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ENeuro 2019There is evidence that a variety of central and afferent stimuli, including swallowing, can produce phase resetting in the respiratory rhythmicity. Also, there are...
There is evidence that a variety of central and afferent stimuli, including swallowing, can produce phase resetting in the respiratory rhythmicity. Also, there are reports about the intrinsic linkage between locomotion and respiration. However, little is known about the interaction between the central pattern generators (CPGs) for scratching and respiration. The present study aims to examine whether the activation of scratching CPG produces phase resetting of the respiratory rhythm. We employed decerebrate cats to apply brief tactile stimuli to the pinna during the inspiratory-expiratory transition. We observed that those stimuli to the pinna not eliciting fictive scratching did not reset the respiratory rhythm. However, when the pinna stimuli elicited fictive scratching, then the respiratory rhythm exhibited a significant phase resetting. We also found interneurons in the medulla oblongata exhibiting phase resetting related to scratching-CPG episodes. This second finding suggests that this type of resetting involves brainstem components of the respiratory CPG. These results shed new light on the resetting action from a spinal CPG on the respiratory rhythm.
Topics: Animals; Cats; Central Pattern Generators; Decerebrate State; Female; Interneurons; Male; Medulla Oblongata; Periodicity; Reflex; Respiratory Rate; Spinal Cord; Touch Perception
PubMed: 31043462
DOI: 10.1523/ENEURO.0116-19.2019 -
Brain Communications 2020Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a...
Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion to the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate that hindlimb postural asymmetry in rats is induced by a unilateral injury of the hindlimb sensorimotor cortex, and characterize this phenomenon as a model of spinal neuroplasticity underlying asymmetric motor deficits. After cortical lesion, the asymmetry was developed due to the contralesional hindlimb flexion and persisted after decerebration and complete spinal cord transection. The asymmetry induced by the left-side brain injury was eliminated by bilateral lumbar dorsal rhizotomy, but surprisingly, the asymmetry after the right-side brain lesion was resistant to deafferentation. Pancuronium, a curare-mimetic muscle relaxant, abolished the asymmetry after the right-side lesion suggesting its dependence on the efferent drive. The contra- and ipsilesional hindlimbs displayed different musculo-articular resistance to stretch after the left but not right-side injury. The nociceptive withdrawal reflexes evoked by electrical stimulation and recorded with EMG technique were different between the left and right hindlimbs in the spinalized decerebrate rats. On this asymmetric background, a brain injury resulted in greater reflex activation on the contra- versus ipsilesional side; the difference between the limbs was higher after the right-side brain lesion. The unilateral brain injury modified expression of neuroplasticity genes analysed as readout of plastic changes, as well as robustly impaired coordination of their expression within and between the ipsi- and contralesional halves of lumbar spinal cord; the effects were more pronounced after the left side compared to the right-side injury. Our data suggest that changes in the hindlimb posture, resistance to stretch and nociceptive withdrawal reflexes are encoded by neuroplastic processes in lumbar spinal circuits induced by a unilateral brain injury. Two mechanisms, one dependent on and one independent of afferent input may mediate asymmetric hindlimb motor responses. The latter, deafferentation resistant mechanism may be based on sustained muscle contractions which often occur in patients with central lesions and which are not evoked by afferent stimulation. The unusual feature of these mechanisms is their lateralization in the spinal cord.
PubMed: 32954305
DOI: 10.1093/braincomms/fcaa055 -
American Journal of Physiology.... Nov 2019The exercise pressor reflex is initiated by the contraction-induced activation of group III and IV muscle afferents. The reflex is manifested by increases in arterial...
The exercise pressor reflex is initiated by the contraction-induced activation of group III and IV muscle afferents. The reflex is manifested by increases in arterial blood pressure and cardiac output, which, in turn, are generated by increases in the sympathetic outflow to the heart and vasculature and decreases in the vagal outflow to the heart. In previous experiments, we used a pharmacological approach to assess the role played by the acid-sensing ion channel 3 (ASIC3) on group III and IV afferents in evoking the exercise pressor reflex. In the present experiments, we used an alternative approach, namely functional knockout (KO) of the ASIC3 gene, to confirm and extend our previous finding that pharmacological blockade of the ASIC3 had only a small impact on the expression of the exercise pressor reflex when the arterial supply to the contracting hindlimb muscles of rats was patent. Using this alternative approach, we compared the magnitude of the exercise pressor reflex evoked in ASIC3 KO rats with that evoked in their wild-type (WT) counterparts. We found both WT and ASIC3 KO rats displayed similar pressor responses to static contraction (WT, = 10, +12 ± 2 mmHg; KO, = 9, +11 ± 2 mmHg) and calcaneal tendon stretch (WT, = 9, +13 ± 2 mmHg; KO, = 7, +11 ± 2 mmHg). Likewise, both WT and ASIC3 KO displayed similar pressor responses to intra-arterial injection of 12 mM lactic acid (WT, = 9, +14 ± 3 mmHg; KO, = 8, +18 ± 5 mmHg), 24 mM lactic acid (WT, = 9,+24 ± 2 mmHg; KO, = 8, +20 ± 5 mmHg), capsaicin (WT, = 9,+27 ± 5 mmHg; KO, = 10, +29 ± 5 mmHg), and diprotonated phosphate ([Formula: see text]; WT, = 6,+22 ± 3 mmHg; KO, = 6, +32 ± 6 mmHg). We conclude that redundant receptors are responsible for evoking the pressor reflexes arising from group III and IV afferents.
Topics: Acid Sensing Ion Channels; Animals; Decerebrate State; Lower Extremity; Muscle Contraction; Muscle, Skeletal; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 31347922
DOI: 10.1152/ajpregu.00148.2019 -
Frontiers in Neural Circuits 2014Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic...
Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a "hyper-cholinergic" state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.
Topics: Animals; Animals, Newborn; Catheters, Indwelling; Cats; Cholinergic Agonists; Cholinergic Antagonists; Decerebrate State; Electrodes, Implanted; Electromyography; Hindlimb; Locomotion; Lumbar Vertebrae; Periodicity; Rats, Sprague-Dawley; Receptors, Cholinergic; Spinal Cord; Spinal Cord Injuries
PubMed: 25414645
DOI: 10.3389/fncir.2014.00132 -
The Journal of Physiology Feb 2016Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however,...
Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however, about the nature of the mechano-gated channels on the thin fibre muscle afferents that contribute to evoke this reflex, termed the exercise pressor reflex. We determined the effect of GsMTx4, an inhibitor of mechano-gated Piezo channels, on the exercise pressor reflex evoked by intermittent contraction of the triceps surae muscles in decerebrated, unanaesthetized rats. GsMTx4 reduced the pressor, cardioaccelerator and renal sympathetic nerve responses to intermittent contraction but did not reduce the pressor responses to femoral arterial injection of compounds that stimulate the metabolically-sensitive thin fibre muscle afferents. Expression levels of Piezo2 channels were greater than Piezo1 channels in rat dorsal root ganglia. Our findings suggest that mechanically-sensitive Piezo proteins contribute to the generation of the mechanical component of the exercise pressor reflex in rats. Mechanical and metabolic stimuli within contracting skeletal muscles evoke reflex autonomic and cardiovascular adjustments. In cats and rats, gadolinium has been used to investigate the role played by the mechanical component of this reflex, termed the exercise pressor reflex. Gadolinium, however, has poor selectivity for mechano-gated channels and exerts multiple off-target effects. We tested the hypothesis that GsMTX4, a more selective mechano-gated channel inhibitor than gadolinium and a particularly potent inhibitor of mechano-gated Piezo channels, reduced the exercise pressor reflex in decerebrate rats. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 5, GsMTx4: 12 ± 5 mmHg, P < 0.01), cardioaccelerator and renal sympathetic nerve responses to 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. Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 2, GsMTx4: 14 ± 3 mmHg, P < 0.01), cardioaccelerator and renal sympathetic nerve responses to electrically-induced intermittent hindlimb muscle contractions. By contrast, injection of 10 μg of GsMTx4 into the jugular vein had no effect on the pressor, cardioaccelerator, or renal sympathetic nerve responses to contraction. Quantitative RT-PCR and western blot analyses indicated that both Piezo1 and Piezo2 channel isoforms were natively expressed in rat dorsal root ganglia tissue. We conclude that GsMTx4 reduced the exercise pressor reflex in decerebrate rats and that the reduction was attributable, at least in part, to its effect on mechano-gated Piezo channels.
Topics: Achilles Tendon; Animals; Decerebrate State; Ganglia, Spinal; Hindlimb; Intercellular Signaling Peptides and Proteins; Ion Channels; Lung; Male; Muscle, Skeletal; Peptides; Physical Conditioning, Animal; Rats, Sprague-Dawley; Reflex; Spider Venoms
PubMed: 26608396
DOI: 10.1113/JP271714 -
Neuromodulation : Journal of the... Jun 2024Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal...
OBJECTIVES
Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal cord. Using this approach, we have previously shown the selectivity of rat muscle activation during transvertebral stimulation (TS). In this work, we investigated the TS to induce forward stepping of the cat's hindlimbs in comparison with epidural stimulation (ES).
MATERIALS AND METHODS
TS was performed with an electrode placed in the VL3-VL6 vertebrae in five decerebrated cats. ES was performed on the same cats in L5-L7 segments. Kinematic parameters of stepping were recorded in addition to electromyographic activity of musculus (m.) iliopsoas (IP), m. tibialis anterior (TA), and m. gastrocnemius lateralis (GL) of both hindlimbs.
RESULTS
With VL3-VL4 TS, all five animals were capable of bipedal forward stepping, whereas VL5 and VL6 TS led to the forward stepping in 3 of 5 and 1 of 5 animals, respectively. Well-coordinated muscle activity led to a high level of intra- and interlimb coordination. Kinematic parameters of TS-induced stepping were similar to those obtained with ES. The TS of the VL3 vertebra causes the frequency lock with the integer multiple of the stimulation frequency. Similarly to the rat model, TS-evoked muscle responses were site specific. They were minimal during VL3 TS and were maximal during VL4-VL5 TS (IP) and VL5-VL6 TS (TA, GL).
CONCLUSIONS
The obtained results support hypotheses about the location of the central pattern generators in the upper lumbar spinal segments. The proposed approach of electrode placement is surgically easier to perform than is ES. This approach is useful for studying site-specific neuromodulation of the spinal sensorimotor networks and for investigating new strategies of locomotor recovery in animal models.
Topics: Animals; Cats; Decerebrate State; Electromyography; Muscle, Skeletal; Hindlimb; Biomechanical Phenomena; Spinal Cord Stimulation; Electrodes, Implanted; Electric Stimulation; Male; Female; Lumbar Vertebrae
PubMed: 36567242
DOI: 10.1016/j.neurom.2022.11.009 -
American Journal of Physiology. Heart... Oct 2017Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The...
Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function. Changes in mean arterial pressure (MAP) and HR induced by EPR or muscle mechanoreflex (a component of EPR) activation were assessed in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) fed normal chow (NC) or a customized diet containing either SPIR or EPL for 3 wk. SHRs treated with SPIR or EPL had significantly attenuated MAP responses to EPR (NC: 45 ± 7 mmHg, SPIR: 26 ± 4 mmHg, and EPL: 24 ± 5 mmHg, = 0.02) and mechanoreflex (NC: 34 ± 9 mmHg, SPIR: 17 ± 3 mmHg, and EPL: 15 ± 3 mmHg, = 0.03) activation. SHRs treated with SPIR or EPL also showed significantly attenuated HR responses to EPR (NC: 17 ± 3 beats/min, SPIR: 9 ± 1 beats/min, and EPL: 9 ± 2 beats/min, = 0.01) and mechanoreflex (NC: 15 ± 3 beats/min, SPIR: 6 ± 1 beats/min, and EPL: 7 ± 1 beats/min, = 0.01) activation. Wistar-Kyoto rats treated with SPIR did not demonstrate significant differences in MAP or HR responses to EPR or mechanoreflex activation. The data suggest that antagonizing MRs may be an effective strategy for the treatment of EPR overactivity in hypertension. Exaggerated cardiovascular responses to exercise in hypertensive patients are linked with overactive exercise pressor reflexes (EPRs). Administration of low-dose mineralocorticoid receptor antagonists (spironolactone or eplerenone) effectively ameliorates abnormal EPR function in hypertension. Effective treatment of EPR overactivity may reduce the cardiovascular risks associated with physical activity in hypertension.
Topics: Animals; Arterial Pressure; Blood Pressure; Decerebrate State; Eplerenone; Heart Rate; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Muscle, Skeletal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reflex; Spironolactone
PubMed: 28733447
DOI: 10.1152/ajpheart.00155.2017 -
American Journal of Physiology.... Aug 2014The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n =...
The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa.
Topics: Air; Animals; Cats; Decerebrate State; Electromyography; Eructation; Esophageal Sphincter, Lower; Esophageal Sphincter, Upper; Esophagogastric Junction; Mechanoreceptors; Muscle Relaxation; Pressure; Stomach
PubMed: 24970778
DOI: 10.1152/ajpgi.00120.2014 -
Neurourology and Urodynamics Apr 2018To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in...
AIM
To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in vivo-like neural connectivity.
METHODS
Adult male mice were decerebrated and arterially perfused with a carbogenated, Ringer's solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a "pithed" DAPM which has no brainstem or spinal cord control.
RESULTS
Functional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose-dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention-induced activity in the non-noxious range which was associated with pMM.
CONCLUSIONS
This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.
Topics: Animals; Decerebrate State; Electromyography; Female; Male; Mice; Pressure; Urethra; Urinary Bladder; Urination; Urodynamics
PubMed: 29333621
DOI: 10.1002/nau.23471 -
Journal of Orthopaedic Case Reports Apr 2022Isolated cerebral fat embolism syndrome (FES) is a rare complication that occurs within the first 3 days of the initial insult. We report a case of multiple long bone...
INTRODUCTION
Isolated cerebral fat embolism syndrome (FES) is a rare complication that occurs within the first 3 days of the initial insult. We report a case of multiple long bone fractures with isolated cerebral FES, despite undergoing early total care with definitive fixation.
CASE PRESENTATION
A 22-year-old female presented with type IIIA open femur shaft fracture on the right side (AO 32B2), closed femur shaft fracture (AO 32B2), comminuted patella fracture on the left side (AO 34C3), and undisplaced mandible fracture. She had a normal sensorium with a Glasgow Coma Scale (GCS) of E4V5M6. A whole body computed tomography (CT) scan was done to rule out other injuries. All initial scans were normal. After about 6 h in the ICU, she was noticed to have disconjugate gaze and was answering in monosyllables. A repeat CT scan of the brain was normal. The early total care and definitive fixation with titanium intramedullary nails for femur fractures and tension band wiring for patella was done under general anesthesia. On 1st post-operative day (POD), her GCS dropped to E1VTM1. On the 3rd POD, she developed decerebrate rigidity and generalized tonic clonic seizures. Fundoscopic examination showed multiple fat globules along the vessel in the entire field of both eyes. Since there were no other signs of FES in the lungs or on the skin, an MRI brain was done which revealed a hyperintensive starfield pattern on diffusion-weighted images, suggestive of cerebral fat embolism (CFE). At 4 weeks, her upper limb and lower limb muscle power improved. By 2 months, she was mobilized with support. Her Mini-Mental State Examination showed no cognitive impairment. At the latest follow-up at 1 year, her fractures are completely healed and she has no neurological or functional impairment.
CONCLUSION
We must always suspect isolated cerebral FES as a diagnosis in polytrauma patients even when the classical findings are not present. MRI compatible implants have to be used as far as possible as MRI may be required to confirm the diagnosis of CFE. The early total care with definitive fixation and supportive treatment helped us in this patient's complete recovery without cognitive impairment.
PubMed: 36380992
DOI: 10.13107/jocr.2022.v12.i04.2750