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Neurology International Sep 2019A 69-year-old man who had been bedridden in nursing home because of a 5- year history of progressive supranuclear palsy (PSP) was admitted due to aspiration pneumonia....
A 69-year-old man who had been bedridden in nursing home because of a 5- year history of progressive supranuclear palsy (PSP) was admitted due to aspiration pneumonia. Besides neck dystonia in extension, he showed "alternating flexed-extended posturing", in which the arm was flexed on one side and extended on the other. Magnetic resonance imaging of the brain revealed global cerebral atrophy that predominantly affected the cortex and midbrain. The mechanisms of complex posturing in late-stage PSP may sometimes be related to decortication and decerebration as well as dystonia, and "alternating flexed- extended posturing" might be one of the phenotypes of pathological progression in PSP.
PubMed: 31579148
DOI: 10.4081/ni.2019.8257 -
Neurocritical Care Apr 2020
Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic beta-Antagonists; Autonomic Nervous System Diseases; Brain Injuries, Traumatic; Decerebrate State; Dopamine Agonists; GABA-A Receptor Agonists; GABA-B Receptor Agonists; History, 20th Century; History, 21st Century; Humans; Hypertension; Hyperthermia; Neurology; Neurosurgery; Receptors, Dopamine D2; Tachycardia; Tachypnea
PubMed: 31981019
DOI: 10.1007/s12028-020-00917-3 -
The Journal of Physiology Aug 2020The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR). The decerebrate mouse model of the EPR is similar to the previously described...
KEY POINTS
The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR). The decerebrate mouse model of the EPR is similar to the previously described decerebrate rat model. Studying the EPR in transgenic mouse models can define exact mechanisms of the EPR in health and disease.
ABSTRACT
The exercise pressor reflex (EPR) is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to exercise and is necessary to match metabolic demand and prevent premature fatigue. While this reflex is readily tested in humans, mechanistic studies are largely infeasible. Here, we have developed a novel murine model of the EPR to allow for mechanistic studies in various mouse models. We observed that ventral root stimulation (VRS) in an anaesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR which is abolished by dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate a reduced MAP response to VRS using TRPV1 antagonism or in Trpv1 null mice while the response to passive stretch remains intact. Additionally, we demonstrate that intra-arterial infusion of capsaicin results in a dose-related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist or is completely abolished in Trpv1 null mice. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, and for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.
Topics: Animals; Blood Pressure; Decerebrate State; Disease Models, Animal; Heart Rate; Mice; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 32406099
DOI: 10.1113/JP277602 -
Journal of Neurophysiology Apr 2021We recently demonstrated in decerebrate and conscious cat preparations that hindlimb somatosensory inputs converge with vestibular afferent input onto neurons in...
We recently demonstrated in decerebrate and conscious cat preparations that hindlimb somatosensory inputs converge with vestibular afferent input onto neurons in multiple central nervous system (CNS) locations that participate in balance control. Although it is known that head position and limb state modulate postural reflexes, presumably through vestibulospinal and reticulospinal pathways, the combined influence of the two inputs on the activity of neurons in these brainstem regions is unknown. In the present study, we evaluated the responses of vestibular nucleus (VN) neurons to vestibular and hindlimb stimuli delivered separately and together in conscious cats. We hypothesized that VN neuronal firing during activation of vestibular and limb proprioceptive inputs would be well fit by an additive model. Extracellular single-unit recordings were obtained from VN neurons. Sinusoidal whole body rotation in the roll plane was used as the search stimulus. Units responding to the search stimulus were tested for their responses to 10° ramp-and-hold roll body rotation, 60° extension hindlimb movement, and both movements delivered simultaneously. Composite response histograms were fit by a model of low- and high-pass filtered limb and body position signals using least squares nonlinear regression. We found that VN neuronal activity during combined vestibular and hindlimb proprioceptive stimulation in the conscious cat is well fit by a simple additive model for signals with similar temporal dynamics. The mean value for goodness of fit across all units was 0.74 ± 0.17. It is likely that VN neurons that exhibit these integrative properties participate in adjusting vestibulospinal outflow in response to limb state. Vestibular nucleus neurons receive convergent information from hindlimb somatosensory inputs and vestibular inputs. In this study, extracellular single-unit recordings of vestibular nucleus neurons during conditions of passively applied limb movement, passive whole body rotations, and combined stimulation were well fit by an additive model. The integration of hindlimb somatosensory inputs with vestibular inputs at the first stage of vestibular processing suggests that vestibular nucleus neurons account for limb position in determining vestibulospinal responses to postural perturbations.
Topics: Afferent Pathways; Animals; Behavior, Animal; Cats; Electrophysiological Phenomena; Female; Hindlimb; Movement; Neurons; Physical Stimulation; Postural Balance; Proprioception; Vestibular Nuclei; Vestibule, Labyrinth
PubMed: 33534649
DOI: 10.1152/jn.00350.2019 -
The Journal of Neuroscience : the... Apr 2022Higher vertebrates are capable not only of forward but also backward and sideways locomotion. Also, single steps in different directions are generated for postural...
Higher vertebrates are capable not only of forward but also backward and sideways locomotion. Also, single steps in different directions are generated for postural corrections. While the networks responsible for the control of forward walking (FW) have been studied in considerable detail, the networks controlling steps in other directions are mostly unknown. Here, to characterize the operation of the spinal locomotor network during FW and backward walking (BW), we recorded the activity of individual spinal interneurons from L4 to L6 during both FW and BW evoked by epidural stimulation (ES) of the spinal cord at L5-L6 in decerebrate cats of either sex. Three groups of neurons were revealed. Group 1 (45%) had a similar phase of modulation during both FW and BW. Group 2 (27%) changed the phase of modulation in the locomotor cycle depending on the direction of locomotion. Group 3 neurons were modulated during FW only (Group 3a, 21%) or during BW only (Group 3b, 7%). We suggest that Group 1 neurons belong to the network generating the vertical component of steps (the limb elevation and lowering) because it should operate similarly during locomotion in any direction, while Groups 2 and 3 neurons belong to the networks controlling the direction of stepping. Results of this study provide new insights into the organization of the spinal locomotor circuits, advance our understanding of ES therapeutic effects, and can potentially be used for the development of novel strategies for recuperation of impaired balance control, which requires the generation of corrective steps in different directions. Animals and humans can perform locomotion in different directions in relation to the body axis (forward, backward, sideways). While the networks that control forward walking have been studied in considerable detail, the networks controlling steps in other directions are unknown. Here, by recording the activity of the same spinal neurons during forward and backward walking, we revealed three groups of neurons forming, respectively, the network operating similarly during stepping in different directions, the network changing its operation with a change in the direction of stepping, and the network operating only during locomotion in a specific direction. These networks presumably control different aspects of the step. The obtained results provide new insights into the organization of the spinal locomotor networks.
Topics: Animals; Epidural Space; Interneurons; Locomotion; Spinal Cord; Walking
PubMed: 35296546
DOI: 10.1523/JNEUROSCI.1884-21.2022 -
Paediatric Respiratory Reviews Sep 2020Cystic fibrosis liver disease (CFLD) affects a large proportion of cystic fibrosis (CF) patients; however encephalopathy is a rare complication. While classical hepatic... (Review)
Review
Cystic fibrosis liver disease (CFLD) affects a large proportion of cystic fibrosis (CF) patients; however encephalopathy is a rare complication. While classical hepatic encephalopathy can be a feature of end-stage liver disease, "hyperammonemic encephalopathy" can be precipitated in previously stable CFLD by various triggers including systemic corticosteroids. We describe one such case and review the relevant literature.
Topics: Adolescent; Brain Diseases, Metabolic; Confusion; Consciousness Disorders; Cystic Fibrosis; Decerebrate State; Hepatic Encephalopathy; Humans; Hyperammonemia; Liver Cirrhosis; Male
PubMed: 32800451
DOI: 10.1016/j.prrv.2020.03.003 -
American Journal of Physiology. Heart... Aug 2023Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex, which contributes to...
Stimulation of mechanically sensitive channels on the sensory endings of group III and IV thin fiber muscle afferents activates the mechanoreflex, which contributes to reflex increases in sympathetic nerve activity (SNA) and blood pressure during exercise. Accumulating evidence suggests that activation of the nonselective cation channel transient receptor potential vanilloid-1 (TRPV1) on the sensory endings of thin fiber afferents with capsaicin may attenuate mechanosensation. However, no study has investigated the effect of capsaicin on the mechanoreflex. We tested the hypothesis that in male and female decerebrate, unanesthetized rats, the injection of capsaicin (0.05 µg) into the arterial supply of the hindlimb reduces the pressor and renal SNA (RSNA) response to 30 s of 1 Hz rhythmic hindlimb muscle stretch (a model of isolated mechanoreflex activation). In male rats ( = 8), capsaicin injection significantly reduced the integrated blood pressure (blood pressure index or BPI: pre, 363 ± 78; post, 211 ± 88 mmHg·s; = 0.023) and RSNA [∫ΔRSNA; pre, 687 ± 206; post, 216 ± 80 arbitrary units (au), = 0.049] response to hindlimb muscle stretch. In female rats ( = 8), capsaicin injection had no significant effect on the pressor (BPI; pre: 277 ± 67; post: 207 ± 77 mmHg·s; = 0.343) or RSNA (∫ΔRSNA: pre, 697 ± 123; post, 440 ± 183 au; = 0.307) response to hindlimb muscle stretch. The data suggest that the injection of capsaicin into the hindlimb arterial supply to stimulate TRPV1 on the sensory endings of thin fiber muscle afferents attenuates the mechanoreflex in healthy male, but not female, rats. The findings may carry important implications for chronic conditions in which an exaggerated mechanoreflex contributes to aberrant sympathoexcitation during exercise. Recent evidence in isolated sensory neurons indicates that capsaicin-induced stimulation of TRPV1 attenuates mechanosensitivity. Here we demonstrate for the first time that capsaicin exposure/administration reduces the reflex pressor and renal sympathetic nerve response to mechanoreflex activation in male rats, but not female rats, in vivo. Our data may carry important clinical implications for chronic diseases which have been linked to an exaggerated mechanoreflex, at least in males.
Topics: Rats; Male; Animals; Muscle Contraction; Muscle, Skeletal; Capsaicin; Rats, Sprague-Dawley; Reflex; Blood Pressure; Hindlimb
PubMed: 37389947
DOI: 10.1152/ajpheart.00237.2023 -
The Neurodiagnostic Journal Mar 2020A severe and unusual complication found in children with influenza is an acute necrotizing encephalopathy. A 20-month-old female with no significant past medical history...
A severe and unusual complication found in children with influenza is an acute necrotizing encephalopathy. A 20-month-old female with no significant past medical history was admitted to our facility, presenting with a 4-day history of worsening fever, upper respiratory symptoms, new-onset altered mental status and episodes of extensor posturing. The initial concern was a dystonic reaction secondary to promethazine following a recent diagnosis of influenza A virus. A head computed tomography scan indicated concern for widespread edema, and the video EEG revealed focal slowing in the frontocentral regions with no epileptiform activity during episodes of extensor posturing. The first magnetic resonance imaging results were consistent with acute hemorrhagic encephalitis or severe anoxic brain injury for which there is a broad differential. A second MRI five days later found new areas of restricted diffusion that were consistent with acute necrotizing encephalitis.
Topics: Brain; Decerebrate State; Electroencephalography; Female; Humans; Infant; Influenza A virus; Influenza, Human; Leukoencephalitis, Acute Hemorrhagic; Magnetic Resonance Imaging
PubMed: 32101112
DOI: 10.1080/21646821.2020.1725864 -
Frontiers in Neural Circuits 2020: The spinal cord's central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more...
: The spinal cord's central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS. : The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings. : In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle. : Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.
Topics: Ablation Techniques; Animals; Brain; Cats; Cerebral Cortex; Decerebrate State; Electric Stimulation; Motor Neurons; Peripheral Nerves; Reflex, Monosynaptic; Serotonin; Serotonin Antagonists; Spinal Cord; Superior Colliculi
PubMed: 32174815
DOI: 10.3389/fncir.2020.00001 -
Journal of Vascular Research 2020Palmitoylethanolamide is an endogenous lipid that exerts complex vascular effects, enhances the effects of endocannabinoids and induces a direct hypotension, but the...
Palmitoylethanolamide is an endogenous lipid that exerts complex vascular effects, enhances the effects of endocannabinoids and induces a direct hypotension, but the mechanisms involved have been poorly explored. Hence, this study investigated in Wistar pithed rats the role of CB1, CB2, TRPV1 and GPR55 receptors in the inhibition by palmitoylethanolamide of the vasopressor responses produced by sympathetic stimulation or exogenous noradrenaline. Frequency- and dose-dependent vasopressor responses were analysed before and during intravenous (i.v.) continuous infusions of palmitoylethanolamide in animals receiving i.v. bolus of the antagonists NIDA41020 (CB1), AM630 (CB2), capsazepine (TRPV1), and/or cannabidiol (GPR55). Palmitoyletha-nolamide (0.1-3.1 μg/kg/min) dose-dependently inhibited the sympathetically induced and noradrenaline-induced vasopressor responses. Both inhibitions were: (i) partially blocked by 100 μg/kg NIDA41020, 100 μg/kg capsazepine, or 31 μg/kg cannabidiol; (ii) unaffected by 310 μg/kg AM630; and (iii) abolished by the combination NIDA41020 + capsazepine + cannabidiol (100, 100, and 31 μg/kg, respectively). The resting blood pressure was decreased by palmitoylethanolamide (effect prevented by NIDA41020, capsazepine or cannabidiol, but not by AM630). These results suggest that: (i) palmitoylethanolamide inhibits the vasopressor responses to sympathetic stimulation and exogenous noradrenaline and that it induces hypotension; and (ii) all these effects are mediated by prejunctional and vascular CB1, TRPV1 and probably GPR55, but not by CB2, receptors.
Topics: Amides; Animals; Arteries; Decerebrate State; Electric Stimulation; Ethanolamines; Male; Norepinephrine; Palmitic Acids; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Signal Transduction; Sympathetic Nervous System; Sympathomimetics; TRPV Cation Channels; Vasodilation; Vasodilator Agents
PubMed: 32248195
DOI: 10.1159/000506158