Treatment With the Neutralizing Antibody Against Repulsive Guidance Molecule-a Promotes Recovery From Impaired Manual Dexterity in a Primate Model of Spinal Cord Injury

Nakagawa, Hiroe; Ninomiya, Taihei; Yamashita, Toshio

doi:10.1093/cercor/bhx338

Cited by 46 publications

(39 citation statements)

References 55 publications

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“…We used an anti-human RGMa antibody that was raised against the C-terminal sequence of human RGMa 21,35 . Neutralization of RGMa by delivery of C-terminal antibodies has been demonstrated to promote axonal growth in models of spinal cord trauma in rats 21,35 and monkeys 39 .…”

Section: Discussionmentioning

confidence: 99%

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

Nevoux

Alexandru

Bellocq

et al. 2021

Sci Rep

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Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

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Section: Discussionmentioning

confidence: 99%

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

Nevoux

Alexandru

Bellocq

et al. 2021

Sci Rep

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“…It was reported to express in the glial scar and myelin and is accumulated in lesioned sites after a traumatic injury of the spinal cord and brains in rodents [10]. In addition to rodents, administration of neutralizing antibody against RGMA was found to lead to recovery from impaired manual dexterity in a monkey model of SCI [12]. On this basis, we further modified RGMA expression in the SCI rat models.…”

Section: Discussionmentioning

confidence: 98%

“…RGMA is a GPI-linked glycoprotein that exists in soluble and membrane-bound forms and suppresses neurite growth by binding to neogenin, its neuronal receptor [10]. Correspondingly, inhibition of either RGMA or neogenin was found to promote neuronal survival and functional recovery after SCI [11,12]. The signal transducer and activator of transcription 3 (STAT3) signaling is implicated in multiple inflammatory responses by regulating some proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17, and its downregulation was found to reduce spinal cord neuroinflammation and promote neuronal functional recovery after SCI [13,14].…”

Section: Introductionmentioning

confidence: 99%

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Yang

Sun

2020

J Orthop Surg Res

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Background The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism. Methods A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis. Results miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3. Conclusion This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.

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“…On the contrary, CT/MRI fusion has been validated for the postoperative assessment of electrodes in many studies [38][39][40]. In gamma knife radiosurgery, Nakagawa et al [41] showed more distortion with stereotactic MRI than with a 3-T image co-registered to a stereotactic CT. Thus, whatever preoperative imaging system is chosen, a postoperative MRI is the only way to validate the process.…”

Section: Co-registration Computed Tomography and Mrimentioning

confidence: 99%

Comparison between 1.5- and 3-T Magnetic Resonance Acquisitions for Direct Targeting Stereotactic Procedures for Deep Brain Stimulation: A Phantom Study

Poulen¹,

Seng²,

Champfleur³

et al. 2020

Stereotact Funct Neurosurg

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Introduction: Deep brain stimulation (DBS) is a well-established treatment for movement disorders. High magnetic fields could have an impact on distortion. We evaluated 1.5and 3-T magnetic resonance imaging (MRI) sequences for accuracy, precision, and trueness of our MRI-guided direct targeting protocol. Methods: Effects of distortion on MR sequences (T1-and T2-weighted sequences) can be evaluated using a dedicated phantom (Elekta). Field strength capabilities were assessed on Siemens Avanto (1.5 T) and Skyra (3 T) scanners. We assessed the precision of our stereotactic MRIguided procedure. Results: We focused on the risk of error due to a high field strength. Error values on the localizer box were between 0.4 and 0.7 mm at 1.5 T and between 0.6 and 2 mm at 3 T. The most accurate 1.5-T sequence is the 3D FLASH T1-weighted sequence, which had an accuracy value of 0.6 mm. At 3 T, the accuracy value of the isotropic 3D FLASH T1-weighted sequence was 1.6 mm. Conclusion: Given the millimetric size of stereotactic targets and electrodes, lead implantation for neuromodulation therapy needs to be accurate. We demonstrate that 3-T imaging could not be used for stereotaxy in our MRI-guided direct targeting protocol because of a risk of error induced by distortion.

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Treatment With the Neutralizing Antibody Against Repulsive Guidance Molecule-a Promotes Recovery From Impaired Manual Dexterity in a Primate Model of Spinal Cord Injury

Cited by 46 publications

References 55 publications

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Comparison between 1.5- and 3-T Magnetic Resonance Acquisitions for Direct Targeting Stereotactic Procedures for Deep Brain Stimulation: A Phantom Study

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