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Single Stimulus (single + stimulus)
Selected AbstractsActively regulating bioengineered tissue and organ formationORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2005DJ Mooney Structured Abstract Authors ,, Mooney DJ, Boontheekul T, Chen R, Leach K Objectives ,, Describe current and future approaches to tissue engineering, specifically in the area of bone regeneration. These approaches will allow one to actively regulate the cellular populations participating in this process. Design ,, Many approaches to actively regulate cellular phenotype are under exploration, and these typically exploit known signal transduction pathways via presentation of specific receptor-binding ligands, and may also deliver mechanical information via the physical bridge formed by the receptor-ligand interactions. Cellular gene expression may also be directly modulated utilizing gene therapy approaches to control tissue regeneration. Conclusions ,, Significant progress has been made to date in bone regeneration using inductive molecules and transplanted cells, and FDA approved therapies have resulted. While approaches to date have focused on delivery of single stimuli (e.g. one growth factor), future efforts will likely attempt to more closely mimic developmental processes by the delivery of multiple inputs to the cells in spatially and temporally regulated fashions. [source] Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with AgingEPILEPSIA, Issue 2000Ryosuke Hanaya Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source] P1 Regionalisation of the brain as an evolutionarily conserved developmental mechanism.JOURNAL OF ANATOMY, Issue 1-2 2001E. GALE Comparative studies of chordate neural connectivity and gene families have provided evidence for evolutionary conservation of the patterning mechanisms in brain development (review Holland & Holland, Curr. Opin. Neurobiol.9, 1999). Based on expression patterns of ascidian and amphioxus homologues of the Otx gene and the Hox1 gene and of the ascidian Pax-2/5/8, the chordate brain has been suggested to have tripartite development (Wada et al., Development125, 1998; Kozmik et al., Development126, 1999). Primitively, the chordates have regions homologous to the vertebrate forebrain, anterior midbrain and posterior hindbrain while the posterior midbrain/anterior hindbrain region seems to be a vertebrate innovation. The extent of the homologies within each of these regions between the vertebrates and their ancestors is not fully determined but the similarity of Hox gene expression patterns suggests organisational constants over evolutionary time within the posterior hindbrain region. Identification of the posterior hindbrain region as a developmental unit in vertebrates is demonstrated in the retinoid-deficient quail. Embryos laid by quails fed a retinoid-deficient diet have no posterior hindbrain while the anterior hindbrain is specified normally. Through DiI cell lineage tracing and a temporal analysis of gene expression characteristic of this region (Krox-20, Hoxb-1, mafB, and fgf3), we have followed the development of this region of cells. From the initial formation of the neural plate phenotype in the retinoid-deficient quail, there is no evidence of a posterior hindbrain. This region is never specified and all the cells of the hindbrain participate in an anterior hindbrain fate. A single retinoid injection in ovo during early development completely rescues the posterior hindbrain ensuring that the phenotype was the result of a single stimulus. Therefore cells from the posterior hindbrain respond in a coordinated regional manner to the presence or absence of a single gene inducer, retinoic acid. We present evidence of regionalisation of the vertebrate head that is up stream of segment specification. In combination with data from amphioxus and ascidians, this may represent a common mechanism for head development throughout chordate evolution. Interestingly, regional deletion with enlargement of the adjacent region is very reminiscent of the gap gene phenotype in Drosophila. It would be disregarding millions of years of divergent evolution to suggest that vitamin A is identical to a Drosophila gap gene inducer; nevertheless this data supports the hypothesis of common underlying regulation of axial regionalisation and gene hierarchies. [source] Dopamine agonists restore cortical plasticity in patients with idiopathic restless legs syndrome,MOVEMENT DISORDERS, Issue 5 2009Vincenzo Rizzo MD Abstract In the present work, we aimed at assessing whether patients with idiopathic restless legs syndrome (RLS) showed alterations of sensory-motor plasticity, an indirect probe for motor learning, within the motor cortex (M1). Previous findings suggest that learning in human M1 occurs through LTP-like mechanisms. To test our hypothesis, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Twelve patients with idiopathic RLS and 10 age- and sex-matched control subjects were recruited. PAS protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli), paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of the electrical stimulus. Corticospinal excitability recorded in APB muscle, as indexed by MEP obtained after single stimulus, was tested before and up to 30 minutes after PAS protocol. Eight of 12 patients were studied before and after 4 weeks of dopaminergic treatment. PAS protocol increased significantly corticospinal excitability as long as 30 minutes in healthy subjects. On the contrary, PAS protocol did not change the amplitude of MEPs in patients with idiopathic RLS without treatment. PAS associative plasticity was restored after 4 weeks of dopaminergic treatment. Our data demonstrated that associative sensory-motor plasticity, an indirect probe for motor learning, is impaired in idiopathic RLS patients but may be reverted to normal after dopaminergic treatment. © 2008 Movement Disorder Society [source] Somatosensory disinhibition in dystoniaMOVEMENT DISORDERS, Issue 4 2001Emma Frasson MD Abstract Despite the fact that somatosensory processing is inherently dependent on inhibitory functions, only excitatory aspects of the somatosensory feedback have so far been assessed in dystonic patients. We studied the recovery functions of spinal N13, brainstem P14, parietal N20, P27, and frontal N30 somatosensory evoked potentials (SEPs) after paired median nerve stimulation in 10 patients with dystonia and in 10 normal subjects. The recovery functions were assessed (conditioning stimulus: S1; test stimulus: S2) at interstimuls intervals (ISIs) of 5, 20, and 40 ms. SEPs evoked by S2 were calculated by subtracting the SEPs of the S1 only response from the SEPs of the response to the paired stimuli (S1 + S2), and their amplitudes were compared with those of the control response (S1) at each ISI considered. This ratio, (S2/S1)*100, investigates changes in the excitability of the somatosensory system. No significant difference was found in SEP amplitudes for single stimulus (S1) between dystonic patients and normal subjects. The (S2/S1)*100 ratio at the ISI of 5 ms did not significantly differ between dystonic patients and normal subjects, but at ISIs of 20 and 40 ms, this ratio was significantly higher in patients than in normals for spinal N13 and cortical N20, P27, N30 SEPs. These findings suggest that in dystonia there is an impaired inhibition at spinal and cortical levels of the somatosensory system which would lead to an abnormal sensory assistance to the ongoing motor programs, ultimately resulting in the motor abnormalities present in this disease. © 2001 Movement Disorder Society. [source] The Defibrillation Efficacy of High Frequency Alternating Current Sinusoidal Waveforms in Guinea PigsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2p1 2003SCOTT J. ROBERTS ROBERTS, S.J., et al.: The Defibrillation Efficacy of High Frequency Alternating Current Sinusoidal Waveforms in Guinea Pigs. There have been few basic studies of alternating current (AC) defibrillation, despite growing interest in the ability of AC to terminate or alter ongoing fibrillation. Based on fibrillation threshold testing, it has been suggested that cardiac tissue is most sensitive to long duration, low strength AC stimulation at around 50 Hz. This has not been directly tested for defibrillation. Two subcutaneous electrodes were placed 40 mm apart on opposing aspects of the guinea pig thorax. Seven seconds were allowed to elapse between fibrillation initiation and defibrillation. The tested waveforms were at 50, 100, 200, 500, and 1000 Hz with 2, 4, 8, 16, and 32-cycles. The efficacy of every waveform was measured using a single stimulus in a large population of animals. Forty-one guinea pigs were used in the fixed energy group. Thirty-three guinea pigs were used in the fixed amplitude group with additional 1-cycle waveforms tested. The 200-Hz and the 2-cycle waveforms were significantly more efficacious than those at other frequencies(P < 0.02)and other durations(P < 0.001). The 50-Hz waveforms were the least successful. Amplitude, not duration or energy, was the determinate of efficacy for 2-cycle (the most efficacious) waveforms. Unlike low strength stimulation, defibrillation strength stimuli are most effective with high frequency (200 Hz) pulses (2 cycles). (PACE 2003; 26[Pt. I]:599,604) [source] High cortical spreading depression susceptibility and migraine-associated symptoms in Cav2.1 S218L miceANNALS OF NEUROLOGY, Issue 1 2010Arn M. J. M. van den Maagdenberg PhD Objective The CACNA1A gene encodes the pore-forming subunit of neuronal CaV2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma. Methods We introduced the S218L mutation into the mouse Cacna1a gene and studied the mechanisms for the S218L syndrome by analyzing the phenotypic, molecular, and electrophysiological consequences. Results Cacna1aS218L mice faithfully mimic the associated clinical features of the human S218L syndrome. S218L neurons exhibit a gene dosage,dependent negative shift in voltage dependence of CaV2.1 channel activation, resulting in enhanced neurotransmitter release at the neuromuscular junction. Cacna1aS218L mice also display an exquisite sensitivity to cortical spreading depression (CSD), with a vastly reduced triggering threshold, an increased propagation velocity, and frequently multiple CSD events after a single stimulus. In contrast, mice bearing the R192Q CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus. Interpretation The particularly low CSD threshold and the strong tendency to respond with multiple CSD events make the S218L cortex highly vulnerable to weak stimuli and may provide a mechanistic basis for the dramatic phenotype seen in S218L mice and patients. Thus, the S218L mouse model may prove a valuable tool to further elucidate mechanisms underlying migraine, seizures, ataxia, and trauma-triggered cerebral edema. ANN NEUROL 2010;67:85,98 [source] ,1D -Adrenoceptors mediate nerve and agonist-evoked contractions in mouse vas deferens: evidence obtained from knockout technologyAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2-3 2008S. Bexis Summary 1 It has been demonstrated that nerve-evoked contractions of the rat vas deferens involve ,1D -adrenoceptors. Definitive evidence for a similar ,1D -adrenoceptor-mediated response in mouse vas deferens has been more difficult to obtain. In this study, we have used ,1D -adrenoceptor knockout (,1D -KO) mice to aid in the pharmacological characterization. 2 Mouse whole vas deferens was stimulated with a single pulse every 5 min. Once a stable response had been obtained, vehicle or antagonist was administered cumulatively at 5-min intervals and a response to stimulation obtained 5 min later. Cumulative concentration-response curves were also obtained for noradrenaline. 3 In vas deferens from ,1D -KO mice, the contractile response to low concentrations of noradrenaline and the contractile response to a single stimulus were significantly reduced as compared to wild type (WT). 4 The ,1D -adrenoceptor selective antagonist, BMY 7378, produced a concentration-dependent inhibition of single pulse-evoked contractions of vas deferens from WT and ,1D -KO mice. BMY 7378 was significantly less potent in inhibiting stimulation-evoked contractions in vas deferens from ,1D -KO mice. 5 It is concluded that ,1D -adrenoceptors mediate a component of nerve- and agonist-evoked contractions of the vas deferens of WT mice. [source] | ||||||||||