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1.
Pain Pract ; 24(3): 483-488, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38041599

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) is a cost-effective option for treating refractory persistent spinal pain syndrome type-2 (PSPS-2). For patients with extensive spine instrumentation including the thoraco-lumbar junction, percutaneous placement of SCS leads is usually not an option being paddle leads typically implanted anterograde. Paddle lead placement will be particularly challenging in more complex cases when the instrumentation covers the targeted level. To overcome this barrier, we studied using a retrograde approach to reach the sweet spot, facilitate the placement, and reduce associated risks. OBJECTIVES: To study the use of retrograde SCS paddle as a placement method to optimize the spinal cord target and reduce the risks of conventional placement in complex cases. STUDY DESIGN: Case series and technical note. METHODS: We present three cases of thoracic retrograde SCS paddle lead placement cases, detailing patient selection, operative technique, and outcome. All the cases had extensive instrumentation to the thoraco-lumbar spine, and one had additional spinal canal stenosis. The surgical procedure entailed a retrograde midthoracic inter-laminar approach, flavectomy, and caudal placement of the paddle lead with intraoperative neurophysiologic monitoring (IONM) guidance for functional midline determination. RESULTS: All the cases had a successful lead placement over the sweet spot without complications. The same approach was used to decompress a focal spinal stenosis in one case. One case had significantly improved pain and hence underwent a pulse generator implant. The other cases had non-satisfactory pain control and were explanted. LIMITATIONS: These case description could guide technical procedural steps, however, a larger number of such cases would be needed to describe further technical nuances. CONCLUSIONS: We demonstrated that placing SCS paddle leads via retrograde midthoracic approach with IONM guidance is safe. This procedure should be an option for SCS paddle implants in patients with posterior spinal fusion encompassing the intended targeted spinal stimulation level.


Assuntos
Dor Intratável , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Resultado do Tratamento , Coluna Vertebral , Medula Espinal/fisiologia , Eletrodos Implantados
2.
FASEB J ; 38(1): e23380, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38102980

RESUMO

The urinary bladder is supplied by a rich network of sensory and autonomic axons, commonly visualized by immunolabeling for neural markers. This approach demonstrates overall network patterning but is less suited to understanding the structure of individual motor and sensory terminals within these complex plexuses. There is a further limitation visualizing the lightly myelinated (A-delta) class of sensory axons that provides the primary mechanosensory drive for initiation of voiding. Whereas most unmyelinated sensory axons can be revealed by immunolabeling for specific neuropeptides, to date no unique neural marker has been identified to immunohistochemically label myelinated visceral afferents. We aimed to establish a non-surgical method to visualize and map myelinated afferents in the bladder in rats. We found that in rats, the adeno-associated virus (AAV), AAV-PHP.S, which shows a high tropism for the peripheral nervous system, primarily transduced myelinated dorsal root ganglion neurons, enabling us to identify the structure and regional distribution of myelinated (mechanosensory) axon endings within the muscle and lamina propria of the bladder. We further identified the projection of myelinated afferents within the pelvic nerve and lumbosacral spinal cord. A minority of noradrenergic and cholinergic neurons in pelvic ganglia were transduced, enabling visualization and regional mapping of both autonomic and sensory axon endings within the bladder. Our study identified a sparse labeling approach for investigating myelinated sensory and autonomic axon endings within the bladder and provides new insights into the nerve-bladder interface.


Assuntos
Dependovirus , Bexiga Urinária , Ratos , Animais , Dependovirus/genética , Neurônios , Axônios , Medula Espinal/fisiologia , Gânglios Espinais , Neurônios Aferentes
3.
World Neurosurg ; 182: e891-e898, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128757

RESUMO

OBJECTIVE: Spinal cord stimulators (SCSs) can be implanted via a percutaneous or paddle approach, the latter technique requiring a laminotomy or laminectomy. Revision surgery may be necessary in instances of migrated, misplaced, or failed stimulators. When revision of a percutaneous system is necessary, it is common to replace the electrodes with a paddle SCS. This study aims to describe a case series of patients with failed paddle SCS electrodes who underwent revision with percutaneous SCS hardware. METHODS: A series of 5 patients were retrospectively analyzed. Medical records were reviewed for demographic data, operative technique, postoperative follow-up, and complications. RESULTS: Five patients were included in this series. The median age was 63 (range 51-84), and the median duration from initial implantation to revision surgery was 19 months (range 5-60). The median operative duration was 92 minutes (mean 99 ± 19.6 minutes). The median length of follow-up after surgery was 24 months (mean 21.8 ± 6.0 months). All patients had improved pain relief and therapeutic coverage with no complications. CONCLUSIONS: Paddle-to-percutaneous SCS surgery is a feasible and durable revision option in appropriately selected patients.


Assuntos
Estimulação da Medula Espinal , Humanos , Pessoa de Meia-Idade , Estimulação da Medula Espinal/métodos , Estudos Retrospectivos , Medula Espinal/cirurgia , Medula Espinal/fisiologia , Eletrodos Implantados , Manejo da Dor/métodos
4.
J Exp Biol ; 226(15)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37565347

RESUMO

Animal locomotion is the result of complex and multi-layered interactions between the nervous system, the musculo-skeletal system and the environment. Decoding the underlying mechanisms requires an integrative approach. Comparative experimental biology has allowed researchers to study the underlying components and some of their interactions across diverse animals. These studies have shown that locomotor neural circuits are distributed in the spinal cord, the midbrain and higher brain regions in vertebrates. The spinal cord plays a key role in locomotor control because it contains central pattern generators (CPGs) - systems of coupled neuronal oscillators that provide coordinated rhythmic control of muscle activation that can be viewed as feedforward controllers - and multiple reflex loops that provide feedback mechanisms. These circuits are activated and modulated by descending pathways from the brain. The relative contributions of CPGs, feedback loops and descending modulation, and how these vary between species and locomotor conditions, remain poorly understood. Robots and neuromechanical simulations can complement experimental approaches by testing specific hypotheses and performing what-if scenarios. This Review will give an overview of key knowledge gained from comparative vertebrate experiments, and insights obtained from neuromechanical simulations and robotic approaches. We suggest that the roles of CPGs, feedback loops and descending modulation vary among animals depending on body size, intrinsic mechanical stability, time required to reach locomotor maturity and speed effects. We also hypothesize that distal joints rely more on feedback control compared with proximal joints. Finally, we highlight important opportunities to address fundamental biological questions through continued collaboration between experimentalists and engineers.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Animais , Retroalimentação , Locomoção/fisiologia , Medula Espinal/fisiologia , Vertebrados
5.
Brain Res ; 1817: 148484, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37442249

RESUMO

Spinal cord injury (SCI) can cause paralysis with a high disease burden with limited treatment options. A single intravenous infusion of mesenchymal stem cells (MSCs) improves motor function in rat SCI models, possibly through the induction of axonal sprouting and remyelination. Repeated infusions (thrice at weekly intervals) of MSCs were administered to rats with chronic SCI to determine if multiple-dosing regimens enhance motor improvement. Chronic SCI rats were randomized and infused with vehicle (vehicle), single MSC injection at week 6 (MSC-1) or repeatedly injections of MSCs at 6, 7, and 8 weeks (MSC-3) after SCI induction. In addition, a single high dose of MSCs (HD-MSC) equivalent to thrice the single dose was infused at week 6. Locomotor function, light and electron microscopy, immunohistochemistry and ex vivo diffusion tensor imaging were performed. Repeated infusion of MSCs (MSC-3) provided the greatest functional recovery compared to single and single high-dose infusions. The density of remyelinated axons in the injured spinal cord was the greatest in the MSC-3 group, followed by the MSC-1, HD-MSC and vehicle groups. Increased sprouting of the corticospinal tract and serotonergic axon density was the greatest in the MSC-3 group, followed by MSC-1, HD-MSC, and vehicle groups. Repeated infusion of MSCs over three weeks resulted in greater functional improvement than single administration of MSCs, even when the number of infused cells was tripled. MSC-treated rats showed axonal sprouting and remyelination in the chronic phase of SCI.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Ratos , Animais , Infusões Intravenosas , Imagem de Tensor de Difusão , Traumatismos da Medula Espinal/terapia , Medula Espinal/fisiologia , Tratos Piramidais , Recuperação de Função Fisiológica/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos
6.
No Shinkei Geka ; 51(3): 390-396, 2023 May.
Artigo em Japonês | MEDLINE | ID: mdl-37211727

RESUMO

Since the beginning of the 21st century, as intraoperative monitoring has been steadily spreading in Japan and globally, the values of motor-evoked potentials, visual-evoked potentials, and cortical-evoked potentials have been described. There are a wide variety of monitoring methods; the diseases handled are not limited to brain lesions, but extend also to spinal cord and spinal lesions; and there are many problems that have not yet been solved. Possible precautions are indicated by means of a video of an actual case site. Considerations are presented regarding the setting of this monitoring method, utilized in relatively frequent diseases and associated intraoperative judgments.


Assuntos
Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Humanos , Potenciais Somatossensoriais Evocados/fisiologia , Potencial Evocado Motor/fisiologia , Medula Espinal/fisiologia , Medula Espinal/cirurgia , Monitorização Intraoperatória/métodos , Japão
7.
Am J Physiol Gastrointest Liver Physiol ; 324(6): G466-G475, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37096901

RESUMO

The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats. hM3Dq or hM4Di was expressed in neurons of the A11 region and/or the raphe nuclei that send output to the lumbosacral defecation center. Immunohistological and functional experiments revealed that both the A11 region and the raphe nuclei directly connected with the lumbosacral spinal cord through descending pathways composed of stimulatory monoaminergic neurons. Stimulation of the hM3Dq-expressing neurons in the A11 region or the raphe nuclei enhanced colorectal motility only when GABAergic transmission in the lumbosacral spinal cord was blocked by bicuculline. Experiments using inhibitory hM4Di-expressing rats revealed that enhancement of colorectal motility caused by noxious stimuli in the colon is mediated by both the A11 region and the raphe nuclei. Furthermore, suppression of the A11 region and/or the raphe nuclei significantly inhibited water avoidance stress-induced defecation. These findings demonstrate that the A11 region and the raphe nuclei play an essential role in the regulation of colorectal motility. This is important because brain regions that mediate both intracolonic noxious stimuli-induced defecation and stress-induced defecation have been clarified for the first time.NEW & NOTEWORTHY The A11 region and the raphe nuclei, constituting descending pain inhibitory pathways, are related to both intracolonic noxious stimuli-induced colorectal motility and stress-induced defecation. Our findings may provide an explanation for the concurrent appearance of abdominal pain and defecation disorders in patients with irritable bowel syndrome. Furthermore, overlap of the pathway controlling colorectal motility with the pathway mediating stress responses may explain why stress exacerbates bowel symptoms.


Assuntos
Neoplasias Colorretais , Núcleos da Rafe , Animais , Ratos , Bulbo , Núcleos da Rafe/fisiologia , Medula Espinal/fisiologia
8.
J Smooth Muscle Res ; 59: 28-33, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37100618

RESUMO

Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous system. Noxious stimuli in the colorectum of anesthetized male rats enhance colorectal motility by activating monoaminergic neurons in descending pain inhibitory pathways from the brainstem to the lumbosacral spinal cord. These monoaminergic neurons release serotonin and dopamine into the lumbosacral spinal cord, resulting in the increment of colorectal motility. In female rats, in contrast, noxious stimuli in the colorectum have no effect on colorectal motility. We clarified that GABAergic inhibition in the lumbosacral spinal cord masks the enhancement of colorectal motility induced by monoamines in female animals. Considering that IBS patients often show visceral hypersensitivity and hyperalgesia, our studies suggest that differences in the descending neurons that respond to painful stimuli are involved in various sex differences in abnormal bowel habits.


Assuntos
Neoplasias Colorretais , Síndrome do Intestino Irritável , Feminino , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Caracteres Sexuais , Medula Espinal/fisiologia
9.
Neuromodulation ; 26(5): 1102-1108, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37086218

RESUMO

OBJECTIVES: Spinal cord stimulation (SCS) is burdened with surgical complications that may require one or several surgical revision(s), challenging its risk/benefit ratio and cost-effectiveness. Our objective was to evaluate its outcome and efficacy after one or more SCS surgical revisions. MATERIALS AND METHODS: We identified and retrospectively analyzed 116 patients treated by tonic paresthesia-based SCS who experienced one or more complication(s) requiring at least one surgical revision. Data collected included initial indication, revision indication, number of revisions, and lead design (paddle or percutaneous). Outcome after SCS revision was evaluated by pain intensity decrease (comparing baseline and postrevision Numerical Rating Scale [NRS] scores) and percentage of patients reporting pain relief ≥50%. Outcome was analyzed according to the number of surgical revisions and the revision indications. RESULTS: Most of the patients (61%) underwent only one revision (mean delay after implantation 44 months). The most frequent causes of revisions were hardware dysfunction (32%), lead migration (23%), and infection (18%). Revision(s) repaired the SCS issue in 87% of the cases. One year after the first revision, 82% of the patients reported pain relief ≥50%, and the mean NRS decrease was 4.0 compared with baseline (p < 0.001). Benefit of SCS revision tended to decrease with the number of revisions but did not differ across revision indications. No serious surgical complications related to the revision occurred, except for three hematomas occurring after repeated revisions. CONCLUSIONS: Our data suggest that surgical revision of SCS system is safe and led to significant pain relief in most of the cases, provided that the initial indication was good and that the previous stimulation was effective. However, success of SCS revision decreases with the number of revisions.


Assuntos
Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/efeitos adversos , Reoperação , Estudos Retrospectivos , Manejo da Dor , Dor/etiologia , Resultado do Tratamento , Medula Espinal/fisiologia
10.
Zoology (Jena) ; 157: 126076, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842298

RESUMO

The evolutionary transformation of limb morphology to the four-segmented pantograph of therians is among the milestones of mammalian evolution. But, it is still unknown if changes of the mechanical limb function were accompanied by corresponding changes in development and sensorimotor control. The impressive locomotor performance of mammals leaves no doubt about the high integration of pattern formation, neural control and mechanics. But, deviations from normal intra- and interlimb coordination (spatial and temporal) become evident in the presence of perturbations. We induced a perturbation in the development of the neural circuits of the spinal cord of mice (Mus musculus) using a deletion of the Wilms tumor suppressor gene Wt1 in a subpopulation of dI6 interneurons. These interneurons are assumed to participate in the intermuscular coordination within the limb and in left-right-coordination between the limbs. We describe the locomotor kinematics in mice with conditional Wt1 knockout and compare them to mice without Wt1 deletion. Unlike knockout neonates, knockout adult mice do not display severe deviations from normal (=control group) interlimb coordination, but the coordinated protraction and retraction of the limbs is altered. The forelimbs are more affected by deviations from the control than the hindlimbs. This observation appears to reflect a different degree of integration and resistance against the induced perturbation between the limbs. Interestingly, the observed effects are similar to locomotor deficits reported to arise when sensory feedback from proprioceptors or cutaneous receptors is impaired. A putative participation of Wt1 positive dI6 interneurons in sensorimotor integration is therefore considered.


Assuntos
Locomoção , Medula Espinal , Animais , Camundongos , Locomoção/fisiologia , Fenômenos Biomecânicos , Membro Posterior/fisiologia , Medula Espinal/fisiologia , Extremidades/fisiologia , Mamíferos
11.
J Neurosci ; 43(3): 419-432, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36639888

RESUMO

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency and minute ventilation were significantly increased when CEES was applied dorsally to the C2-C6 region of the cervical spinal cord. By injecting pseudorabies virus into the diaphragm and using c-Fos activity to identify neurons activated during CEES, we found neurons in the dorsal horn of the cervical spinal cord in which c-Fos and pseudorabies were co-localized, and these neurons expressed somatostatin (SST). Using dual viral infection to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD), hM4D(Gi), selectively in SST-positive cells, we inhibited SST-expressing neurons by administering Clozapine N-oxide (CNO). During CNO-mediated inhibition of SST-expressing cervical spinal neurons, the respiratory excitation elicited by CEES was diminished. Thus, dorsal cervical epidural stimulation activated SST-expressing neurons in the cervical spinal cord, likely interneurons, that communicated with the respiratory pattern generating network to effect changes in ventilation.SIGNIFICANCE STATEMENT A network of pontomedullary neurons within the brainstem generates respiratory behaviors that are susceptible to modulation by a variety of inputs; spinal sensory and motor circuits modulate and adapt this output to meet the demands placed on the respiratory system. We explored dorsal cervical epidural electrical stimulation (CEES) excitation of spinal circuits to increase ventilation in rats. We identified dorsal somatostatin (SST)-expressing neurons in the cervical spinal cord that were activated (c-Fos-positive) by CEES. CEES no longer stimulated ventilation during inhibition of SST-expressing spinal neuronal activity, thereby demonstrating that spinal SST neurons participate in the activation of respiratory circuits affected by CEES. This work establishes a mechanistic foundation to repurpose a clinically accessible neuromodulatory therapy to activate respiratory circuits and stimulate ventilation.


Assuntos
Medula Cervical , Neurônios , Taxa Respiratória , Animais , Feminino , Masculino , Ratos , Medula Cervical/fisiologia , Estimulação Elétrica/métodos , Neurônios/fisiologia , Proteínas Proto-Oncogênicas c-fos , Somatostatina/metabolismo , Somatostatina/farmacologia , Medula Espinal/fisiologia , Taxa Respiratória/fisiologia
12.
J Neurophysiol ; 129(2): 455-464, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695529

RESUMO

Moderate acute intermittent hypoxia (mAIH) elicits a form of phrenic motor plasticity known as phrenic long-term facilitation (pLTF), which requires spinal 5-HT2 receptor activation, ERK/MAP kinase signaling, and new brain-derived neurotrophic factor (BDNF) synthesis. New BDNF protein activates TrkB receptors that normally signal through PKCθ to elicit pLTF. Phrenic motor plasticity elicited by spinal drug administration (e.g., BDNF) is referred to by a more general term: phrenic motor facilitation (pMF). Although mild systemic inflammation elicited by a low lipopolysaccharide (LPS) dose (100 µg/kg; 24 h prior) undermines mAIH-induced pLTF upstream from BDNF protein synthesis, it augments pMF induced by spinal BDNF administration through unknown mechanisms. Here, we tested the hypothesis that mild inflammation shifts BDNF/TrkB signaling from PKCθ to alternative pathways that enhance pMF. We examined the role of three known signaling pathways associated with TrkB (MEK/ERK MAP kinase, PI3 kinase/Akt, and PKCθ) in BDNF-induced pMF in anesthetized, paralyzed, and ventilated Sprague Dawley rats 24 h post-LPS. Spinal PKCθ inhibitor (TIP) attenuated early BDNF-induced pMF (≤30 min), with minimal effect 60-90 min post-BDNF injection. In contrast, MEK inhibition (U0126) abolished BDNF-induced pMF at 60 and 90 min. PI3K/Akt inhibition (PI-828) had no effect on BDNF-induced pMF at any time. Thus, whereas BDNF-induced pMF is exclusively PKCθ-dependent in normal rats, MEK/ERK is recruited by neuroinflammation to sustain, and even augment downstream plasticity. Because AIH is being developed as a therapeutic modality to restore breathing in people living with multiple neurological disorders, it is important to understand how inflammation, a common comorbidity in many traumatic or degenerative central nervous system disorders, impacts phrenic motor plasticity.NEW & NOTEWORTHY We demonstrate that even mild systemic inflammation shifts signaling mechanisms giving rise to BDNF-induced phrenic motor plasticity. This finding has important experimental, biological, and translational implications, particularly since BDNF-dependent spinal plasticity is being translated to restore breathing and nonrespiratory movements in diverse clinical disorders, such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS).


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Medula Espinal , Ratos , Animais , Ratos Sprague-Dawley , Medula Espinal/fisiologia , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos , Hipóxia/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Nervo Frênico/fisiologia , Plasticidade Neuronal
13.
J Neurophysiol ; 129(1): 66-82, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36417309

RESUMO

Although epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. We hypothesized that lateral stimulation over the dorsal root entry zone would be most effective and responses would be strongest in the muscles innervated by the stimulated segment. Twenty-six people undergoing clinically indicated cervical spine surgery consented to mapping of motor responses. During surgery, stimulation was performed in midline and lateral positions at multiple exposed segments; six arm and three leg muscles were recorded on each side of the body. Across all segments and muscles tested, lateral stimulation produced stronger muscle responses than midline despite similar latency and shape of responses. Muscles innervated at a cervical segment had the largest responses from stimulation at that segment, but responses were also observed in muscles innervated at other cervical segments and in leg muscles. The cervical responses were clustered in rostral (C4-C6) and caudal (C7-T1) cervical segments. Strong responses to lateral stimulation are likely due to the proximity of stimulation to afferent axons. Small changes in response sizes to stimulation of adjacent cervical segments argue for local circuit integration, and distant muscle responses suggest activation of long propriospinal connections. This map can help guide cervical stimulation to improve arm and hand function.NEW & NOTEWORTHY A map of muscle responses to cervical epidural stimulation during clinically indicated surgery revealed strongest activation when stimulating laterally compared to midline and revealed differences to be weaker than expected across different segments. In contrast, waveform shapes and latencies were most similar when stimulating midline and laterally, indicating activation of overlapping circuitry. Thus, a map of the cervical spinal cord reveals organization and may help guide stimulation to activate arm and hand muscles strongly and selectively.


Assuntos
Traumatismos da Medula Espinal , Estimulação da Medula Espinal , Animais , Humanos , Eletromiografia , Medula Espinal/fisiologia , Músculo Esquelético/fisiologia , Membro Anterior , Estimulação Elétrica
14.
J Physiol ; 601(15): 3103-3121, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36409303

RESUMO

Seventy years ago, Hodgkin and Huxley published the first mathematical model to describe action potential generation, laying the foundation for modern computational neuroscience. Since then, the field has evolved enormously, with studies spanning from basic neuroscience to clinical applications for neuromodulation. Computer models of neuromodulation have evolved in complexity and personalization, advancing clinical practice and novel neurostimulation therapies, such as spinal cord stimulation. Spinal cord stimulation is a therapy widely used to treat chronic pain, with rapidly expanding indications, such as restoring motor function. In general, simulations contributed dramatically to improve lead designs, stimulation configurations, waveform parameters and programming procedures and provided insight into potential mechanisms of action of electrical stimulation. Although the implementation of neural models are relentlessly increasing in number and complexity, it is reasonable to ask whether this observed increase in complexity is necessary for improved accuracy and, ultimately, for clinical efficacy. With this aim, we performed a systematic literature review and a qualitative meta-synthesis of the evolution of computational models, with a focus on complexity, personalization and the use of medical imaging to capture realistic anatomy. Our review showed that increased model complexity and personalization improved both mechanistic and translational studies. More specifically, the use of medical imaging enabled the development of patient-specific models that can help to transform clinical practice in spinal cord stimulation. Finally, we combined our results to provide clear guidelines for standardization and expansion of computational models for spinal cord stimulation.


Assuntos
Dor Crônica , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Dor Crônica/terapia , Simulação por Computador , Estimulação Elétrica , Medula Espinal/fisiologia
15.
Vascular ; 31(2): 250-256, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34875933

RESUMO

OBJECTIVE: This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. METHODS: The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru - T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. RESULTS: After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference (p < 0.05). CONCLUSION: Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.


Assuntos
Doenças da Aorta , Arteriopatias Oclusivas , Isquemia do Cordão Espinal , Ratos , Animais , Isquemia do Cordão Espinal/etiologia , Isquemia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Medula Espinal/fisiologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aorta Torácica/patologia , Doenças da Aorta/patologia , Necrose/patologia
16.
J Am Soc Nephrol ; 33(12): 2194-2210, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36253054

RESUMO

BACKGROUND: The kidneys critically contribute to body homeostasis under the control of the autonomic nerves, which enter the kidney along the renal vasculature. Although the renal sympathetic and sensory nerves have long been confirmed, no significant anatomic evidence exists for renal parasympathetic innervation. METHODS: We identified cholinergic nerve varicosities associated with the renal vasculature and pelvis using various anatomic research methods, including a genetically modified mouse model and immunostaining. Single-cell RNA sequencing (scRNA-Seq) was used to analyze the expression of AChRs in the renal artery and its segmental branches. To assess the origins of parasympathetic projecting nerves of the kidney, we performed retrograde tracing using recombinant adeno-associated virus (AAV) and pseudorabies virus (PRV), followed by imaging of whole brains, spinal cords, and ganglia. RESULTS: We found that cholinergic axons supply the main renal artery, segmental renal artery, and renal pelvis. On the renal artery, the newly discovered cholinergic nerve fibers are separated not only from the sympathetic nerves but also from the sensory nerves. We also found cholinergic ganglion cells within the renal nerve plexus. Moreover, the scRNA-Seq analysis suggested that acetylcholine receptors (AChRs) are expressed in the renal artery and its segmental branches. In addition, retrograde tracing suggested vagus afferents conduct the renal sensory pathway to the nucleus of the solitary tract (NTS), and vagus efferents project to the kidney. CONCLUSIONS: Cholinergic nerves supply renal vasculature and renal pelvis, and a vagal brain-kidney axis is involved in renal innervation.


Assuntos
Rim , Sistema Nervoso Simpático , Camundongos , Animais , Sistema Nervoso Simpático/fisiologia , Medula Espinal/fisiologia , Pelve , Colinérgicos
17.
Neuromodulation ; 25(5): 719-723, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35803678

RESUMO

OBJECTIVES: Spinal cord stimulation (SCS) is increasingly utilized in the treatment of multiple chronic pain conditions. However, patients will continue to experience other medical issues and the potential for future magnetic resonance imaging (MRI) needs must not be overlooked. SCS devices have device-specific MRI conditional labeling and if impedances are elevated the patient may not be able to obtain an MRI. With 10 kHz SCS devices specifically, an impedance value above 10,000 ohms (Ω) is MRI ineligible. The primary objective of this article was to report the incidence of elevated impedances with a multilumen lead design per electrode, per lead, and to describe the total number of MRI ineligible patients due to elevated impedances using 10 kHz SCS cutoff values. The secondary objective was to determine whether certain patient demographics or surgery characteristics put patients at increased risk of elevated impedances. MATERIALS AND METHODS: We performed a retrospective review of 327 patients who were implanted with a 10 kHz SCS device between January 2015 and November 2020. Regression models were fitted to determine associations between MRI ineligibility status with clinical characteristics including age, sex, BMI, lead location, implantable pulse generator (IPG) location, and time since implant. RESULTS: We found elevated impedances with subsequent MRI ineligibility in 13 patients (4.0%). Regression analysis did not identify any associations with MRI ineligibility and patient risk factors including age, sex, body mass index, lead location, IPG location, and follow-up time since implant. CONCLUSION: We found the prevalence of elevated impedances above 10,000 Ω to be 4% of implanted patients. This information is important for patients and physicians alike and should be considered when device selection is occurring in the pre-operative visits.


Assuntos
Dor Crônica , Estimulação da Medula Espinal , Dor Crônica/diagnóstico por imagem , Dor Crônica/epidemiologia , Dor Crônica/terapia , Impedância Elétrica , Humanos , Imageamento por Ressonância Magnética , Prevalência , Estudos Retrospectivos , Medula Espinal/fisiologia , Estimulação da Medula Espinal/métodos
18.
Neuromodulation ; 25(5): 763-774, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35803681

RESUMO

OBJECTIVES: To investigate the long-term changes in thecal sac compression following T9 paddle lead spinal cord stimulation (SCS) using three-dimensional myelographic computed tomography (CT). MATERIALS AND METHODS: Seventeen patients with five-column paddle lead SCS at T9 underwent three-dimensional myelographic CT scans preoperatively, immediately after surgery, and after an average of 11 months. The cross-sectional areas of thecal sac and spinal cord and the widths of anterior and posterior cerebrospinal fluid (CSF) spaces were repeatedly measured and compared. The contact angle of the lead with long-term pain relief was assessed. RESULTS: The cross-sectional areas of thecal sac and spinal cord decreased significantly after lead placement (30.47 ± 9.21% and 4.71 ± 9.84%, respectively). Even after 11 months, a significant reduction was found with the preoperative values (17.97 ± 12.32% and 2.88 ± 7.09%). The widths of anterior and posterior CSF spaces decreased significantly after surgery (43.53 ± 13.17% and 57.13 ± 13.17%, respectively) and the severe decrease persisted long-term (29.13 ± 21.54% and 50.99 ± 16.07%). The average pain relief was 42.27 ± 17.50% with no correlation between the rate of reduction in cross-sectional areas of thecal sac and the widths of CSF spaces. CONCLUSIONS: Significant early reduction and late partial restoration occurred in the thecal sac and spinal cord and the width of the anterior and posterior CSF spaces in the T9 5-column paddle lead SCS. Thecal sac compromise was expected to some extent after paddle lead implantation, but the degree is significant, and the cross-sectional area of the spinal cord as well as the thecal sac is affected. Fortunately, these anatomical changes did not cause any clinical problems except for intercostal root irritation. The shape and flat contours of the five-column paddle leads clearly affected the results.


Assuntos
Estimulação da Medula Espinal , Seguimentos , Humanos , Mielografia/métodos , Dor , Medula Espinal/fisiologia , Estimulação da Medula Espinal/métodos , Tomografia Computadorizada por Raios X/métodos
19.
Neuron ; 110(14): 2206-2208, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35863318

RESUMO

How the spinal cord transmits heat signals from the periphery to the brain remains unclear. In this issue of Neuron, Wang et al. (2022) identify a population of spinal cord neurons functioning in this pathway.


Assuntos
Temperatura Alta , Células do Corno Posterior , Humanos , Neurônios , Dor/metabolismo , Células do Corno Posterior/fisiologia , Receptor ErbB-4/metabolismo , Medula Espinal/fisiologia , Corno Dorsal da Medula Espinal
20.
Sensors (Basel) ; 22(10)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35632249

RESUMO

The spinal cord is a major structure of the central nervous system allowing, among other things, the transmission of afferent sensory and efferent motor information. During spinal surgery, such as scoliosis correction, this structure can be damaged, resulting in major neurological damage to the patient. To date, there is no direct way to monitor the oxygenation of the spinal cord intraoperatively to reflect its vitality. This is essential information that would allow surgeons to adapt their procedure in case of ischemic suffering of the spinal cord. We report the development of a specific device to monitor the functional status of biological tissues with high resolution. The device, operating with multiple wavelengths, uses Near-InfraRed Spectroscopy (NIRS) in combination with other additional sensors, including ElectroNeuroGraphy (ENG). In this paper, we focused primarily on aspects of the PhotoPlethysmoGram (PPG), emanating from four different light sources to show in real time and record biological signals from the spinal cord in transmission and reflection modes. This multispectral system was successfully tested in in vivo experiments on the spinal cord of a pig for specific medical applications.


Assuntos
Monitorização Intraoperatória , Medula Espinal , Animais , Hemodinâmica/fisiologia , Humanos , Monitorização Intraoperatória/métodos , Monitorização Fisiológica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/fisiologia , Suínos
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