25 results on '"Michelle M. Rank"'
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2. Acid-Sensing Ion Channels: Expression and Function in Resident and Infiltrating Immune Cells in the Central Nervous System
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Victoria S. Foster, Lachlan D. Rash, Glenn F. King, and Michelle M. Rank
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acid-sensing ion channel (ASIC) ,central nervous system ,immune cell ,acidosis ,neuropathology ,neuroimmunology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Peripheral and central immune cells are critical for fighting disease, but they can also play a pivotal role in the onset and/or progression of a variety of neurological conditions that affect the central nervous system (CNS). Tissue acidosis is often present in CNS pathologies such as multiple sclerosis, epileptic seizures, and depression, and local pH is also reduced during periods of ischemia following stroke, traumatic brain injury, and spinal cord injury. These pathological increases in extracellular acidity can activate a class of proton-gated channels known as acid-sensing ion channels (ASICs). ASICs have been primarily studied due to their ubiquitous expression throughout the nervous system, but it is less well recognized that they are also found in various types of immune cells. In this review, we explore what is currently known about the expression of ASICs in both peripheral and CNS-resident immune cells, and how channel activation during pathological tissue acidosis may lead to altered immune cell function that in turn modulates inflammatory pathology in the CNS. We identify gaps in the literature where ASICs and immune cell function has not been characterized, such as neurotrauma. Knowledge of the contribution of ASICs to immune cell function in neuropathology will be critical for determining whether the therapeutic benefits of ASIC inhibition might be due in part to an effect on immune cells.
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- 2021
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- View/download PDF
3. Editorial: Propriospinal Neurons: Essential Elements in Locomotion, Autonomic Function and Plasticity After Spinal Cord Injury and Disease
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Kristine C. Cowley, Michael A. Lane, Claire F. Meehan, Michelle M. Rank, and Katinka Stecina
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propriospinal ,neuron ,respiration ,locomotion ,autonomic function ,motor control ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2021
- Full Text
- View/download PDF
4. Conditional microglial depletion in rats leads to reversible anorexia and weight loss by disrupting gustatory circuitry
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Alita Soch, Simone N. De Luca, Ilvana Ziko, Hao Wang, Michelle M. Rank, Luba Sominsky, and Sarah J. Spencer
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Male ,0301 basic medicine ,medicine.medical_specialty ,media_common.quotation_subject ,Immunology ,Hypothalamus ,Midline Thalamic Nuclei ,Appetite ,Anorexia ,Biology ,Satiety Response ,Eating ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Weight loss ,Internal medicine ,Weight Loss ,medicine ,Animals ,Neuropeptide Y ,Rats, Wistar ,media_common ,Microglia ,Endocrine and Autonomic Systems ,Leptin ,Body Weight ,Brain ,Feeding Behavior ,Ghrelin ,Diet ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,medicine.symptom ,Energy Metabolism ,030217 neurology & neurosurgery - Abstract
Microglia are highly sensitive to dietary influence, becoming activated acutely and long-term by high fat diet. However, their role in regulating satiety and feeding in healthy individuals remains unclear. Here we show that microglia are essential for the normal regulation of satiety and metabolism in rats. Short-term microglial depletion in a Cx3cr1-Dtr rat led to a dramatic weight loss that was largely accounted for by an acute reduction in food intake. This weight loss and anorexia were not likely due to a sickness response since the rats did not display peripheral or central inflammation, withdrawal, anxiety-like behavior, or nausea-associated pica. Hormonal and hypothalamic anatomical changes were largely compensatory to the suppressed food intake, which occurred in association with disruption of the gustatory circuitry at the paraventricular nucleus of the thalamus. Thus, microglia are important in supporting normal feeding behaviors and weight, and regulating preference for palatable food. Inhibiting this circuitry is able to over-ride strong compensatory drives to eat, providing a potential target for satiety control.
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- 2019
5. Evolution of thyroid hormone distributor proteins
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Peter M. Smooker, Thomas McLean, Samantha J. Richardson, and Michelle M. Rank
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Models, Molecular ,0301 basic medicine ,Thyroid Hormones ,endocrine system ,medicine.medical_specialty ,Globulin ,Thyroxine-Binding Globulin ,Gene Expression ,Plasma protein binding ,Biochemistry ,Protein Structure, Secondary ,Evolution, Molecular ,03 medical and health sciences ,Thyroxine-binding globulin ,Endocrinology ,Albumins ,Internal medicine ,medicine ,Animals ,Humans ,Prealbumin ,Selection, Genetic ,Molecular Biology ,Conserved Sequence ,Phylogeny ,030102 biochemistry & molecular biology ,biology ,Thyroid ,Albumin ,nutritional and metabolic diseases ,Protein Transport ,Vitamin D binding ,Transthyretin ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Protein Binding ,Hormone - Abstract
Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins (THDPs) to ensure their efficient distribution through the blood and cerebrospinal fluid in vertebrates. Albumin is a THDP in the blood of all studied species of vertebrates, so may be the original vertebrate THDP. However, albumin has weak affinity for THs. Transthyretin (TTR) has been identified in the blood across different lineages in adults vs juveniles. TTR has intermediate affinity for THs. Thyroxine-binding globulin has only been identified in mammals and has high affinity for THs. Of these THDPs, TTR is the only one known to be synthesised in the brain and is involved in moving THs from the blood into the cerebrospinal fluid. We analysed the rates of evolution of these three THDPs: TTR has been most highly conserved and albumin has had the highest rate of divergence.
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- 2017
6. Effects Of treadmill training on hindlimb muscles of spinal cord-injured mice
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Jamie R. Flynn, Michelle M. Rank, Mary P. Galea, Robin Callister, David L Morgan, Robert J. Callister, and Camila R Battistuzzo
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0301 basic medicine ,Soleus muscle ,Physiology ,business.industry ,education ,Stimulation ,Hindlimb ,Anatomy ,medicine.disease ,Spinal cord ,Muscle atrophy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Atrophy ,Physiology (medical) ,medicine ,Neurology (clinical) ,Treadmill ,medicine.symptom ,business ,Spinal cord injury ,030217 neurology & neurosurgery - Abstract
Treadmill training is known to prevent muscle atrophy after spinal cord injury (SCI), however, the training duration required to optimize recovery has not been investigated. Methods: Hemisected mice were randomized to 3, 6, or 9 weeks of training or no training. Muscle fiber type composition and fiber cross-sectional area (CSA) of medial gastrocnemius (MG), soleus (SOL), and tibialis anterior (TA) were assessed using ATPase histochemistry. Results: Muscle fiber type composition of SCI animals did not change with training. However, 9 weeks of training increased the CSA of IIB and IIX fibers in TA and MG muscles. Conclusions: Nine weeks of training after incomplete SCI was effective in preventing atrophy of fast-twitch muscles but there were limited effects on slow-twitch muscles and muscle fiber type composition. These data provide important evidence of the benefits of exercising paralyzed limbs after SCI.
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- 2016
7. Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection
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Christopher G. Sobey, Henry Ma, Thanh G. Phan, Velandai Srikanth, Brooke J. Wanrooy, Luke Ho, Michelle M. Rank, Michael John de Veer, Tharani Thirugnanachandran, Tara Sepehrizadeh, Shu Wen Wen, Raymond Shim, and Connie H.Y. Wong
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0301 basic medicine ,Male ,medicine.medical_specialty ,Neurology ,Infarction ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine.artery ,Internal medicine ,Severity of illness ,medicine ,Animals ,Humans ,cardiovascular diseases ,Artery occlusion ,Stroke ,Cause of death ,Aged ,business.industry ,General Neuroscience ,Infarction, Middle Cerebral Artery ,Bacterial Infections ,medicine.disease ,Arterial occlusion ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Middle cerebral artery ,Cardiology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.
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- 2019
8. In vivo characterization of colorectal and cutaneous inputs to lumbosacral dorsal horn neurons in the mouse spinal cord
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Robert J. Callister, Brett A. Graham, Michelle M. Rank, Alan M. Brichta, Simon Keely, and Kristen E. Farrell
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Male ,0301 basic medicine ,Patch-Clamp Techniques ,Colon ,Population ,Action Potentials ,Stimulation ,Biophysical Phenomena ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Physical Stimulation ,medicine ,Animals ,Patch clamp ,education ,Posterior Horn Cell ,Skin ,Afferent Pathways ,education.field_of_study ,business.industry ,General Neuroscience ,Lumbosacral Region ,Excitatory Postsynaptic Potentials ,Spinal cord ,Electric Stimulation ,eye diseases ,Mice, Inbred C57BL ,Posterior Horn Cells ,030104 developmental biology ,Rheobase ,medicine.anatomical_structure ,Spinal Cord ,nervous system ,Excitatory postsynaptic potential ,business ,Neuroscience ,030217 neurology & neurosurgery ,Lumbosacral joint - Abstract
Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pain are unknown, clinical and preclinical evidence suggests lumbosacral spinal cord dorsal horn neurons contribute to these symptoms. At present, we know little about the intrinsic and synaptic properties of this population of neurons in either normal or inflammed conditions. Therefore, we developed an in vivo preparation to make patch-clamp recordings from superficial dorsal horn (SDH) neurons receiving colonic inputs in naive male mice. Recordings were made in the lumbosacral spinal cord (L6-S1) under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to determine whether SDH neurons received inputs from mechanical stimulation/distension of the colon. Responses to hind paw/tail cutaneous stimulation and intrinsic and synaptic properties were also assessed, as well as action potential discharge properties. Approximately 11% of lumbosacral SDH neurons in the cohort of neurons sampled responded to CRD and a majority of these responses were subthreshold. Most CRD-responsive neurons (80%) also responded to cutaneous stimuli, compared with
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- 2016
9. Electrophysiological characterization of spontaneous recovery in deep dorsal horn interneurons after incomplete spinal cord injury
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Mary P. Galea, Michelle M. Rank, Jamie R. Flynn, Robin Callister, and Robert J. Callister
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Male ,Patch-Clamp Techniques ,Time Factors ,Spontaneous recovery ,Biophysics ,Action Potentials ,In Vitro Techniques ,Biophysical Phenomena ,Functional Laterality ,Statistics, Nonparametric ,Mice ,chemistry.chemical_compound ,Developmental Neuroscience ,medicine ,Animals ,Patch clamp ,Posterior Horn Cell ,Spinal cord injury ,Spinal Cord Injuries ,Chemistry ,Recovery of Function ,Anatomy ,medicine.disease ,Spinal cord ,Electric Stimulation ,Mice, Inbred C57BL ,Posterior Horn Cells ,Disease Models, Animal ,Electrophysiology ,medicine.anatomical_structure ,Neurology ,CNQX ,Excitatory postsynaptic potential ,Neuroscience - Abstract
In the weeks and months following an incomplete spinal cord injury (SCI) significant spontaneous recovery of function occurs in the absence of any applied therapeutic intervention. The anatomical correlates of this spontaneous plasticity are well characterized, however, the functional changes that occur in spinal cord interneurons after injury are poorly understood. Here we use a T10 hemisection model of SCI in adult mice (9-10 wks old) combined with whole-cell patch clamp electrophysiology and a horizontal spinal cord slice preparation to examine changes in intrinsic membrane and synaptic properties of deep dorsal horn (DDH) interneurons. We made these measurements during short-term (4 wks) and long-term (10 wks) spontaneous recovery after SCI. Several important intrinsic membrane properties are altered in the short-term, but recover to values resembling those of uninjured controls in the longer term. AP discharge patterns are reorganized at both short-term and long-term recovery time points. This is matched by reorganization in the expression of voltage-activated potassium and calcium subthreshold-currents that shape AP discharge. Excitatory synaptic inputs onto DDH interneurons are significantly restructured in long-term SCI mice. Plots of sEPSC peak amplitude vs. rise times suggest considerable dendritic expansion or synaptic reorganization occurs especially during long-term recovery from SCI. Connectivity between descending dorsal column pathways and DDH interneurons is reduced in the short-term, but amplified in long-term recovery. Our results suggest considerable plasticity in both intrinsic and synaptic mechanisms occurs spontaneously in DDH interneurons following SCI and takes a minimum of 10 wks after the initial injury to stabilize.
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- 2015
10. Functional changes in deep dorsal horn interneurons following spinal cord injury are enhanced with different durations of exercise training
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Jamie R. Flynn, Camila R Battistuzzo, Robert J. Callister, Michelle M. Rank, Robin Callister, and Mary P. Galea
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Dorsum ,Physiology ,Postsynaptic Current ,Anatomy ,Spinal cord ,medicine.disease ,Lesion ,medicine.anatomical_structure ,Spinal Cord Dorsal Horn ,Synaptic plasticity ,Excitatory postsynaptic potential ,medicine ,medicine.symptom ,Psychology ,Neuroscience ,Spinal cord injury - Abstract
Following incomplete spinal cord injury (SCI), collaterals sprout from intact and injured axons in the vicinity of the lesion. These sprouts are thought to form new synaptic contacts that effectively bypass the lesion epicentre and contribute to improved functional recovery. Such anatomical changes are known to be enhanced by exercise training; however, the mechanisms underlying exercise-mediated plasticity are poorly understood. Specifically, we do not know how SCI alone or SCI combined with exercise alters the intrinsic and synaptic properties of interneurons in the vicinity of a SCI. Here we use a hemisection model of incomplete SCI in adult mice and whole-cell patch-clamp recording in a horizontal spinal cord slice preparation to examine the functional properties of deep dorsal horn (DDH) interneurons located in the vicinity of a SCI following 3 or 6 weeks of treadmill exercise training. We examined the functional properties of local and descending excitatory synaptic connections by recording spontaneous excitatory postsynaptic currents (sEPSCs) and responses to dorsal column stimulation, respectively. We find that SCI in untrained animals exerts powerful effects on intrinsic, and especially, synaptic properties of DDH interneurons. Plasticity in intrinsic properties was most prominent at 3 weeks post SCI, whereas synaptic plasticity was greatest at 6 weeks post injury. Exercise training did not markedly affect intrinsic membrane properties; however, local and descending excitatory synaptic drive were enhanced by 3 and 6 weeks of training. These results suggest exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.
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- 2014
11. Is more always better? How different 'doses' of exercise after incomplete spinal cord injury affects the membrane properties of deep dorsal horn interneurons
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Michelle M. Rank, Robin Callister, Mary P. Galea, and Robert J. Callister
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0301 basic medicine ,Dorsum ,Male ,Spinal Cord Dorsal Horn ,Time Factors ,Interneuron ,Action Potentials ,Treadmill exercise ,Somatosensory system ,Thoracic Vertebrae ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Developmental Neuroscience ,Interneurons ,Physical Conditioning, Animal ,Medicine ,Animals ,Spinal cord injury ,Spinal Cord Injuries ,business.industry ,Recovery of Function ,Spinal cord ,medicine.disease ,Mice, Inbred C57BL ,Electrophysiology ,030104 developmental biology ,medicine.anatomical_structure ,Rheobase ,nervous system ,Neurology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Interneurons in the deep dorsal horn (DDH) of the spinal cord process somatosensory input, and form an important link between upper and lower motoneurons to subsequently shape motor output. Exercise training after SCI is known to improve functional motor recovery, but little is known about the mechanisms within spinal cord neurons that underlie these improvements. Here we investigate how the properties of DDH interneurons are affected by spinal cord injury (SCI) alone, and SCI in combination with different 'doses' of treadmill exercise training (3, 6, and 9wks). In an adult mouse hemisection model of SCI we used whole-cell patch-clamp electrophysiology to record intrinsic, AP firing and gain modulation properties from DDH interneurons in a horizontal spinal cord slice preparation. We find that neurons within two segments of the injury, both ipsi- and contralateral to the hemisection, are similarly affected by SCI and SCI plus exercise. The passive intrinsic membrane properties input resistance (Rin) and rheobase are sensitive to the effects of recovery time and exercise training after SCI thus altering DDH interneuron excitability. Conversely, select active membrane properties are largely unaffected by either SCI or exercise training. SCI itself causes a mismatch in the expression of voltage-gated subthreshold currents and AP discharge firing type. Over time after SCI, and especially with exercise training (9wks), this mismatched expression is exacerbated. Lastly, amplification properties (i.e. gain of frequency-current relationship) of DDH interneurons are altered by SCI alone and recover spontaneously with no clear effect of exercise training. These results suggest a larger 'dose' of exercise training (9wks) has a strong and selective effect on specific membrane properties, and on the output of interneurons in the vicinity of a SCI. These electrophysiological data provide new insights into the plasticity of DDH interneurons and the mechanisms by which exercise therapy after SCI can improve recovery.
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- 2017
12. Exercise Training after Spinal Cord Injury Selectively Alters Synaptic Properties in Neurons in Adult Mouse Spinal Cord
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Mary P. Galea, Robin Callister, Lynda R. Dunn, Michelle M. Rank, Robert J. Callister, and Jamie R. Flynn
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Male ,Short Communications ,Membrane Potentials ,Mice ,Physical Conditioning, Animal ,medicine ,Animals ,Patch clamp ,Axon ,Spinal cord injury ,Spinal Cord Injuries ,Neurons ,business.industry ,Excitatory Postsynaptic Potentials ,medicine.disease ,Spinal cord ,Electrophysiology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Rheobase ,Spinal Cord ,Anesthesia ,Synapses ,Corticospinal tract ,Excitatory postsynaptic potential ,Neurology (clinical) ,business ,Neuroscience - Abstract
Following spinal cord injury (SCI), anatomical changes such as axonal sprouting occur within weeks in the vicinity of the injury. Exercise training enhances axon sprouting; however, the exact mechanisms that mediate exercised-induced plasticity are unknown. We studied the effects of exercise training after SCI on the intrinsic and synaptic properties of spinal neurons in the immediate vicinity (
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- 2013
13. Gait recovery following spinal cord injury in mice: Limited effect of treadmill training
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Michelle M. Rank, Mary P. Galea, David L Morgan, Robert J. Callister, Camila R Battistuzzo, Robin Callister, and Jamie R. Flynn
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0301 basic medicine ,Male ,medicine.medical_specialty ,Treadmill training ,Running ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Physical medicine and rehabilitation ,Left hindlimb ,Physical Conditioning, Animal ,medicine ,Animals ,Treadmill ,Spinal cord injury ,Gait ,Spinal Cord Injuries ,Research Articles ,business.industry ,Recovery of Function ,medicine.disease ,Spinal cord ,Mice, Inbred C57BL ,Regimen ,030104 developmental biology ,medicine.anatomical_structure ,Gait analysis ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Several studies in rodents with complete spinal cord transections have demonstrated that treadmill training improves stepping movements. However, results from studies in incomplete spinal cord injured animals have been conflicting and questions regarding the training dosage after injury remain unresolved.To assess the effects of treadmill-training regimen (20 minutes daily, 5 days a week) for 3, 6 or 9 weeks on the recovery of locomotion in hemisected SCI mice.A randomized and blinded controlled experimental trial used a mouse model of incomplete spinal cord injury (SCI). After a left hemisection at T10, adult male mice were randomized to trained or untrained groups. The trained group commenced treadmill training one week after surgery and continued for 3, 6 or 9 weeks. Quantitative kinematic gait analysis was used to assess the spatiotemporal characteristics of the left hindlimb prior to injury and at 1, 4, 7 and 10 weeks post-injury.One week after injury there was no movement of the left hindlimb and some animals dragged their foot. Treadmill training led to significant improvements in step duration, but had limited effect on the hindlimb movement pattern. Locomotor improvements in trained animals were most evident at the hip and knee joints whereas recovery of ankle movement was limited, even after 9 weeks of treadmill training.These results demonstrate that treadmill training may lead to only modest improvement in recovery of hindlimb movement after incomplete spinal cord injury in mice.
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- 2016
14. Adrenergic Receptors Modulate Motoneuron Excitability, Sensory Synaptic Transmission and Muscle Spasms After Chronic Spinal Cord Injury
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Katherine C. Murray, Marilee J. Stephens, David J. Bennett, Michelle M. Rank, Monica A. Gorassini, and Jessica M. D'Amico
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Adrenergic Antagonists ,Spasm ,Sensory Receptor Cells ,Adrenergic receptor ,Physiology ,Sensory system ,Neurotransmission ,Synaptic Transmission ,Clonidine ,Rats, Sprague-Dawley ,Norepinephrine ,Idazoxan ,medicine ,Animals ,Spinal cord injury ,Spinal Cord Injuries ,Motor Neurons ,business.industry ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Excitatory Postsynaptic Potentials ,Articles ,Prazosin ,medicine.disease ,Spinal cord ,Adrenergic Agonists ,Alpha-1A adrenergic receptor ,Rats ,Receptors, Adrenergic ,medicine.anatomical_structure ,nervous system ,Chromones ,Models, Animal ,Female ,business ,Neuroscience ,medicine.drug - Abstract
The brain stem provides most of the noradrenaline (NA) present in the spinal cord, which functions to both increase spinal motoneuron excitability and inhibit sensory afferent transmission to motoneurons (excitatory postsynaptic potentials; EPSPs). NA increases motoneuron excitability by facilitating calcium-mediated persistent inward currents (Ca PICs) that are crucial for sustained motoneuron firing. Spinal cord transection eliminates most NA and accordingly causes an immediate loss of PICs and emergence of exaggerated EPSPs. However, with time PICs recover, and thus the exaggerated EPSPs can then readily trigger these PICs, which in turn produce muscle spasms. Here we examined the contribution of adrenergic receptors to spasms in chronic spinal rats. Selective activation of the α1Aadrenergic receptor with the agonists methoxamine or A61603 facilitated Ca PIC and spasm activity, recorded both in vivo and in vitro. In contrast, the α2receptor agonists clonidine and UK14303 did not facilitate Ca PICs, but did decrease the EPSPs that trigger spasms. Moreover, in the absence of agonists, spasms recorded in vivo were inhibited by the α1receptor antagonists WB4010, prazosin, and REC15/2739, and increased by the α2receptor antagonist RX821001, suggesting that both adrenergic receptors were endogenously active. In contrast, spasm activity recorded in the isolated in vitro cord was inhibited only by the α1antagonists that block constitutive receptor activity (activity in the absence of NA; inverse agonists, WB4010 and prazosin) and not by the neutral antagonist REC15/2739, which only blocks conventional NA-mediated receptor activity. RX821001 had no effect in vitro even though it is an α2receptor inverse agonist. Our results suggest that after chronic spinal cord injury Ca PICs and spasms are facilitated, in part, by constitutive activity in α1adrenergic receptors. Additionally, peripherally derived NA (or similar ligand) activates both α1and α2adrenergic receptors, controlling PICs and EPSPs, respectively.
- Published
- 2011
15. Locomotion After Spinal Cord Injury Depends on Constitutive Activity in Serotonin Receptors
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Karim Fouad, Michelle M. Rank, Katherine C. Murray, David J. Bennett, Romana Vavrek, and Leo Sanelli
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Tail ,Serotonin ,Indoles ,Pyridines ,Physiology ,medicine.medical_treatment ,Aminopyridines ,Hindlimb ,Rats, Sprague-Dawley ,Cordotomy ,Plateau potentials ,Serotonin 5-HT2 Receptor Antagonists ,Animals ,Medicine ,Receptor ,Spinal cord injury ,Gait Disorders, Neurologic ,Injections, Spinal ,Spinal Cord Injuries ,5-HT receptor ,Electromyography ,business.industry ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Recovery of Function ,Articles ,medicine.disease ,Rats ,Serotonin Receptor Agonists ,Muscle Hypotonia ,Female ,Receptors, Serotonin, 5-HT2 ,business ,Neuroscience ,Locomotion - Abstract
Following spinal cord injury (SCI) neurons caudal to the injury are capable of rhythmic locomotor-related activity that can form the basis for substantial functional recovery of stepping despite the loss of crucial brain stem-derived neuromodulators like serotonin (5-HT). Here we investigated the contribution of constitutive 5-HT2 receptor activity (activity in the absence of 5-HT) to locomotion after SCI. We used a staggered hemisection injury model in rats to study this because these rats showed a robust recovery of locomotor function and yet a loss of most descending axons. Immunolabeling for 5-HT showed little remaining 5-HT below the injury, and locomotor ability was not correlated with the amount of residual 5-HT. Furthermore, blocking 5-HT2 receptors with an intrathecal (IT) application of the neutral antagonist SB242084 did not affect locomotion (locomotor score and kinematics were unaffected), further indicating that residual 5-HT below the injury did not contribute to generation of locomotion. As a positive control, we found that the same application of SB242084 completely antagonized the muscle activity induced by exogenous application of the 5-HT2 receptor agonists alpha-methyl-5-HT (IT). In contrast, blocking constitutive 5-HT2 receptor activity with the potent inverse agonist SB206553 (IT) severely impaired stepping as assessed with kinematic recordings, eliminating most hindlimb weight support and overall reducing the locomotor score in both hind legs. However, even in the most severely impaired animals, rhythmic sweeping movements of the hindlimb feet were still visible during forelimb locomotion, suggesting that SB206553 did not completely eliminate locomotor drive to the motoneurons or motoneuron excitability. The same application of SB206553 had no affect on stepping in normal rats. Thus while normal rats can compensate for loss of 5-HT2 receptor activity, after severe spinal cord injury rats require constitutive activity in these 5-HT2 receptors to produce locomotion.
- Published
- 2010
16. Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors
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Marilee J. Stephens, Karim Fouad, Monica A. Gorassini, Charles J. Heckman, Aya Nakae, R. Luke Harris, Leo Sanelli, Romana Vavrek, Michelle M. Rank, Takashi Mashimo, Katherine C. Murray, Edward W Ballou, X. Li, Roberta Anelli, David J. Bennett, P. J. Harvey, and Jessica M. D'Amico
- Subjects
Serotonin ,Spasm ,Biology ,Serotonergic ,Article ,General Biochemistry, Genetics and Molecular Biology ,Membrane Potentials ,Rats, Sprague-Dawley ,Plateau potentials ,Postsynaptic potential ,Receptor, Serotonin, 5-HT2C ,medicine ,Animals ,Humans ,Protein Isoforms ,Spasticity ,Receptor ,Spinal cord injury ,Spinal Cord Injuries ,5-HT receptor ,Motor Neurons ,General Medicine ,medicine.disease ,Rats ,Up-Regulation ,Anesthesia ,Calcium ,Female ,medicine.symptom ,Receptors, Serotonin, 5-HT2 ,Neuroscience ,Locomotion - Abstract
Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy.
- Published
- 2010
17. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors
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Marilee J. Stephens, Michelle M. Rank, David J. Bennett, Jessica M. D'Amico, Monica A. Gorassini, and Katherine C. Murray
- Subjects
Sacrum ,Spasm ,Physiology ,Neural Inhibition ,medicine ,Animals ,Spasticity ,Receptor ,Spinal cord injury ,Spinal Cord Injuries ,business.industry ,General Neuroscience ,Excitatory Postsynaptic Potentials ,Articles ,Serotonin 5-HT1 Receptor Agonists ,medicine.disease ,Electric Stimulation ,Rats ,Sensory afferents ,Receptors, Serotonin ,Excitatory postsynaptic potential ,Reflex ,Receptor, Serotonin, 5-HT1B ,Female ,Serotonin ,medicine.symptom ,business ,Neuroscience - Abstract
Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT1B or 5-HT1F receptor agonists, including zolmitriptan (5-HT1B/1D/1F) and LY344864 (5-HT1F), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC50) and potency (−log EC50). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT1B and 5-HT1F receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT1B receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT1B agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT1B receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at −73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT1B/1F agonists, such as zolmitriptan, can restore inhibition of sensory transmission after SCI without affecting general motoneuron function and thus may serve as a novel class of antispastic drugs.
- Published
- 2011
18. Role of endogenous release of norepinephrine in muscle spasms after chronic spinal cord injury
- Author
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Monica A. Gorassini, Michelle M. Rank, X. Li, and David J. Bennett
- Subjects
medicine.medical_specialty ,Spasm ,Patch-Clamp Techniques ,Physiology ,Withdrawal reflex ,Tetrodotoxin ,In Vitro Techniques ,Article ,Membrane Potentials ,Rats, Sprague-Dawley ,Norepinephrine ,Plateau potentials ,Anterior Horn Cells ,Internal medicine ,Medicine ,Animals ,Anesthetics, Local ,Amphetamine ,Spinal cord injury ,Spinal Cord Injuries ,Skin ,Adrenergic Uptake Inhibitors ,Dose-Response Relationship, Drug ,business.industry ,Electromyography ,General Neuroscience ,medicine.disease ,Electric Stimulation ,Rats ,Disease Models, Animal ,Endocrinology ,Chronic Disease ,Reflex ,Female ,Serotonin ,medicine.symptom ,business ,Neuroscience ,Muscle contraction ,medicine.drug ,Muscle Contraction - Abstract
The recovery of persistent inward currents (PICs) and motoneuron excitability after chronic spinal cord transection is mediated, in part, by the development of supersensitivity to residual serotonin (5HT) below the lesion. The purpose of this paper is to investigate if, like 5HT, endogenous sources of norepinephrine (NE) facilitate motoneuron PICs after chronic spinal transection. Cutaneous-evoked reflex responses in tail muscles of awake chronic spinal rats were measured after increasing presynaptic release of NE by administration of amphetamine. An increase in long-lasting reflexes, known to be mediated by the calcium component of the PIC (CaPIC), was observed even at low doses (0.1–0.2 mg/kg) of amphetamine. These findings were repeated in a reduced S2 in vitro preparation, demonstrating that the increased long-lasting reflexes by amphetamine were neural. Under intracellular voltage clamp, amphetamine application led to a large facilitation of the motoneuron CaPIC. This indicates that the increases in long-lasting reflexes induced by amphetamine in the awake animal were, in part, due to actions directly on the motoneuron. Reflex responses in acutely spinal animals were facilitated by amphetamine similar to chronic animals but only at doses that were ten times greater than that required in chronic animals (0.2 mg/kg chronic vs. 2.0 mg/kg acute), pointing to a development of supersensitivity to endogenous NE in chronic animals. In summary, the increases in long-lasting reflexes and associated motoneuron CaPICs by amphetamine are likely due to an increased release of endogenous NE, which motoneurons become supersensitive to in the chronic stages of spinal cord injury.
- Published
- 2007
19. Role of endogenous release of norepinephrine in muscle spasms after chronic spinal cord injury.
- Author
-
Michelle M Rank, Xiaole Li, David J Bennett, and Monica A Gorassini
- Subjects
- *
NORADRENALINE , *MUSCLE cramps , *SPINAL cord injuries , *MOTOR neurons , *LABORATORY rats , *AMPHETAMINES , *SEROTONIN - Abstract
The recovery of persistent inward currents (PICs) and motoneuron excitability after chronic spinal cord transection is mediated, in part, by the development of supersensitivity to residual serotonin (5HT) below the lesion. The purpose of this paper is to investigate if, like 5HT, endogenous sources of norepinephrine (NE) facilitate motoneuron PICs after chronic spinal transection. Cutaneous-evoked reflex responses in tail muscles of awake chronic spinal rats were measured after increasing presynaptic release of NE by administration of amphetamine. An increase in long-lasting reflexes, known to be mediated by the calcium component of the PIC (CaPIC), was observed even at low doses (0.1-0.2 mg/kg) of amphetamine. These findings were repeated in a reduced S2 in vitro preparation, demonstrating that the increased long-lasting reflexes by amphetamine were neural. Under intracellular voltage clamp, amphetamine application led to a large facilitation of the motoneuron CaPIC. This indicates that the increases in long-lasting reflexes induced by amphetamine in the awake animal were, in part, due to actions directly on the motoneuron. Reflex responses in acutely spinal animals were facilitated by amphetamine similar to chronic animals but only at doses that were ten times greater than that required in chronic animals (0.2 mg/kg chronic vs. 2.0 mg/kg acute), pointing to a development of supersensitivity to endogenous NE in chronic animals. In summary, the increases in long-lasting reflexes and associated motoneuron CaPICs by amphetamine are likely due to an increased release of endogenous NE, which motoneurons become supersensitive to in the chronic stages of spinal cord injury. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
20. Assessments Used for Summative Purposes during Internal Medicine Specialist Training: A Rapid Review
- Author
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Scott Patterson, Louise Shaw, Michelle M Rank, and Brett Vaughan
- Subjects
rapid review ,summative assessment ,clinical competency ,medical training ,Education - Abstract
Assessments used for summative purposes of patient-facing clinical competency in specialist internal medicine training are high-stakes, both to doctors in training, as it is a prerequisite for qualification, as well as their community of prospective patients. A rapid review of the literature evaluated methods of assessments used for summative purposes of patient-facing clinical competency during specialist internal medicine training in Australia. Four online databases identified literature published since the year 2000 that reported on summative assessment in specialist medical training. Two reviewers screened and selected eligible studies and extracted data, with a focus on evidence of support for the criteria for good assessment as set out in the 2010 Ottawa Consensus framework for good assessment. Ten eligible studies were included. Four studied the mini-clinical evaluation exercise (mini-CEX), two the Royal Australasian College of Physicians short case exam, three a variety of Entrustable Professional Activities (EPAs) or summative entrustment and progression review processes, and one a novel clinical observation tool. The mini-CEX assessment demonstrated the most evidence in support of the Ottawa criteria. There was a paucity of published evidence regarding the best form of summative assessment of patient-facing clinical competency in specialist internal medicine training.
- Published
- 2023
- Full Text
- View/download PDF
21. Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection.
- Author
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Shim R, Wen SW, Wanrooy BJ, Rank M, Thirugnanachandran T, Ho L, Sepehrizadeh T, de Veer M, Srikanth VK, Ma H, Phan TG, Sobey CG, and Wong CHY
- Subjects
- Aged, Animals, Disease Models, Animal, Female, Humans, Infarction, Middle Cerebral Artery, Male, Mice, Inbred C57BL, Risk Factors, Severity of Illness Index, Bacterial Infections complications, Stroke microbiology, Stroke pathology
- Abstract
Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.
- Published
- 2020
- Full Text
- View/download PDF
22. SISCOM in children with tuberous sclerosis complex-related epilepsy.
- Author
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Aboian MS, Wong-Kisiel LC, Rank M, Wetjen NM, Wirrell EC, and Witte RJ
- Subjects
- Adolescent, Child, Child, Preschool, Epilepsy complications, Epilepsy surgery, Follow-Up Studies, Humans, Infant, Magnetic Resonance Imaging methods, Tuberous Sclerosis complications, Tuberous Sclerosis surgery, Epilepsy diagnostic imaging, Tomography, Emission-Computed, Single-Photon methods, Tuberous Sclerosis diagnostic imaging
- Abstract
Identification of a single epileptogenic focus in patients with tuberous sclerosis complex is a challenge. Noninvasive imaging modalities, including subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging (SISCOM), have been used to determine the dominant epileptogenic focus for surgical resection. We assessed whether complete resection of SISCOM hyperperfusion abnormality correlates with seizure-free outcome in 6 children with tuberous sclerosis complex-related epilepsy. The median seizure onset age was 4 months (range 1 day to 16 months). The age at surgery ranged from 8 months to 13 years. A dominant SISCOM hyperperfusion focus was identified in 5 patients with multiple tubers. SISCOM provided additional localizing information for epilepsy surgery in 3 patients with nonlocalizing or discordant electrophysiologic and neuroimaging findings. At a minimum of 2 years' follow-up, 3 patients were free of seizures overall. Freedom from seizures was associated with complete resection of SISCOM abnormality in 2 patients. These findings demonstrate that SISCOM can be useful in identifying the epileptogenic zone and in guiding the location and extent of epilepsy surgery in children with tuberous sclerosis complex and multifocal abnormalities. In children with tuberous sclerosis complex and intractable epilepsy, complete resection of the SISCOM hyperperfusion abnormality is associated with freedom from seizures., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
23. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors.
- Author
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Murray KC, Stephens MJ, Rank M, D'Amico J, Gorassini MA, and Bennett DJ
- Subjects
- Animals, Electric Stimulation methods, Excitatory Postsynaptic Potentials drug effects, Female, Rats, Sacrum, Serotonin 5-HT1 Receptor Agonists pharmacology, Serotonin 5-HT1 Receptor Agonists therapeutic use, Spasm prevention & control, Receptor, Serotonin, 5-HT1F, Excitatory Postsynaptic Potentials physiology, Neural Inhibition physiology, Receptor, Serotonin, 5-HT1B physiology, Receptors, Serotonin physiology, Spasm physiopathology, Spinal Cord Injuries physiopathology
- Abstract
Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT(1B) or 5-HT(1F) receptor agonists, including zolmitriptan (5-HT(1B/1D/1F)) and LY344864 (5-HT(1F)), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC(50)) and potency (-log EC(50)). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT(1B) and 5-HT(1F) receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT(1B) receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT(1B) agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT(1B) receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at -73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT(1B/1F) agonists, such as zolmitriptan, can restore inhibition of sensory transmission after SCI without affecting general motoneuron function and thus may serve as a novel class of antispastic drugs.
- Published
- 2011
- Full Text
- View/download PDF
24. Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors.
- Author
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Murray KC, Nakae A, Stephens MJ, Rank M, D'Amico J, Harvey PJ, Li X, Harris RL, Ballou EW, Anelli R, Heckman CJ, Mashimo T, Vavrek R, Sanelli L, Gorassini MA, Bennett DJ, and Fouad K
- Subjects
- Animals, Calcium physiology, Female, Humans, Membrane Potentials physiology, Protein Isoforms physiology, Rats, Rats, Sprague-Dawley, Receptors, Serotonin, 5-HT2 physiology, Serotonin physiology, Spasm physiopathology, Up-Regulation physiology, Locomotion physiology, Motor Neurons physiology, Receptor, Serotonin, 5-HT2C physiology, Spinal Cord Injuries physiopathology
- Abstract
Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy.
- Published
- 2010
- Full Text
- View/download PDF
25. Spastic tail muscles recover from myofiber atrophy and myosin heavy chain transformations in chronic spinal rats.
- Author
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Harris RL, Putman CT, Rank M, Sanelli L, and Bennett DJ
- Subjects
- Aging physiology, Animals, Atrophy, Electromyography, Electrophoresis, Polyacrylamide Gel, Female, Immunohistochemistry, Motor Neurons physiology, Muscle, Skeletal innervation, Physical Exertion physiology, Rats, Rats, Sprague-Dawley, Tail innervation, Tail physiology, Muscle Fibers, Skeletal pathology, Muscle Spasticity metabolism, Muscle Spasticity pathology, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Myosin Heavy Chains metabolism, Spinal Cord Injuries metabolism, Spinal Cord Injuries pathology
- Abstract
Without intervention after spinal cord injury (SCI), paralyzed skeletal muscles undergo myofiber atrophy and slow-to-fast myofiber type transformations. We hypothesized that chronic spasticity-associated neuromuscular activity after SCI would promote recovery from such deleterious changes. We examined segmental tail muscles of chronic spinal rats with long-standing tail spasticity (7 mo after sacral spinal cord transection; older chronic spinals), chronic spinal rats that experienced less spasticity early after injury (young chronic spinals), and rats without spasticity after transection and bilateral deafferentation (spinal isolated). These were compared with tail muscles of age-matched normal rats. Using immunohistochemistry, we observed myofiber distributions of 15.9 +/- 3.5% type I, 18.7 +/- 10.7% type IIA, 60.8 +/- 12.6% type IID(X), and 2.3 +/- 1.3% type IIB (means +/- SD) in young normals, which were not different in older normals. Young chronic spinals demonstrated transformations toward faster myofiber types with decreased type I and increased type IID(X) paralleled by atrophy of all myofiber types compared with young normals. Spinal isolated rats also demonstrated decreased type I myofiber proportions and increased type II myofiber proportions, and severe myofiber atrophy. After 4 mo of complete spasticity (older chronic spinals), myofiber type transformations were reversed, with no significant differences in type I, IIA, IID(X), or IIB proportions compared with age-matched normals. Moreover, after this prolonged spasticity, type I, IIA, and IIB myofibers recovered from atrophy, and type IID(X) myofibers partially recovered. Our results indicate that early after transection or after long-term spinal isolation, relatively inactive tail myofibers atrophy and transform toward faster myofiber types. However, long-term spasticity apparently produces neuromuscular activity that promotes recovery of myofiber types and myofiber sizes.
- Published
- 2007
- Full Text
- View/download PDF
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