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American Journal of Physiology.... Mar 2020The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral...
The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral ventrolateral medulla (RVLM) respond to small-amplitude (<10°) rotations of the body, as in other brain areas that process vestibular signals, although such movements do not affect blood distribution in the body. However, a subsequent experiment in conscious animals showed that few RVLM neurons respond to small-amplitude movements. This study tested the hypothesis that RVLM neurons in conscious animals respond to signals from the vestibular otolith organs elicited by large-amplitude static tilts. The activity of approximately one-third of RVLM neurons whose firing rate was related to the cardiac cycle, and thus likely received baroreceptor inputs, was modulated by vestibular inputs elicited by 40° head-up tilts in conscious cats, but not during 10° sinusoidal rotations in the pitch plane that affected the activity of neurons in brain regions providing inputs to the RVLM. These data suggest the existence of brain circuitry that suppresses vestibular influences on the activity of RVLM neurons and the sympathetic nervous system unless these inputs are physiologically warranted. We also determined that RVLM neurons failed to respond to a light cue signaling the movement, suggesting that feedforward cardiovascular responses do not occur before passive movements that require cardiovascular adjustments.
Topics: Action Potentials; Animals; Cats; Consciousness; Medulla Oblongata; Neurons; Pressoreceptors; Sympathetic Nervous System; Vestibule, Labyrinth
PubMed: 31940234
DOI: 10.1152/ajpregu.00205.2019 -
American Journal of Physiology.... Jan 2020The exercise pressor reflex is composed of two components, namely the muscle mechanoreflex and the muscle metaboreflex. The afferents evoking the two components are...
The exercise pressor reflex is composed of two components, namely the muscle mechanoreflex and the muscle metaboreflex. The afferents evoking the two components are either thinly myelinated (group III) or unmyelinated (group IV); in combination they are termed "thin fiber afferents." The exercise pressor reflex is often studied in unanesthetized, decerebrate rats. However, the relationship between the magnitude of this reflex and the number of thin fiber afferents stimulated by muscle contraction is unknown. This lack of knowledge prompted us to test the hypothesis that the magnitude of the exercise pressor reflex was directly proportional to the amount of muscle mass activated. Muscle mechanoreceptors were stimulated by stretching the calcaneal tendon. Likewise, muscle metaboreceptors were stimulated by injecting lactic acid into the arterial supply of the hindlimb muscles. In addition, both muscle mechanoreceptors and metaboreceptors were stimulated by statically contracting the hindlimb muscles. We found that simultaneous bilateral (both hindlimbs) stimulation of thin fiber afferents with stretch, lactic acid, and static contraction evoked significantly greater pressor responses than did unilateral (one hindlimb) stimulation of these afferents. In addition, the magnitude of the pressor responses to bilateral simultaneous stimulation of thin fiber afferents evoked by stretch, lactic acid, and contraction was not significantly different from the magnitude of the sum of the pressor responses evoked by unilateral stimulation of these afferents by stretch, lactic acid, and contraction. We conclude that the magnitude of the exercise pressor reflex and its two components is dependent on the number of afferents stimulated.
Topics: Animals; Blood Pressure; Decerebrate State; Hindlimb; Male; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 31664869
DOI: 10.1152/ajpregu.00263.2019 -
The Journal of Physiology Aug 2020Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES-evoked locomotor movements differ to some extent from the normal...
KEY POINTS
Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES-evoked locomotor movements differ to some extent from the normal ones. Operation of the locomotor network during ES is unknown. We compared the activity of individual spinal neurons during locomotion initiated by signals from the brainstem and by ES. We demonstrated that the spinal network generating locomotion under each of the two conditions is formed by the same neurons. A part of this network operates similarly under the two conditions, suggesting that it is essential for generation of locomotion under both conditions. Another part of this network operates differently under the two conditions, suggesting that it is responsible for differences in the movement kinematics observed under the two conditions.
ABSTRACT
Locomotion is a vital motor function for both animals and humans. Epidural electrical stimulation (ES) of the spinal cord is used to restore/improve locomotor movements in patients. However, operation of locomotor networks during ES has never been studied. Here we compared the activity of individual spinal neurons recorded in decerebrate cats of either sex during locomotion initiated by supraspinal commands (caused by stimulation of the mesencephalic locomotor region, MLR) and by ES. We found that under both conditions, the same neurons had modulation of their activity related to the locomotor rhythm, suggesting that the network generating locomotion under the two conditions is formed by the same neurons. About 40% of these neurons had stable modulation (i.e. small dispersion of their activity phase in sequential cycles), as well as a similar phase and shape of activity burst in MLR- and ES-evoked locomotor cycles. We suggest that these neurons form a part of the locomotor network that operates similarly under the two conditions, and are critical for generation of locomotion. About 23% of the modulated neurons had stable modulation only during MLR-evoked locomotion. We suggest that these neurons are responsible for some differences in kinematics of MLR- and ES-evoked locomotor movements. Finally, 25% of the modulated neurons had unstable modulation during both MLR- and ES-evoked locomotion. One can assume that these neurons contribute to maintenance of the excitability level of locomotor networks necessary for generation of stepping, or belong to postural networks, activated simultaneously with locomotor networks by both MLR stimulation and ES.
Topics: Animals; Brain Stem; Cats; Decerebrate State; Electric Stimulation; Humans; Locomotion; Mesencephalon; Spinal Cord
PubMed: 32445488
DOI: 10.1113/JP279460 -
BMC Infectious Diseases Jul 2020Pertussis is a highly contagious disease of public health interest caused by the bacterium Bordetella pertussis. Although its incidence has decreased substantially after...
BACKGROUND
Pertussis is a highly contagious disease of public health interest caused by the bacterium Bordetella pertussis. Although its incidence has decreased substantially after the introduction of a vaccination, the burden of the disease remains high. Although the paroxysmal phase is highly disabling, complications are uncommon and more prevalent in children than in adults. The most frequent neurological complication is encephalopathy, but seizures, paresis, paraplegia, ataxias, aphasias, and decerebration postures have also been described. The complication of decerebration postures has not been previously reported in adults.
CASE PRESENTATION
We present a video case of an adult HIV patient with severe coughing paroxysms, post-tussive emesis and syncope, whose workup confirmed the diagnosis of a B. pertussis respiratory infection. During hospitalization, he had fluctuant encephalopathy and post-tussive decerebration postures following paroxysms. He was treated with antibiotic therapy and finally sent home without residual neurological deficits.
CONCLUSION
This case illustrates the biological plausibility of neurologic complications of pertussis in adults, which, albeit rare, can cause important morbidities. Future research should explore whether there are differences in the clinical presentation, risk factors and pathophysiology of the disease among adults or interventions aimed at preventing or treating pertussis encephalopathy.
Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Bordetella pertussis; Brain Diseases; Decerebrate State; HIV; Hospitalization; Humans; Male; Middle Aged; Polymerase Chain Reaction; Risk Factors; Treatment Outcome; Whooping Cough
PubMed: 32615931
DOI: 10.1186/s12879-020-05198-x -
Frontiers in Neurology 2020Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement...
Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.
PubMed: 33391176
DOI: 10.3389/fneur.2020.620817 -
American Journal of Physiology.... Aug 2020Purinergic 2X (P2X) receptors on the endings of group III and IV afferents play a role in evoking the exercise pressor reflex. Particular attention has been paid to P2X3...
Purinergic 2X (P2X) receptors on the endings of group III and IV afferents play a role in evoking the exercise pressor reflex. Particular attention has been paid to P2X3 receptors because their blockade in the periphery attenuated this reflex. In contrast, nothing is known about the role played by P2X receptors in the spinal cord in evoking the exercise pressor reflex in rats. P2X7 receptors, in particular, may be especially important in this regard because they are found in abundance on spinal glial cells and may communicate with neurons to effect reflexes controlling cardiovascular function. Consequently, we investigated the role played by spinal P2X7 receptors in evoking the exercise pressor reflex in decerebrated rats. We found that intrathecal injection of the P2X7 antagonist brilliant blue G (BBG) attenuated the exercise pressor reflex (blood pressure index: 294 ± 112 mmHg·s before vs. 7 ± 32 mmHg·s after; < 0.05). Likewise, intrathecal injection of minocycline, which inhibits microglial cell output, attenuated the reflex. In contrast, intrathecal injection of BBG did not attenuate the pressor response evoked by intracarotid injection of sodium cyanide, a maneuver that stimulated carotid chemoreceptors. Moreover, injections of BBG either into the arterial supply of the contracting hindlimb muscles or into the jugular vein did not attenuate the exercise pressor reflex. Our findings support the hypothesis that P2X7 receptors on microglial cells within the spinal cord play a role in evoking the exercise pressor reflex.
Topics: Animals; Blood Pressure; Decerebrate State; Injections, Spinal; Male; Minocycline; Physical Conditioning, Animal; Purinergic P2X Receptor Antagonists; Rats; Rats, Sprague-Dawley; Reflex; Rosaniline Dyes
PubMed: 32609538
DOI: 10.1152/ajpregu.00093.2020 -
American Journal of Physiology. Heart... Jan 2020The role of the acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown, despite the fact that ASIC1a is opened by decreases in pH in the...
The role of the acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown, despite the fact that ASIC1a is opened by decreases in pH in the physiological range. This fact prompted us to test the hypothesis that ASIC1a plays an important role in evoking the exercise pressor reflex in decerebrated rats with freely perfused hindlimb muscles. To test this hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles on the reflex pressor responses to four maneuvers, namely ) static contraction of the triceps surae muscles (i.e., the exercise pressor reflex), ) calcaneal tendon stretch, ) intra-arterial injection of lactic acid, and ) intra-arterial injection of diprotonated phosphate. We found that the 2 ASIC1a blockers, psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 μg/kg), decreased the pressor responses to static contraction as well as the peak pressor responses to injection of lactic acid and diprotonated phosphate. In contrast, neither ASIC1a blocker had any effect on the pressor responses to tendon stretch. Importantly, we found that ASIC1a blockade significantly decreased the pressor response to static contraction after a latency of at least 8 s. Our results support the hypothesis that ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex. The role played by acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex remains unknown. In decerebrated rats with freely perfused femoral arteries, blocking ASIC1a with psalmotoxin-1 or mambalgin-1 significantly attenuated the pressor response to static contraction, lactic acid, and diprotonated phosphate injection but had no effect on the pressor response to stretch. We conclude that ASIC1a plays a key role in evoking the exercise pressor reflex by responding to contraction-induced metabolites, such as protons.
Topics: Acid Sensing Ion Channels; Animals; Autonomic Nervous System; Chemoreceptor Cells; Decerebrate State; Elapid Venoms; Hindlimb; Hydrogen-Ion Concentration; Male; Membrane Transport Modulators; Muscle Contraction; Muscle Spindles; Muscle, Skeletal; Peptides; Rats, Sprague-Dawley; Reflex; Spider Venoms
PubMed: 31675256
DOI: 10.1152/ajpheart.00565.2019 -
Scientific Reports Apr 2024Several neurologic diseases including spinal cord injury, Parkinson's disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions....
Several neurologic diseases including spinal cord injury, Parkinson's disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions. Clinical data indicates that chronic spinal cord stimulation can improve not only motor function but also ability to store urine and control micturition. Decoding the spinal mechanisms that regulate the functioning of detrusor (Detr) and external urethral sphincter (EUS) muscles is essential for effective neuromodulation therapy in patients with disturbances of micturition. In the present work we performed a mapping of Detr and EUS activity by applying epidural electrical stimulation (EES) at different levels of the spinal cord in decerebrated cat model. The study was performed in 5 adult male cats, evoked potentials were generated by EES aiming to recruit various spinal pathways responsible for LUT and hindlimbs control. Recruitment of Detr occurred mainly with stimulation of the lower thoracic and upper lumbar spinal cord (T13-L1 spinal segments). Responses in the EUS, in general, occurred with stimulation of all the studied sites of the spinal cord, however, a pronounced specificity was noted for the lower lumbar/upper sacral sections (L7-S1 spinal segments). These features were confirmed by comparing the normalized values of the slope angles used to approximate the recruitment curve data by the linear regression method. Thus, these findings are in accordance with our previous data obtained in rats and could be used for development of novel site-specific neuromodulation therapeutic approaches.
Topics: Animals; Cats; Male; Spinal Cord; Electric Stimulation; Spinal Cord Stimulation; Urinary Bladder; Decerebrate State; Urinary Tract; Urethra; Urination; Epidural Space
PubMed: 38670988
DOI: 10.1038/s41598-024-54209-3