Effects of Intrathecal Glutamatergic Drugs on Locomotion. II. NMDA and AP-5 in Intact and Late Spinal Cats

2003 ◽  
Vol 90 (2) ◽  
pp. 1027-1045 ◽  
Author(s):  
Nathalie Giroux ◽  
Connie Chau ◽  
Hugues Barbeau ◽  
Tomás A. Reader ◽  
Serge Rossignol
Keyword(s):  
Excitatory Amino Acids ◽  
Early Stage ◽  
Pattern Generator ◽  
Major Effect ◽  
Low Doses ◽  
Receptor Stimulation ◽  
Locomotor Pattern ◽  
Weight Support ◽  
Spontaneous Expression ◽  
Nmda Receptor Blocker

In a previous article, we have shown that, in cats, intrathecal injections of N-methyl-d-aspartate (NMDA) in the first few days after spinalization at T13 do not induce locomotion as in many other spinal preparations. This is in contrast to alpha-2 noradrenergic receptor stimulation, which can trigger locomotion at this early stage. However, it is known that spinal cats do recover spontaneous locomotion in the absence of descending noradrenergic pathways and that the spinal pattern generator must then depend on other neurotransmitters still present in the cord such as excitatory amino acids. In the present paper, therefore we look at the effects of intrathecal NMDA, a glutamatergic agonist, and 2-amino-5-phosphonovaleric acid (AP-5), an NMDA receptor blocker, in both intact and late spinal cats. Low doses of NMDA had no major effect on the locomotor pattern in both intact and late spinal cats. Larger doses of NMDA in the chronic spinal cat initially produced an increase in the general excitability followed by more regular locomotion. AP-5 in intact cats caused a decrease in the amplitude of the flexion reflex and induced a bilateral foot drag as well as some decrease in weight support but it did not prevent locomotion. However, in late spinal cats, the same dose of AP-5 blocked locomotion completely. These results indicate that NMDA receptors may be critical for the spontaneous expression of spinal locomotion. It is proposed that the basic locomotor rhythmicity in cats is NMDA-dependent and that normally this glutamatergic mechanism is modulated by other neurotransmitters, such as 5-HT and NA.

Investigation of the role of microtubules in protein secretion from lactating mouse mammary epithelial cells

1992 ◽  
Vol 102 (2) ◽  
pp. 239-247 ◽  
Author(s):  
M.E. Rennison ◽  
S.E. Handel ◽  
C.J. Wilde ◽  
R.D. Burgoyne
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Protein Secretion ◽  
Secretory Pathway ◽  
Mammary Epithelial Cells ◽  
Early Stage ◽  
Major Effect ◽  
Vesicle Transport ◽  
Mammary Epithelial ◽  
Mammary Cells

Disruption of microtubules has been shown to reduce protein secretion from lactating mammary epithelial cells. To investigate the involvement of microtubules in the secretory pathway in these cells we have examined the effect of nocodazole on protein secretion from mammary epithelial cells derived from the lactating mouse. Mouse mammary cells have extensive microtubule networks and 85% of their tubulin was in a polymeric form. Treatment with 1 micrograms/ml nocodazole converted most of the tubulin into a soluble form. In a continuous labelling protocol it was found that nocodazole did not interfere with protein synthesis but over a 5 h period secretion was markedly inhibited. To determine whether the inhibition was at the level of early or late stages of the secretory pathway mammary cells were pulse-labelled for 1 h to label protein throughout the secretory pathway before nocodazole treatment. When secretion was subsequently assayed it was found to be slower and only partially inhibited. These findings suggest that the major effect of nocodazole is on an early stage of the secretory pathway and that microtubules normally facilitate vesicle transport to the plasma membrane. An involvement of microtubules in vesicle transport to the plasma membrane is consistent with an observed accumulation of casein vesicles in nocodazole-treated cells. Exocytosis stimulated by the calcium ionophore ionomycin was unaffected by nocodazole treatment. We conclude from these results that the major effect of nocodazole is at an early stage of the secretory pathway, one possible target being casein vesicle biogenesis in the trans-Golgi network.

Comparison of the Effect of Intrathecal Administration of Clonidine and Yohimbine on the Locomotion of Intact and Spinal Cats

2001 ◽  
Vol 85 (6) ◽  
pp. 2516-2536 ◽  
Author(s):  
Nathalie Giroux ◽  
Tomás A. Reader ◽  
Serge Rossignol
Keyword(s):  
Acid Methyl Ester ◽  
Intrathecal Administration ◽  
Cycle Duration ◽  
Descending Pathways ◽  
Step Cycle ◽  
Locomotor Pattern ◽  
Before And After ◽  
Spontaneous Expression ◽  
High Doses ◽  
Treadmill Locomotion

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate “fictive” locomotion in immobilized acutely spinalized cats and α2-noradrenergic agonists, such as 2,6,-dichloro- N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the α2 agonist, clonidine, and the antagonist (16α, 17α)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L3–L4before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50–150 μg/100 μl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800–1600 μg/100 μl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 μg/100 μl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

Limb Movements During Embryonic Development in the Chick: Evidence for a Continuum in Limb Motor Control Antecedent to Locomotion

2005 ◽  
Vol 94 (6) ◽  
pp. 4401-4411 ◽  
Author(s):  
Nina S. Bradley ◽  
Dhara Solanki ◽  
Dawn Zhao
Keyword(s):  
Motor Control ◽  
Motor Behavior ◽  
Pattern Generator ◽  
Limb Movements ◽  
Locomotor Pattern ◽  
Developmental Progression ◽  
Critical Phase ◽  
Emg Patterns ◽  
First Descriptions ◽  
Time Point

New imaging technologies are revealing ever-greater details of motor behavior in fetuses for clinical diagnosis and treatment. Understanding the form, mechanisms, and significance of fetal behavior will maximize imaging applications. The chick is readily available for experimentation throughout embryogenesis, making it an excellent model for this purpose. Yet in 40 yr since Hamburger and colleagues described chick embryonic behavior, we have not determined if motility belongs to a developmental continuum fundamental to posthatching behavior. This study examined kinematics and synchronized electromyography (EMG) during spontaneous limb movements in chicks at four time points between embryonic days (E) 9–18. We report that coordinated kinematic and/or EMG patterns were expressed at each time point. Variability observed in knee and ankle excursions at E15–E18 sorted into distinct in-phase and out-of-phase patterns. EMG patterns did not directly account for out-of-phase patterns, indicating study of movement biomechanics will be critical to fully understand motor control in the embryo. We also provide the first descriptions of 2- to 10-Hz limb movements emerging E15–E18 and a shift from in-phase to out-of-phase interlimb coordination E9–E18. Our findings revealed that coordinated limb movements persist across development and suggest they belong to a developmental continuum for locomotion. Limb patterns were consistent with the half center model for a locomotor pattern generator. Achievement of these patterns by E9 may thus indicate the embryo has completed a critical phase beyond which developmental progression may be less vulnerable to experimental perturbations or prenatal events.

A kinematic comparison of the locomotor pattern of horses sedated with detomidine alone and in combination with low doses of butorphanol

2019 ◽  
Vol 51 (6) ◽  
pp. 825-830 ◽  
Author(s):  
M. A. Frigerio ◽  
D. Gómez Cisneros ◽  
I. Santiago Llorente ◽  
G. Manso‐Díaz ◽  
J. López‐Sanromán
Keyword(s):  
Low Doses ◽  
Locomotor Pattern

scholarly journals Systematic Review of Appropriate Robotic Intervention for Gait Function in Subacute Stroke Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ji-Eun Cho ◽  
Jun Sang Yoo ◽  
Kyoung Eun Kim ◽  
Sung Tae Cho ◽  
Woo Seok Jang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Early Stage ◽  
Onset Time ◽  
Gait Training ◽  
Walking Ability ◽  
Stroke Patients ◽  
Related Function ◽  
Subacute Stroke ◽  
Weight Support ◽  
Gait Function

The purpose of this study was to critically evaluate the effects of robot-assisted gait training (RAGT) on gait-related function in patients with acute/subacute stroke. We conducted a systematic review of randomized controlled trials published between May 2012 and April 2016. This search included 334 articles (Cochrane, 51 articles; Embase, 175 articles; PubMed, 108 articles). Based on the inclusion and exclusion criteria, 7 studies were selected for this review. We performed a quality evaluation using the PEDro scale. In this review, 3 studies used an exoskeletal robot, and 4 studies used an end-effector robot as interventions. As a result, RAGT was found to be effective in improving walking ability in subacute stroke patients. Significant improvements in gait speed, functional ambulatory category, and Rivermead mobility index were found with RAGT compared with conventional physical therapy(p<0.05). Therefore, aggressive weight support and gait training at an early stage using a robotic device are helpful, and robotic intervention should be applied according to the patient’s functional level and onset time of stroke.

Different effects of histamine H1 and H2 stimulation on left ventricular contractility in pigs

1995 ◽  
Vol 269 (3) ◽  
pp. H959-H964
Author(s):  
D. J. Cooper ◽  
R. R. Schellenberg ◽  
K. R. Walley
Keyword(s):  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Hill Coefficient ◽  
Maximum Effect ◽  
Low Doses ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Receptor Stimulation ◽  
H2 Antagonist

Histamine decreases ventricular contractility in some settings but increases it in others. To better understand these apparently discrepant results, we measured hemodynamics and left ventricular pressure (Millar catheter) and volume (ultrasonic crystals) in atrially paced, alpha- and beta-antagonist-treated pigs. Histamine was infused (0.5-10 micrograms.kg-1.min-1) before and after H2-antagonist (ranitidine) pretreatment. Changes in left ventricular contractile function were measured as shift of the end-systolic pressure-volume relationship (delta ESPVR) at a pressure of 100 mmHg. We found that at low doses (0.5 and 1 micrograms.kg-1.min-1), histamine significantly decreased delta ESPVR (-1.1 +/- 1.4 ml, P < 0.05) after H2-antagonist pretreatment. At doses above 1 micrograms.kg-1.min-1, histamine increased contractility in a dose-response fashion [maximum effect: 5.1 +/- 3.3 ml, dose resulting in 50% effect (ED50): 0.75 +/- 1.79 micrograms.kg-1.min-1] that was best described using a Hill coefficient of 2. Ranitidine increased the ED50 by approximately one order of magnitude (0.75 +/- 1.79 to 9.50 +/- 2.60 micrograms.kg-1.min-1, P < 0.05). We conclude that in vivo, at higher doses, histamine increases left ventricular contractility via H2-receptor stimulation, whereas at low doses histamine decreases left ventricular contractility, probably via H1-receptor stimulation.

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