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1.
Neurol India ; 70(2): 767-771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35532656

RESUMO

Melioidosis is gram-negative bacterial infection endemic in parts of Australia and Asia with significant morbidity and mortality. It is acquired in wet rainy seasons through occupational and recreational activities. Although central nervous system (CNS) involvement is seen in less than 10%, it can have severe sequelae. MRI (magnetic resonance imaging) findings in reported cases have shown predominant brain stem and frontoparietal involvement. We present three pediatric cases of neuromelioidosis in which corticospinal tract involvement was a characteristic finding.


Assuntos
Melioidose , Tratos Piramidais , Ásia , Criança , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Melioidose/patologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia
3.
Front Neural Circuits ; 16: 847100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463202

RESUMO

Removal of the monosynaptic corticospinal pathway (CSP) terminating within the forelimb segments severely impairs manual dexterity. Functional recovery from the monosynaptic CSP lesion can be achieved through the remaining multisynaptic CSP toward the forelimb segments. In the present study, we applied retrograde transsynaptic labeling with rabies virus to a monkey model of spinal cord injury. By injecting the virus into the spinal forelimb segments immediately after the monosynaptic CSP lesion, we showed that the contralateral primary motor cortex (M1), especially its caudal and bank region (so-called "new" M1), was the principal origin of the CSP linking the motor cortex to the spinal forelimb segments disynaptically (disynaptic CSP). This forms a striking contrast to the architecture of the monosynaptic CSP that involves extensively other motor-related areas, together with M1. Next, the rabies injections were made at the recovery period of 3 months after the monosynaptic CSP lesion. The second-order labeled neurons were located in the ipsilateral as well as in the contralateral "new" M1. This indicates that the disynaptic CSP input from the ipsilateral "new" M1 is recruited during the motor recovery from the monosynaptic CSP lesion. Our results suggest that the disynaptic CSP is reorganized to connect the ipsilateral "new" M1 to the forelimb motoneurons for functional compensation after the monosynaptic CSP lesion.


Assuntos
Tratos Piramidais , Traumatismos da Medula Espinal , Animais , Membro Anterior/fisiologia , Macaca , Neurônios Motores/fisiologia , Tratos Piramidais/fisiologia , Medula Espinal/fisiologia
4.
J Neurosci ; 42(18): 3716-3732, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35361703

RESUMO

The limited ability for axonal repair after spinal cord injury underlies long-term functional impairment. Dual leucine-zipper kinase [DLK; MAP kinase kinase kinase 12; MAP3K12] is an evolutionarily conserved MAP3K implicated in neuronal injury signaling from Caenorhabditis elegans to mammals. However, whether DLK or its close homolog leucine zipper kinase (LZK; MAP3K13) regulates axonal repair in the mammalian spinal cord remains unknown. Here, we assess the role of endogenous DLK and LZK in the regeneration and compensatory sprouting of corticospinal tract (CST) axons in mice of both sexes with genetic analyses in a regeneration competent background provided by PTEN deletion. We found that inducible neuronal deletion of both DLK and LZK, but not either kinase alone, abolishes PTEN deletion-induced regeneration and sprouting of CST axons, and reduces naturally-occurring axon sprouting after injury. Thus, DLK/LZK-mediated injury signaling operates not only in injured neurons to regulate regeneration, but also unexpectedly in uninjured neurons to regulate sprouting. Deleting DLK and LZK does not interfere with PTEN/mTOR signaling, indicating that injury signaling and regenerative competence are independently controlled. Together with our previous study implicating LZK in astrocytic reactivity and scar formation, these data illustrate the multicellular function of this pair of MAP3Ks in both neurons and glia in the injury response of the mammalian spinal cord.SIGNIFICANCE STATEMENT Functional recovery after spinal cord injury is limited because of a lack of axonal repair in the mammalian CNS. Dual leucine-zipper kinase (DLK) and leucine zipper kinase (LZK) are two closely related protein kinases that have emerged as regulators of neuronal responses to injury. However, their role in axonal repair in the mammalian spinal cord has not been described. Here, we show that DLK and LZK together play critical roles in axonal repair in the mammalian spinal cord, validating them as potential targets to promote repair and recovery after spinal cord injury. In addition to regulating axonal regeneration from injured neurons, both kinases also regulate compensatory axonal growth from uninjured neurons, indicating a more pervasive role in CNS repair than originally anticipated.


Assuntos
Zíper de Leucina , MAP Quinase Quinase Quinases/metabolismo , Traumatismos da Medula Espinal , Animais , Axônios/fisiologia , Feminino , Leucina/metabolismo , MAP Quinase Quinase Quinases/genética , Masculino , Mamíferos , Camundongos , Regeneração Nervosa/fisiologia , Tratos Piramidais/fisiologia
5.
J Neural Eng ; 19(2)2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35366651

RESUMO

Objective. Transcranial magnetic stimulation (TMS) is an experimental therapy for promoting motor recovery from hemiparesis. At present, hemiparesis patients' responses to TMS are variable. To maximize its therapeutic potential, we need an approach that relates the electrophysiology of motor recovery and TMS. To this end, we propose corticomuscular network (CMN) representing the holistic motor system, including the cortico-cortical pathway, corticospinal tract, and muscle co-activation.Approach. CMN is made up of coherence between pairs of electrode signals and spatial locations of the electrodes. We associated coherence and graph features of CMN with Fugl-Meyer Assessment (FMA) for the upper extremity. Besides, we compared CMN between 8 patients with hemiparesis and 6 healthy controls and contrasted CMN of patients before and after a 1 Hz TMS.Main results. Corticomuscular coherence (CMC) correlated positively with FMA. The regression model between FMA and CMC between five pairs of channels had 0.99 adjusted and ap-value less than 0.01. Compared to healthy controls, CMN of patients tended to be a small-world network and was more interconnected with higher CMC. CMC between cortex and triceps brachii long head was higher in patients. 15 min 1 Hz TMS protocol induced coherence changes beyond the stimulation side and had a limited impact on CMN parameters that are related to motor recovery.Significance. CMN is a potential clinical approach to quantify rehabilitating progress. It also sheds light on the desirable electrophysiological effects of TMS based on which rehabilitating strategies can be optimized.


Assuntos
Córtex Motor , Estimulação Magnética Transcraniana , Eletromiografia , Humanos , Córtex Motor/fisiologia , Paresia/diagnóstico , Tratos Piramidais/fisiologia , Estimulação Magnética Transcraniana/métodos
6.
Pediatr Phys Ther ; 34(2): 268-276, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385465

RESUMO

PURPOSE: Perinatal brain injury is a primary cause of cerebral palsy, a condition resulting in lifelong motor impairment. Infancy is an important period of motor system development, including development of the corticospinal tract (CST), the primary pathway for cortical movement control. The interaction between perinatal stroke recovery, CST organization, and resultant motor outcome in infants is not well understood. METHODS: Here, we present a protocol for multimodal longitudinal assessment of brain development and motor function following perinatal brain injury using transcranial magnetic stimulation and magnetic resonance imaging to noninvasively measure CST functional and structural integrity across multiple time points in infants 3 to 24 months of age. We will further assess the association between cortical excitability, integrity, and motor function. DISCUSSION: This protocol will identify bioindicators of motor outcome and neuroplasticity and subsequently inform early detection, diagnosis, and intervention strategies for infants with perinatal stroke, brain bleeds, and related diagnoses.


Assuntos
Lesões Encefálicas , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Humanos , Lactente , Imageamento por Ressonância Magnética , Tratos Piramidais/diagnóstico por imagem , Estimulação Magnética Transcraniana
7.
J Integr Neurosci ; 21(2): 50, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35364638

RESUMO

BACKGROUND: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. METHODS: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. RESULTS: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. CONCLUSIONS: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Tratos Piramidais , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana , Resultado do Tratamento , Extremidade Superior
8.
Med Sci Monit ; 28: e936417, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35431312

RESUMO

Limb-kinetic apraxia (LKA) is an execution disorder of movements caused by an injury to the secondary motor area (the supplementary motor area and premotor cortex) with preservation of an intact corticospinal tract (CST). A precise diagnosis of LKA is often limited because it is made based on the clinical observation of movement characteristics with confirmation of the CST state, and no specific clinical assessment tools for LKA have been developed. Diffusion tensor tractography (DTT) enables a three-dimensional estimation of the neural tracts related to LKA, such as the CST and corticofugal tract from the secondary motor area. This article reviewed 5 DTT-based studies on LKA-related neural tracts in stroke patients. These studies suggest that DTT could be a useful diagnostic tool for LKA along with previous diagnostic tools, such as brain magnetic resonance imaging and transcranial magnetic stimulation. In particular, DTT for the affected corticofugal tract can provide useful evidence for diagnosing LKA when clinicians cannot observe the movement characteristics because of severe weakness after a severe injury to the affected CST. Furthermore, a reviewed study suggested that LKA might be related to the unaffected neural tracts for motor function when the affected neural tracts were severely injured. This review summarizes the role of DTT in the diagnosis of LKA in stroke patients.


Assuntos
Apraxias , Córtex Motor , Acidente Vascular Cerebral , Apraxias/complicações , Apraxias/diagnóstico por imagem , Apraxias/patologia , Imagem de Tensor de Difusão , Humanos , Córtex Motor/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
9.
Biomed Pharmacother ; 149: 112797, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35279596

RESUMO

Intracerebral hemorrhage (ICH) has a high mortality and disability rate. Fewer studies focus on white matter injury (WMI) after ICH, especially the corticospinal tract (CST) injury located in the spinal cord, which correlates with motor impairments. Recent studies have shown that gut microbiota dysbiosis occurs after ICH. Furthermore, NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. However, no direct and causal correlation among NLRP3 inflammasome inhibition, altered gut microbiota, and CST injury following ICH has been reported. This study aimed to investigate the effect of MCC950, a selective NLRP3 inflammasome inhibitor, on the gut microbiota and CST injury after ICH. We observed that compared with the sham group, the members of Firmicutes, such as Faecalibaculum and Dubosiella, were depleted in the ICH + Vehicle group, whereas the members of Proteobacteria and Campilobacterota were enriched, such as Enterobacter and Helicobacter. After treatment with MCC950, the Bacteroides, Bifidobacterium and Paenibacillus were relatively abundant in the gut flora of mice. Moreover, we observed CST injury located in cervical enlargement of the spinal cord, and MCC950 alleviated it. Furthermore, treatment with MCC950 decreased the mNSS score and brain water content in ICH. Taken together, the present study showed that MCC950 modulated gut microbiota, effectively attenuated CST injury located in cervical enlargement of the spinal cord, and ameliorated neurological deficits after ICH. This study provided a novel report that links NLRP3 inflammasome inhibition, gut microbiota alteration and CST injury following ICH and profound implications for ICH treatment.


Assuntos
Lesões Encefálicas , Microbioma Gastrointestinal , Animais , Lesões Encefálicas/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Modelos Animais de Doenças , Inflamassomos , Inflamação/complicações , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Tratos Piramidais
10.
Eur J Neurosci ; 55(7): 1810-1824, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35274383

RESUMO

Neural interactions between upper and lower limbs underlie motor coordination in humans. Specifically, upper limb voluntary muscle contraction can facilitate spinal and corticospinal excitability of the lower limb muscles. However, little remains known on the involvement of somatosensory information in arm-leg neural interactions. Here, we investigated effects of voluntary and electrically induced wrist flexion on corticospinal excitability and somatosensory information processing of the lower limbs. In Experiment 1, we measured transcranial magnetic stimulation (TMS)-evoked motor evoked potentials (MEPs) of the resting soleus (SOL) muscle at rest or during voluntary or neuromuscular electrical stimulation (NMES)-induced wrist flexion. The wrist flexion force was matched to 10% of the maximum voluntary contraction (MVC). We found that SOL MEPs were significantly increased during voluntary, but not NMES-induced, wrist flexion, compared to the rest (P < .001). In Experiment 2, we examined somatosensory evoked potentials (SEPs) following tibial nerve stimulation under the same conditions. The results showed that SEPs were unchanged during both voluntary and NMES-induced wrist flexion. In Experiment 3, we examined the modulation of SEPs during 10%, 20% and 30% MVC voluntary wrist flexion. During 30% MVC voluntary wrist flexion, P50-N70 SEP component was significantly attenuated compared to the rest (P = .003). Our results propose that the somatosensory information generated by NMES-induced upper limb muscle contractions may have a limited effect on corticospinal excitability and somatosensory information processing of the lower limbs. However, voluntary wrist flexion modulated corticospinal excitability and somatosensory information processing of the lower limbs via motor areas.


Assuntos
Potencial Evocado Motor , Contração Muscular , Estimulação Elétrica , Eletromiografia , Potencial Evocado Motor/fisiologia , Humanos , Extremidade Inferior/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Tratos Piramidais/fisiologia , Estimulação Magnética Transcraniana , Extremidade Superior
11.
Am J Phys Med Rehabil ; 101(4): 353-357, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35302528

RESUMO

OBJECTIVES: Less is known how dysphagia affects older patients without neurologic diseases and whether the symptoms of dysphagia have any association with impaired central control of swallowing. This study investigated the state of the corticobulbar tract, the surrogate marker for the central control of swallowing, in older dysphagic patients without any neurologic diseases, using diffusion tensor tractography. DESIGN: This retrospective observational study was conducted at a tertiary university hospital including 10 patients 60 yrs or older with oropharyngeal dysphagia without neurological disease and 11 age- and sex-matched control participants. The corticobulbar tract was reconstructed, and the fractional anisotropy and tract volume were measured using diffusion tensor tractography. RESULTS: The corticobulbar tracts of the dysphagia group were narrowed and not reconstructed by their configurations and had lower fractional anisotropy and tract volume values when compared with those of control group. Significant asymmetry between the left and the right corticobulbar tract hemispheres was found in the dysphagia group, whereas no asymmetry was found in the control group. CONCLUSIONS: A deteriorated corticobulbar tract could be associated with the development of dysphagia in older adults without neurological diseases. Our findings might help establish more appropriate treatment strategies, such as targeted neuromodulation therapies in the future.


Assuntos
Transtornos de Deglutição , Doenças do Sistema Nervoso , Idoso , Anisotropia , Deglutição , Transtornos de Deglutição/etiologia , Imagem de Tensor de Difusão , Humanos , Doenças do Sistema Nervoso/complicações , Tratos Piramidais/diagnóstico por imagem
12.
J Neurosci ; 42(15): 3150-3164, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35241490

RESUMO

The control of contraction strength is a key part of movement control. In primates, both corticospinal and reticulospinal cells provide input to motoneurons. Corticospinal discharge is known to correlate with force, but there are no previous reports of how reticular formation (RF) activity modulates with different contractions. Here we trained two female macaque monkeys (body weight, 5.9-6.9 kg) to pull a handle that could be loaded with 0.5-6 kg weights and recorded from identified pyramidal tract neurons (PTNs) in primary motor cortex and RF cells during task performance. Population-averaged firing rate increased monotonically with higher force for the RF, but showed a complex profile with little net modulation for PTNs. This reflected a more heterogeneous profile of rate modulation across the PTN population, leading to cancellation in the average. Linear discriminant analysis classified the force based on the time course of rate modulation equally well for PTNs and RF cells. Peak firing rate had significant linear correlation with force for 43 of 92 PTNs (46.7%) and 21 of 46 RF cells (43.5%). For almost all RF cells (20 of 21), the correlation coefficient was positive; similar numbers of PTNs (22 vs 21) had positive versus negative coefficients. Considering the timing of force representation, similar fractions (PTNs: 61.2%; RF cells: 55.5%) commenced coding before the onset of muscle activity. We conclude that both corticospinal and reticulospinal tracts contribute to the control of contraction force; the reticulospinal tract seems to specify an overall signal simply related to force, whereas corticospinal cell activity would be better suited for fine-scale adjustments.SIGNIFICANCE STATEMENT For the first time, we compare the coding of force for corticospinal and reticular formation cells in awake behaving monkeys, over a wide range of contraction strengths likely to come close to maximum voluntary contraction. Both cortical and brainstem systems coded similarly well for force, but whereas reticular formation cells carried a simple uniform signal, corticospinal neurons were more heterogeneous. This may reflect a role in the gross specification of a coordinated movement, versus more fine-grained adjustments around individual joints.


Assuntos
Córtex Motor , Animais , Feminino , Macaca , Córtex Motor/fisiologia , Neurônios Motores/fisiologia , Contração Muscular/fisiologia , Tratos Piramidais/fisiologia , Formação Reticular/fisiologia
13.
Neuroimage Clin ; 33: 102945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35124524

RESUMO

Secondary white matter degeneration is a common occurrence after ischemic stroke, as identified by Diffusion Tensor Imaging (DTI). However, despite recent advances, the time course of the process is not completely understood. The primary aim of this study was to assess secondary degeneration using an approach whereby we create a patient-specific model of damaged fibers based on the volumetric characteristics of lesions. We also examined the effects of secondary degeneration along the modelled streamlines at different distances from the primary infarction using DTI. Eleven patients who presented with upper limb motor deficits at the time of a first-ever ischemic stroke were included. They underwent scanning at weeks 6 and 29 post-stroke. The fractional anisotropy (FA), mean diffusivity (MD), primary eigenvalue (λ1), and transverse eigenvalue (λ23) were measured. Using regions of interest based on the simulation output, the differences between the modelled fibers and matched contralateral areas were analyzed. The longitudinal change between the two time points and across five distances from the primary lesion was also assessed using the ratios of diffusion quantities (rFA, rMD, rλ1, and rλ23) between the ipsilesional and contralesional hemisphere. At week 6 post-stroke, significantly decreased λ1 was found along the ipsilesional corticospinal tract (CST) with a trend towards lower FA, reduced MD and λ23. At week 29 post-stroke, significantly decreased FA was shown relative to the non-lesioned side, with a trend towards lower λ1, unchanged MD, and higher λ23. Along the ipsilesional tract, the rFA diminished, whereas the rMD, rλ1, and rλ23 significantly increased over time. No significant variations in the time progressive effect with distance were demonstrated. The findings support previously described mechanisms of secondary degeneration and suggest that it spreads along the entire length of a damaged tract. Future investigations using higher-order tractography techniques can further explain the intravoxel alterations caused by ischemic injury.


Assuntos
AVC Isquêmico , Substância Branca , Anisotropia , Imagem de Tensor de Difusão/métodos , Humanos , AVC Isquêmico/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
15.
Clin Neurophysiol ; 136: 1-12, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35131634

RESUMO

OBJECTIVE: The role of ipsilateral motor cortex efferent pathways in the transmission of voluntary command to spinal motor nuclei remains controversial in humans. In healthy subjects, their implication in cortical control is hidden by predominant role of crossed corticospinal tract. However, evidence from electrophysiological and imaging studies suggest that ipsilateral tracts may contribute to functional recovery after unilateral brain damage. This randomized-sham control study aims to explore to what extent ipsilateral tracts from the undamaged hemisphere may strengthen corticospinal control onto spinal motor networks following stroke. METHODS: Anodal transcranial direct current stimulation (tDCS) was combined with monosynaptic H-reflex method to evaluate the variations of reciprocal inhibition (RI) in wrist flexors in 21 stroke participants. RESULTS: Anodal tDCS decreased RI in wrist flexors in stroke participants in both arms. tDCS unmasks an ipsilateral control from the undamaged hemisphere onto spinal motor networks controlling affected arm muscles in stroke participants. In the unaffected (contralateral) arm, effects in stroke participants were opposite to those induced in healthy subjects. CONCLUSIONS: Stimulation of the undamaged cortex in stroke participants induces modulation of ipsilateral motor networks controlling the hemiparetic side. SIGNIFICANCE: Rehabilitation could leverage stimulation of the undamaged hemisphere to enhance motor recovery post stroke.


Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Braço , Potencial Evocado Motor/fisiologia , Humanos , Tratos Piramidais , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Transcraniana por Corrente Contínua/métodos
16.
J Neurosci ; 42(11): 2190-2204, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35135857

RESUMO

Failure of CNS neurons to mount a significant growth response after trauma contributes to chronic functional deficits after spinal cord injury. Activator and repressor screening of embryonic cortical neurons and retinal ganglion cells in vitro and transcriptional profiling of developing CNS neurons harvested in vivo have identified several candidates that stimulate robust axon growth in vitro and in vivo Building on these studies, we sought to identify novel axon growth activators induced in the complex adult CNS environment in vivo We transcriptionally profiled intact sprouting adult corticospinal neurons (CSNs) after contralateral pyramidotomy (PyX) in nogo receptor-1 knock-out mice and found that intact CSNs were enriched in genes in the 3-phosphoinositide degradation pathway, including six 5-phosphatases. We explored whether inositol polyphosphate-5-phosphatase K (Inpp5k) could enhance corticospinal tract (CST) axon growth in preclinical models of acute and chronic CNS trauma. Overexpression of Inpp5k in intact adult CSNs in male and female mice enhanced the sprouting of intact CST terminals after PyX and cortical stroke and sprouting of CST axons after acute and chronic severe thoracic spinal contusion. We show that Inpp5k stimulates axon growth in part by elevating the density of active cofilin in labile growth cones, thus stimulating actin polymerization and enhancing microtubule protrusion into distal filopodia. We identify Inpp5k as a novel CST growth activator capable of driving compensatory axon growth in multiple complex CNS injury environments and underscores the veracity of using in vivo transcriptional screening to identify the next generation of cell-autonomous factors capable of repairing the damaged CNS.SIGNIFICANCE STATEMENT Neurologic recovery is limited after spinal cord injury as CNS neurons are incapable of self-repair post-trauma. In vitro screening strategies exploit the intrinsically high growth capacity of embryonic CNS neurons to identify novel axon growth activators. While promising candidates have been shown to stimulate axon growth in vivo, concomitant functional recovery remains incomplete. We identified Inpp5k as a novel axon growth activator using transcriptional profiling of intact adult corticospinal tract (CST) neurons that had initiated a growth response after pyramidotomy in plasticity sensitized nogo receptor-1-null mice. Here, we show that Inpp5k overexpression can stimulate CST axon growth after pyramidotomy, stroke, and acute and chronic contusion injuries. These data support in vivo screening approaches to identify novel axon growth activators.


Assuntos
Tratos Piramidais , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Feminino , Inositol/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/fisiologia , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Polifosfatos/metabolismo , Tratos Piramidais/fisiologia
17.
J Clin Neurosci ; 98: 29-36, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35131722

RESUMO

Transcranial motor evoked potential (MEP) monitoring, intended to assess cerebral cortical ischemia, may produce false negative results when the stimulation inadvertently activates the deep, subcortical motor pathways. This study examined hand MEP onset latency as a potential means to differentiate superficial versus deep stimulus penetration in surgical patients monitored for cerebral ischemia. Intraoperative MEP data were prospectively collected from 40 patients treated for intracranial aneurysm or carotid stenosis. Onset latencies of hand MEP responses were measured over a range of stimulation intensities from both the contralateral and ipsilateral hand (crossover responses). At the threshold for superficial, cortical stimulation of the contralateral hand, the MEP latency was 26.9 ± 0.4 ms. MEP onset latencies measurements became shorter as stimulation intensities were increased. At the maximum intensity (when crossover response was usually generated), the contralateral hand MEP latency of 22.5 ± 0.3 ms was significantly shorter than at threshold stimulation (p < 0.001). Latency-stimulus intensity plots best fit a 3 parameter hyperbolic decay function (r2 = 0.85 ± 0.02) and revealed a narrow window of acceptable MEP stimuli to obtain superficial cortical activation. Our analysis refutes the utility of the crossover response in reliably gauging depth of activation. Additionally, we found that differentiation between long and short MEP onset latency times may serve as a dependable marker for depth of stimulation. Attention to hand MEP onset latency may reduce inadvertent stimulation of the deep corticospinal tract pathways and avoid false negative MEP recordings during cerebrovascular surgeries.


Assuntos
Isquemia Encefálica , Aneurisma Intracraniano , Isquemia Encefálica/diagnóstico , Potencial Evocado Motor/fisiologia , Mãos , Humanos , Aneurisma Intracraniano/cirurgia , Tratos Piramidais
18.
Phys Med Biol ; 67(6)2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35168220

RESUMO

Robotic cochlear implantation is an effective way to restore the hearing of hearing-impaired patients, and facial nerve recognition is the key to the operation. However, accurate facial nerve segmentation is a challenging task, mainly for two key issues: (1) the facial nerve area is very small in image, and there are many similar areas; (2) low contrast of the border between the facial nerve and the surrounding tissues increases the difficulty. In this work, we propose an end-to-end neural network, called FNSegNet, with two stages to solve these problems. Specifically, in the coarse segmentation stage, we first adopt three search identification modules to capture small objects by expanding the receptive field from high-level features and combine an effective pyramid fusion module to fuse. In the refine segmentation stage, we use a decoupling optimization module to establish the relationship between the central region and the boundary details of facial nerve by decoupling the boundary and center area. Meanwhile, we feed them into a spatial attention module to correct the conflict regions. Extensive experiments on the challenging dataset demonstrate that the proposed FNSegNet significantly improves the segmentation accuracy (0.858 on Dice, 0.363 mm on 95% Hausdorff distance), and reduces the computational complexity (13.33G on FLOPs, 9.86M parameters).


Assuntos
Nervo Facial , Robótica , Nervo Facial/diagnóstico por imagem , Audição , Humanos , Redes Neurais de Computação , Tratos Piramidais
19.
Curr Biol ; 32(7): 1616-1622.e5, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35219429

RESUMO

During motor learning,1 as well as during neuroprosthetic learning,2-4 animals learn to control motor cortex activity in order to generate behavior. Two different populations of motor cortex neurons, intra-telencephalic (IT) and pyramidal tract (PT) neurons, convey the resulting cortical signals within and outside the telencephalon. Although a large amount of evidence demonstrates contrasting functional organization among both populations,5,6 it is unclear whether the brain can equally learn to control the activity of either class of motor cortex neurons. To answer this question, we used a calcium-imaging-based brain-machine interface (CaBMI)3 and trained different groups of mice to modulate the activity of either IT or PT neurons in order to receive a reward. We found that the animals learned to control PT neuron activity faster and better than IT neuron activity. Moreover, our findings show that the advantage of PT neurons is the result of characteristics inherent to this population as well as their local circuitry and cortical depth location. Taken together, our results suggest that the motor cortex is more efficient at controlling the activity of pyramidal tract neurons, which are embedded deep in the cortex, and relaying motor commands outside the telencephalon.


Assuntos
Interfaces Cérebro-Computador , Córtex Motor , Animais , Aprendizagem/fisiologia , Camundongos , Córtex Motor/fisiologia , Neurônios Motores/fisiologia , Tratos Piramidais/fisiologia
20.
Neuroscience ; 485: 53-64, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35031397

RESUMO

Conventional transcutaneous electrical nerve stimulation (TENS) has been reported to effectively alleviate chronic pain, including phantom limb pain (PLP). Recently, literature has focused on modulated TENS patterns, such as pulse width modulation (PWM) and burst modulation (BM), as alternatives to conventional, non-modulated (NM) sensory neurostimulation to increase the efficiency of rehabilitation. However, there is still limited knowledge of how these modulated TENS patterns affect corticospinal (CS) and motor cortex activity. Therefore, our aim was to first investigate the effect of modulated TENS patterns on CS activity and corticomotor map in healthy subjects. Motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) were recorded from three muscles before and after the application of TENS interventions. Four different TENS patterns (PWM, BM, NM 40 Hz, and NM 100 Hz) were applied. The results revealed significant facilitation of CS excitability following the PWM intervention. We also found an increase in the volume of the motor cortical map following the application of the PWM and NM (40 Hz). Although PLP alleviation has been reported to be associated with an enhancement of corticospinal excitability, the efficiency of the PWM intervention to induce pain alleviation should be validated in a future clinical study in amputees with PLP.


Assuntos
Córtex Motor , Estimulação Elétrica Nervosa Transcutânea , Potencial Evocado Motor/fisiologia , Voluntários Saudáveis , Humanos , Córtex Motor/fisiologia , Tratos Piramidais/fisiologia , Estimulação Magnética Transcraniana/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos
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