-
Neuroscience Dec 2016In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a...
In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions.
Topics: Animals; Cold Temperature; Decerebrate State; Functional Laterality; Gray Matter; Microelectrodes; Muscle, Skeletal; Neural Pathways; Neurons; Postural Balance; Rabbits; Reflex; Spinal Cord; Spinal Cord Injuries
PubMed: 27702647
DOI: 10.1016/j.neuroscience.2016.09.043 -
American Journal of Physiology.... Aug 2014The exercise pressor reflex is greater in rats with ligated femoral arteries than it is in rats with freely perfused femoral arteries. The exaggerated reflex in rats...
The exercise pressor reflex is greater in rats with ligated femoral arteries than it is in rats with freely perfused femoral arteries. The exaggerated reflex in rats with ligated arteries is attenuated by stimulation of μ-opioid and δ-opioid receptors on the peripheral endings of thin-fiber muscle afferents. The effect of stimulation of κ-opioid receptors on the exercise pressor reflex is unknown. We tested the hypothesis that stimulation of κ-opioid receptors attenuates the exercise pressor reflex in rats with ligated, but not freely perfused, femoral arteries. The pressor responses to static contraction were compared before and after femoral arterial or intrathecal injection of the κ-opioid receptor agonist U62066 (1, 10, and 100 μg). Femoral arterial injection of U62066 did not attenuate the pressor responses to contraction in either group of rats. Likewise, intrathecal injection of U62066 did not attenuate the pressor response to contraction in rats with freely perfused femoral arteries. In contrast, intrathecal injection of 10 and 100 μg of U62066 attenuated the pressor response to contraction in rats with ligated femoral arteries, an effect that was blocked by prior intrathecal injection of the κ-opioid receptor antagonist nor-binaltorphimine. In rats with ligated femoral arteries, the pressor response to stimulation of peripheral chemoreceptors by sodium cyanide was not changed by intrathecal U62066 injections, indicating that these injections had no direct effect on the sympathetic outflow. We conclude that stimulation of spinal, but not peripheral, κ-opioid receptors attenuates the exaggerated exercise pressor reflex in rats with ligated femoral arteries.
Topics: Animals; Decerebrate State; Femoral Artery; Injections, Intra-Arterial; Injections, Spinal; Ligation; Male; Models, Animal; Naltrexone; Peripheral Nerves; Physical Conditioning, Animal; Pressoreceptors; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Spinal Nerves
PubMed: 24920732
DOI: 10.1152/ajpregu.00156.2014 -
Journal of Applied Physiology... Dec 2015In healthy humans, tests of the hypothesis that lactic acid, PGE2, or ATP plays a role in evoking the exercise pressor reflex proved controversial. The findings in...
In healthy humans, tests of the hypothesis that lactic acid, PGE2, or ATP plays a role in evoking the exercise pressor reflex proved controversial. The findings in humans resembled ours in decerebrate rats that individual blockade of the receptors to lactic acid, PGE2, and ATP had only small effects on the exercise pressor reflex provided that the muscles were freely perfused. This similarity between humans and rats prompted us to test the hypothesis that in rats with freely perfused muscles combined receptor blockade is required to attenuate the exercise pressor reflex. We first compared the reflex before and after injecting either PPADS (10 mg/kg), a P2X receptor antagonist, APETx2 (100 μg/kg), an activating acid-sensing ion channel 3 (ASIC) channel antagonist, or L161982 (2 μg/kg), an EP4 receptor antagonist, into the arterial supply of the hindlimb of decerebrated rats. We then examined the effects of combined blockade of P2X receptors, ASIC3 channels, and EP4 receptors on the exercise pressor reflex using the same doses, intra-arterial route, and time course of antagonist injections as those used for individual blockade. We found that neither PPADS (n = 5), APETx2 (n = 6), nor L161982 (n = 6) attenuated the reflex. In contrast, combined blockade of these receptors (n = 7) attenuated the peak (↓27%, P < 0.019) and integrated (↓48%, P < 0.004) pressor components of the reflex. Combined blockade injected intravenously had no effect on the reflex. We conclude that combined blockade of P2X receptors, ASIC3 channels, and EP4 receptors on the endings of thin fiber muscle afferents is required to attenuate the exercise pressor reflex in rats with freely perfused hindlimbs.
Topics: Acid Sensing Ion Channels; Animals; Blood Pressure; Cnidarian Venoms; Decerebrate State; Hindlimb; Muscle, Skeletal; Neurons, Afferent; Physical Exertion; Purinergic P2X Receptor Antagonists; Pyridoxal Phosphate; Rats; Receptors, Prostaglandin E, EP4 Subtype; Receptors, Purinergic P2X; Reflex; Thiophenes; Triazoles
PubMed: 26472871
DOI: 10.1152/japplphysiol.00630.2015 -
Journal of Applied Physiology... Oct 2016Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in...
Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade.
Topics: Animals; Baroreflex; Biological Clocks; Blood Pressure; Cats; Central Pattern Generators; Decerebrate State; Feedback, Physiological; Heart Rate; Movement; Sympathetic Nervous System
PubMed: 27539494
DOI: 10.1152/japplphysiol.00299.2016 -
Anesthesiology Sep 2017The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid...
BACKGROUND
The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid concentrations altered the respiratory pattern in the parabrachial nucleus, a pontine region contributing to respiratory pattern generation, and compared these effects with a medullary respiratory site, the pre-Bötzinger complex.
METHODS
Studies were performed in 40 young and 55 adult artificially ventilated, decerebrate rabbits. We identified an area in the parabrachial nucleus where α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjections elicited tachypnea. Two protocols were performed in separate sets of animals. First, bilateral microinjections of the μ-opioid receptor agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (100 μM) into the "tachypneic area" determined the effect of maximal μ-opioid receptor activation. Second, respiratory rate was decreased with continuous IV infusions of remifentanil. The opioid antagonist naloxone (1 mM) was then microinjected bilaterally into the "tachypneic area" of the parabrachial nucleus to determine whether the respiratory rate depression could be locally reversed.
RESULTS
Average respiratory rate was 27 ± 10 breaths/min. First, [D-Ala, N-MePhe, Gly-ol]-enkephalin injections decreased respiratory rate by 62 ± 20% in young and 45 ± 26% in adult rabbits (both P < 0.001). Second, during IV remifentanil infusion, bilateral naloxone injections into the "tachypneic area" of the parabrachial nucleus reversed respiratory rate depression from 55 ± 9% to 20 ± 14% in young and from 46 ± 20% to 18 ± 27% in adult rabbits (both P < 0.001). The effects of bilateral [D-Ala, N-MePhe, Gly-ol]-enkephalin injection and IV remifentanil on respiratory phase duration in the "tachypneic area" of the parabrachial nucleus was significantly different from the pre-Bötzinger complex.
CONCLUSIONS
The "tachypneic area" of the parabrachial nucleus is highly sensitive to μ-opioid receptor activation and mediates part of the respiratory rate depression by clinically relevant administration of opioids.
Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Female; Male; Parabrachial Nucleus; Piperidines; Rabbits; Remifentanil; Respiratory Insufficiency; Respiratory Rate
PubMed: 28590302
DOI: 10.1097/ALN.0000000000001719 -
American Journal of Physiology. Heart... May 2016Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral... (Comparative Study)
Comparative Study
Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral arterial disease in which a femoral artery is chronically ligated than it is in rats with freely perfused femoral arteries. The role played by the mechanically sensitive component of the exaggerated exercise pressor reflex in ligated rats is unknown. We tested the hypothesis that the mechano-gated channel inhibitor GsMTx4, a relatively selective inhibitor of mechano-gated Piezo channels, reduces the exercise pressor reflex in decerebrate rats with ligated femoral arteries. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the pressor response to Achilles tendon stretch (a purely mechanical stimulus) but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid (purely metabolic stimuli). Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced both the integrated pressor area (control 535 ± 21, GsMTx4 218 ± 24 mmHg·s; P < 0.01), peak pressor (control 29 ± 2, GsMTx4 14 ± 3 mmHg; P < 0.01), and renal sympathetic nerve responses to electrically induced intermittent hindlimb muscle contraction (a mixed mechanical and metabolic stimulus). The reduction of the integrated pressor area during contraction caused by GsMTx4 was greater in rats with ligated femoral arteries than it was in rats with freely perfused femoral arteries. We conclude that the mechanically sensitive component of the reflex contributes to the exaggerated exercise pressor reflex during intermittent hindlimb muscle contractions in rats with ligated femoral arteries.
Topics: Achilles Tendon; Animals; Chemoreceptor Cells; Decerebrate State; Disease Models, Animal; Electric Stimulation; Femoral Artery; Hindlimb; Injections, Intra-Arterial; Intercellular Signaling Peptides and Proteins; Ion Channels; Ligation; Male; Mechanotransduction, Cellular; Membrane Transport Modulators; Muscle Contraction; Muscle, Skeletal; Peptides; Peripheral Arterial Disease; Rats, Sprague-Dawley; Reflex, Stretch; Spider Venoms; Sympathetic Nervous System; Time Factors
PubMed: 26921442
DOI: 10.1152/ajpheart.00974.2015 -
The Journal of Physiology Jul 2017Ligating the femoral artery of a rat for 72 h, a model for peripheral artery disease, causes an exaggerated exercise pressor reflex in response to muscle contraction....
KEY POINTS
Ligating the femoral artery of a rat for 72 h, a model for peripheral artery disease, causes an exaggerated exercise pressor reflex in response to muscle contraction. Likewise, the hindlimb muscles of rats with ligated femoral arteries show increased levels of reactive oxygen species. Infusion of tiron, a superoxide scavenger, attenuated the exaggerated pressor reflex and reduced reactive oxygen species production in rats with ligated femoral arteries. Conversely, we found no effect of tiron infusion on the pressor reflex in rats with patent femoral arteries. These results suggest a role of reactive oxygen species with respect to causing the exaggerated pressor response to contraction seen in rats with ligated arteries and peripheral artery disease.
ABSTRACT
Contraction of muscle evokes the exercise pressor reflex (EPR), which is expressed partly by increases in heart rate and arterial pressure. Patients with peripheral artery disease (PAD) show an exaggerated EPR, sometimes report pain when walking and are at risk for cardiac arrthymias. Previous research suggested that reactive oxygen species (ROS) mediate the exaggerated EPR associated with PAD. To examine the effects of ROS on the EPR, we infused a superoxide scavenger, tiron, into the superficial epigastric artery of decerebrated rats. In some, we simulated PAD by ligating a femoral artery for 72 h before the experiment. The peak EPR in 'ligated' rats during saline infusion averaged 31 ± 4 mmHg, whereas the peak EPR in these rats during tiron infusion averaged 13 ± 2 mmHg (n = 12; P < 0.001); the attenuating effect of tiron on the EPR was partly reversed when saline was reinfused into the superficial epigastric artery (21 ± 2 mmHg; P < 0.01 vs. tiron). The peak EPR in 'ligated' rats was also attenuated (n = 7; P < 0.01) by infusion of gp91ds-tat, a peptide that blocks the activity of NAD(P)H oxidase. Tiron infusion had no effect on the EPR in rats with patent femoral arteries (n = 9). Western blots showed that the triceps surae muscles of 'ligated' rats expressed more Nox2 and p67phox, which are components of NADPH oxidase, compared to triceps surae muscles of 'freely perfused' rats. Tiron added to muscle homogenates reduced ROS production in vitro. The results of the present study provide further evidence indicating that ROS mediates the exaggeration of EPR in rats with simulated PAD.
Topics: Animals; Femoral Artery; Male; Muscle Contraction; NADH, NADPH Oxidoreductases; NADPH Oxidase 2; Oxidative Stress; Peripheral Arterial Disease; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reflex
PubMed: 28369936
DOI: 10.1113/JP273816 -
Neurology India 2019
Topics: Adolescent; Consciousness; Decerebrate State; Humans; Intracranial Hemorrhages; Locked-In Syndrome; Male; Pons; Pyramidal Tracts
PubMed: 31347575
DOI: 10.4103/0028-3886.263170 -
The European Journal of Neuroscience Jan 2015The dorsal-side-up trunk orientation in standing quadrupeds is maintained by the postural system driven mainly by somatosensory inputs from the limbs. Postural limb...
The dorsal-side-up trunk orientation in standing quadrupeds is maintained by the postural system driven mainly by somatosensory inputs from the limbs. Postural limb reflexes (PLRs) represent a substantial component of this system. Earlier we described spinal neurons presumably contributing to the generation of PLRs. The first aim of the present study was to reveal trends in the distribution of neurons with different parameters of PLR-related activity across the gray matter of the spinal cord. The second aim was to estimate the contribution of PLR-related neurons with different patterns of convergence of sensory inputs from the limbs to stabilization of body orientation in different planes. For this purpose, the head and vertebral column of the decerebrate rabbit were fixed and the hindlimbs were positioned on a platform. Activity of individual neurons from L5 to L6 was recorded during PLRs evoked by lateral tilts of the platform. In addition, the neurons were tested by tilts of the platform under only the ipsilateral or only the contralateral limb, as well as during in-phase tilts of the platforms under both limbs. We found that, across the spinal gray matter, strength of PLR-related neuronal activity and sensory input from the ipsilateral limb decreased in the dorsoventral direction, while strength of the input from the contralateral limb increased. A near linear summation of tilt-related sensory inputs from different limbs was found. Functional roles were proposed for individual neurons. The obtained data present the first characterization of posture-related spinal neurons, forming a basis for studies of postural networks impaired by injury.
Topics: Action Potentials; Animals; Decerebrate State; Electromyography; Female; Gray Matter; Hindlimb; Interneurons; Linear Models; Lumbar Vertebrae; Male; Microelectrodes; Physical Stimulation; Postural Balance; Posture; Rabbits; Reflex; Spinal Cord
PubMed: 25370349
DOI: 10.1111/ejn.12780