronger mechanical stimuli, i.e. encoding of stimulation intensity became progressively weaker during the tonic phase. The discharges of sensitive SA I and SA II units with A beta axons were not positively correlated with the strength of noxious pressure stimuli. Tonic discharge rates of SA I units were negatively correlated to stimulus strength, whereas SA II units usually stopped firing in the course of a stimulus and became reversibly irresponsive to mechanical stimulation. Possible afferent mechanisms underlying the induction of pain by sustained noxious mechanical stimulation are discussed.

Afferent Pathways↗
PubMed2005

Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation.

Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer) are thought to selectively activate Abeta, Adelta and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs) generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG) preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG) neurons of the spinal dorsal horn, which receive inputs predominantly from C and Adelta fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of approximately 0.8 mA (T5/ T250), whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000) was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Abeta, by 250 Hz stimulation both in Abeta and Adelta, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Abeta and Adelta by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Abeta fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Adelta and Abeta fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Adelta fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three stimulus frequencies.

Animals↗
PubMed1993

Use-dependent fade and two-rate recovery of a naloxone-sensitive inhibition in the cat superior cervical ganglion.

In anaesthetized cats, a short train to the cervical sympathetic trunk (CST), of frequency between 0.5 and 5.0 Hz, inhibited the postganglionic compound action potential (CAP) evoked by a test shock to the CST. When the CST was split into two bundles, the inhibition was obtained both homosynaptically and heterosynaptically. The inhibition was antagonized by naloxone and enhanced by peptidase inhibitors. Leu-enkephalin (ENK), injected into the arterial supply of the superior cervical ganglion (SCG) depressed the CAP. The ENK-evoked inhibition was antagonized by naloxone, enhanced by peptidase inhibitors and was occluded by the train-evoked inhibition. After prolonged stimulation of the CST (5-20 min at 5 Hz), the inhibition produced by a short train was depressed (faded). The fade was greater the longer the stimulation. After 20 min of stimulation the inhibition was absent. At this time the depressant effect of ENK was unchanged. When only one bundle of the split CST was stimulated at 5 Hz for 20 min, only the inhibition produced by that bundle faded, although both bundles converged onto a common set of ganglion cells. Thus, the fade is not due to receptor desensitization but more likely to failure to release the inhibitory mediator by the overstimulated axons. When, after 20 min of 5 Hz stimulation, no further stimuli were applied, the inhibition recovered in 60 min (fast recovery). However, recovery was slower when stimulation lasted longer than 20 min. Recovery took three days when stimulation lasted 80 min (slow recovery). The inhibition was markedly depressed after application of colchicine to the CST three days earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor induces activation and restores respiratory burst activity in monocytes from septic patients.

Monocyte activation in response to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was examined in vitro in septic shock patients. These monocytes exhibited a greater respiratory burst activity than monocytes from healthy subjects; the response to secondary stimulation with bacterial stimuli was attenuated. GM-CSF restored the ability of monocytes to respond appropriately to secondary stimulation. Expression of certain integrin adhesion molecules, L-selectin, and Fcgamma receptors was increased on monocytes of septic shock patients; expression of CD11c was reduced. GM-CSF up-regulated integrin expression and decreased L-selectin, FcgammaRII, and FcgammaRIII expression. Septic patients exhibited greater biologic activity of monocyte tissue factor than did healthy subjects. Priming monocytes with GM-CSF accelerated tissue factor activation following stimulation with lipopolysaccharide and bacterial culture supernatant. Certain parameters of monocyte function may be restored by exposure to GM-CSF. This benefit may be offset by an increase in monocyte procoagulant activity.

Adult↗
PubMed1985

Fusimotor after-effects on responses of primary endings to test dynamic stimuli in cat muscle spindles.

Conditioning stimulation of individual dynamic fusimotor axons, either gamma or beta, leaves after-effects which enhance the responses of primary endings to test stimulation of the same axon applied during slow ramp stretch. These after-effects have a long duration, persisting well over 5 min, but are abolished by stretch of large amplitude. The dynamic after-effects also enhance frequencygrams elicited by low-frequency repetitive stimulation during slow ramp stretch, causing single stimuli to become much more effective. When several dynamic axons to the same spindle are isolated, conditioning stimulation of one leaves an after-effect to test stimulation of itself and of all other dynamic axons. When two dynamic axons are used for conditioning stimulation, facilitation or occlusion can be demonstrated in their interaction, indicating that they converge on the same intrafusal element. Dynamic after-effects persist during background static fusimotor activity of considerable amplitude, suggesting that static and dynamic actions are quite independent. Dynamic after-effects appear to result from residual changes in the bag fibre, probably from a persistent increase in the number of cross-bridges between thick and thin filaments. These after-effects produce a large increase in the response of primary endings to dynamic fusimotor activity and probably have an important functional role.

Action Potentials↗
PubMed2005

Postjunctional modulation by muscarinic M2 receptors of responses to electrical field stimulation of rat detrusor muscle preparations.

1. The aim of the present study was to examine the modulator influence of muscarinic M(2) receptors on responses of rat urinary bladder detrusor muscle evoked by endogenous stimuli, i.e. by stimulation of the bladder innervation. 2. Responses were evoked by electrical field stimulation (EFS; 2-20 Hz, 0.8 ms, 60 V) of isolated strip preparations mounted in organ baths. The tension of the muscle strips was recorded digitally. EFS was performed by applying stimulation with either a short duration (5 s) or a longer duration (to reach peak response; approximately 20 s). 3. Effects of muscarinic receptor antagonists (muscarinic M(1)/M(3) receptor selective: 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP); muscarinic M(2) receptor selective: methoctramine), a beta-adrenergic antagonist (propranolol) and an adenosine receptor antagonist (8-p-sulfophenyltheophylline) were assessed on contractile activity and on poststimulatory relaxations. 4. Low concentrations of methoctramine (10(-8) m) reduced or tended to reduce the EFS-induced contraction, e.g. at 2 Hz by 12% while methoctramine at 10(-7) m had no significant effect. In addition, in the presence of 4-DAMP (10(-9) m), which tended to inhibit contractions at all frequencies (2-20 Hz; -17 to -25%), methoctramine at 10(-8) and 10(-7) m induced a further reduction of the contractile responses (-5 to -10%; 2-20 Hz). 5. The beta-adrenergic receptor antagonist propranolol (10(-6) m) and the adenosine receptor antagonist 8-p-sulfophenyltheophylline (10(-6) m) both increased contractile responses by 9-21% (2-10 Hz, long duration; P < 0.05-0.001) as a consequence of antagonizing relaxatory stimuli. Neither antagonist affected the contractile responses to EFS with the short duration stimulation. Poststimulatory relaxations were reduced by 30-60% (P < 0.05) by propranolol and by 40-60% (P < 0.001) by 8-p-sulfophenyltheophylline, but for 8-p-sulfophenyltheophylline only after stimulation with the short duration. 6. In the presence of methoctramine (10(-7) m), the 8-p-sulfophenyltheophylline-induced increases of the contractile response to long duration EFS were significantly enhanced at 10 Hz (+12 +/- 4%; P < 0.05), whereas no such enhancement of the propranolol inhibitory effect occurred in the presence of methoctramine. However, poststimulatory beta-adrenoceptor-evoked relaxations after short duration EFS were increased by about 35% in the presence of methoctramine, but not those after long duration. 7. Thus, muscarinic M(2) receptor activation inhibits adenosine receptor- and beta-adrenoceptor-evoked relaxations of the rat detrusor muscle. The inhibition occurs via a transient postjunctional mechanism that mainly affects responses with a short latency.

Animals↗
PubMed1985

[Long-term reorganization of the neuronal activity in field 7 of the neocortex in the cat after unilateral section of the visual radiation].

Changes in functional characteristics of area 7 cells were studied in cats under semichronic experimental conditions. The experiments were done in various periods of time after unilateral dissection of visual subcortic-cortical fibres. Neuronal responses to visual, auditory, somatic stimuli and electrical stimulation of primary cortical areas were studied in intact and impaired hemispheres. Reappearing of neuronal sensitivity to stimuli of various sensory modalities was found in the partially isolated neocortex. Both the number of cells with local visual receptive fields and averaged receptive field size of the cells increased slowly after the operation. Some suggestions about the nature of plastic changes developing in neuronal nets of the parietal cortex after impairment of subcortico-cortical connections are made.

Animals↗
PubMed1994

Processing of splanchnic and somatic input in thoracic spinal cord of the rat.

To better understand the spinal transmission of visceral afferent information, we conducted neurophysiological studies of single spinal neurons that receive input from the greater splanchnic nerve (GSN). Extracellular single-neuron recordings were made in the thoracic spinal cord of chloralose-anesthetized, paralyzed, and artificially ventilated rats, some of which had undergone acute spinal transection at C1. Neurons were divided into four classes according to their responses to GSN stimulation: one-burst excitatory, two-burst excitatory, biphasic, and inhibited. We then studied the characteristics of the convergent somatic input to each class of neurons using either natural somatic stimuli or electrical stimulation of the iliohypogastric nerve (IHN). Most splanchnic input was mediated by unmyelinated fibers, whereas somatic input was mediated by both unmyelinated and small myelinated fibers. Most of the neurons exhibited somatic receptive fields, and the majority responded to both innocuous and noxious somatic stimuli. However, a small number could be excited only by GSN stimulation. Although a careful analysis of response characteristics indicated that there was a tendency for neurons to exhibit similar responses to electrical stimulation of the GSN and the IHN, we observed many combinations of somatic and visceral responses. We suggest that visceral afferent activity, in addition to being processed via convergent somatovisceral pathways, may be processed by neurons that convey only visceral information or by neurons in which visceral and somatic information is differentially coded.

Afferent Pathways↗
PubMedDate not supplied

[Measurement of the propagation rate of the summation action potential in the vomeronasal and olfactory nerves of Rana temporaria frogs].

It was shown that summation action potential (AP) in various points of the nerve result from summation AP in various bundles of fibres. The rate of propagation of AP in various bundles may differ rather significantly. Propagation of AP from the site of stimulation takes place with acceleration, which is presumably due to the inhibitory effect of the stimulus at the site of its application (together with the excitatory effect as well). Both nerves exhibit also supernormal phenomenon which reveals itself in the increase of the propagation rate of the second AP during stimulation by paired stimuli.

Action Potentials↗
PubMed1991

Rate-level functions of neurons in the inferior colliculus of cats measured with the use of free-field sound stimuli.

1. The responses as a function of stimulus level of 125 single units in the inferior colliculus of anesthetized cats were studied with the use of free-field acoustic stimuli. 2. The characteristic frequency (CF; frequency at which threshold was lowest) of each unit was determined, and stimuli were presented from one of three speaker positions: 45 degrees contralateral to the midline, midline, and 45 degrees ipsilateral to the midline. 3. For each unit a variety of stimulus levels was presented at CF, and the total spike count was summed for 20 stimuli at each level. If time permitted, a similar series of levels of noise was presented. 4. Four classes of rate-level (RL) functions were observed. Monotonic increases in firing rate were observed in 10% of units stimulated with CF stimuli and 57% of units studied with noise. Nonmonotonic RL functions, for which firing first increased and then declined to less than 50% of the peak level, were observed in 61% of units responding to CF tones and in 10% responding to noise. Plateau functions, with shapes lying between these, accounted for 19% of CF responses and the remaining units excited by noise. Some very complex shapes that could not be categorized into the above groups were seen in the remaining 10% of the units responding to CF stimuli. 5. The RL functions of units studied with both noise and CF tones could belong to different classes; commonly, nonmonotonic RL functions to tones were associated with monotonic RL functions to noise. The noise thresholds averaged 10 dB, some 10-20 dB less sensitive than those to CF stimuli. 6. For the vast majority of both noise and tone responses, stimuli from the contralateral location were more effective than those from the other two positions in terms of a lower threshold, higher peak discharge rate, and, for nonmonotonic units, a lower sound level at which the function became nonmonotonic (turnover point). 7. The turnover points of nonmonotonic functions at any given CF could be spread broadly but, overall, tended to be concentrated between -6 and 44 dB. 8. The dynamic ranges (range of levels over which firing rate increased) were larger for monotonic and plateau functions than for nonmonotonic functions, which had dynamic ranges less than 45 dB. The median dynamic range for units stimulated with CF tones was 20 dB and for noise stimuli, 40 dB.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1990

Sensory neglect in a frog: evidence for early evolution of attentional processes in vertebrates.

Mammalian-like 'sensory neglect' phenomena were elicited in Xenopus laevis by unilateral telencephalic lesion: after damage of the caudal striatum response rate to contralateral water waves was significantly lower than to ipsilateral ones. Response accuracy, however, was not affected. Within 6-8 weeks, animals recovered from neglect of unilateral stimuli; but simultaneous bilateral stimulation revealed an enduring neglect of contralateral stimuli. Latencies during acute neglect were significantly higher than after recovery. These results suggest that the neural mechanisms of selective attention might have evolved earlier than thought so far.

Animals↗
PubMed1987

HA autoreceptor assay with superfused slices of rat brain cortex and electrical stimulation.

Slices of rat brain cortex previously loaded with [3H]histamine ([3H]HA) via de novo synthesis from [3H]histidine released tritiated histamine ([3H]HA) Ca2+ dependently in a superfused system. Both electrical field stimulation and high levels of K+ ions elicited this release. The extent of release depended on stimulation intensity. Rather strong stimuli, either by high frequency or longer stimulation, were required to elicit sufficient HA release for proper assessment of the concentration-dependence of release inhibition by drugs. The system showed marked depletion (less response per pulse) upon long-continued or successive stimulations. HA added to the superfusion medium inhibited the release evoked by stimulation at frequencies up to 10 Hz or with 30 mM K+ but not the release at higher frequencies or with 45 mM K+. The inhibition was mediated by H3 receptors, was concentration-dependent (pD2 = 7.4) and was complete at 10(-6) M. The H2 agonist impromidine antagonized the inhibition competitively (pA2 = 7.1). It is concluded that this assay in a superfusion system with electrical stimulation is suitable for the assessment of H3 receptor activity of drugs.

Animals↗
PubMed1995

Effect of electrical stimulation on gastric electrical activity, motility and emptying.

The aim was to measure the effect of gastric electrical stimulation on the frequency of canine antral pacesetter potentials (PPs), the strength of antral contractions, and the rate of gastric emptying while fasting, after feeding and with pentagastrin stimulation. Four conscious dogs with a stimulating electrode placed 10 cm proximal to the pylorus and recording electrodes and strain gauges placed 7, 5 and 3 cm proximal to the pylorus underwent myoelectric and strain gauge recordings while fasting, after feeding (250 ml 5% dextrose labelled with polyethylene glycol), and during pentagastrin infusion (0.5 micrograms kg-1 min-1) on four separate days. On each day, electrical stimulation was done using one of four stimulation frequencies (0, 6, 30 and 1200 stimuli per minute [s.p.m.]). Stimulation at 6 and 30 s.p.m. increased the fasting and fed PP frequency, whereas 1200 s.p.m. stimulation did not. Feeding decreased the maximum driven frequency, and pentagastrin increased it. Neither the motility index nor the gastric emptying rate were consistently changed by stimulation at any frequency. In conclusion, canine proximal antral stimulation at 6 and 30 s.p.m. sped PP frequency during fasting and after feeding, but stimulation over a wide range of frequencies had little effect on gastric contractions and emptying.

Animals↗