Nimodipine Promotes Functional Recovery After Spinal Cord Injury in Rats

Spinal cord injury (SCI) is a devastating condition that results in severe motor, sensory, and autonomic dysfunction. The L-/T-type calcium channel blocker nimodipine (NMD) exerts a protective effect on neuronal injury; however, the protective effects of long-term administration of NMD in subjects with SCI remain unknown. Thus, the aim of this study was to evaluate the role of long-term treatment with NMD on a clinically relevant SCI model. Female rats with SCI induced by 25 mm contusion were subcutaneously injected with vehicle or 10 mg/kg NMD daily for six consecutive weeks. We monitored the motor score, hind limb grip strength, pain-related behaviors, and bladder function in this study to assess the efficacy of NMD in rats with SCI. Rats treated with NMD showed improvements in locomotion, pain-related behaviors, and spasticity-like symptoms, but not in open-field spontaneous activity, hind limb grip strength or bladder function. SCI lesion areas and perilesional neuronal numbers, gliosis and calcitonin gene-related peptide (CGRP+) fiber sprouting in the lumbar spinal cord and the expression of K+–Cl− cotransporter 2 (KCC2) on lumbar motor neurons were also observed to further explore the possible protective mechanisms of NMD. NMD-treated rats showed greater tissue preservation with reduced lesion areas and increased perilesional neuronal sparing. NMD-treated rats also showed improvements in gliosis, CGRP+ fiber sprouting in the lumbar spinal cord, and KCC2 expression in lumbar motor neurons. Together, these results indicate that long-term treatment with NMD improves functional recovery after SCI, which may provide a potential therapeutic strategy for the treatment of SCI.

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Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection

Neurorehabilitation and Neural Repair ◽

10.1177/1545968319829456 ◽

2019 ◽

Vol 33 (3) ◽

pp. 225-231 ◽

Cited By ~ 3

Author(s):

Kazu Kobayakawa ◽

Kyleigh Alexis DePetro ◽

Hui Zhong ◽

Bau Pham ◽

Masamitsu Hara ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Ventral Horn ◽

Lumbar Spinal Cord ◽

Locomotor Training ◽

Synaptic Structure ◽

Cord Injury ◽

Lumbar Spinal ◽

Spinal Cord Hemisection ◽

Activity Dependent

Background. We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. Methods. In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. Results. Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. Conclusions. Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.

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Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

Neural Plasticity ◽

10.1155/2017/7351238 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Yu-Ting Zhang ◽

Hui Jin ◽

Jun-Hua Wang ◽

Lan-Yu Wen ◽

Yang Yang ◽

...

Keyword(s):

Spinal Cord ◽

Electrical Stimulation ◽

Muscle Atrophy ◽

Motor Neurons ◽

Lumbar Spinal Cord ◽

Hindlimb Muscle ◽

Neurotrophin 3 ◽

Spinal Cord Segment ◽

Cord Injury ◽

Lumbar Spinal

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.

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Effects of chronic spinal cord injury on relationships among ion channel and receptor mRNAs in mouse lumbar spinal cord

10.1101/357665 ◽

2018 ◽

Cited By ~ 1

Author(s):

Virginia B. Garcia ◽

Matthew D. Abbinanti ◽

Ronald M. Harris-Warrick ◽

David J. Schulz

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Ion Channel ◽

Motor Neurons ◽

Receptor Expression ◽

Lumbar Spinal Cord ◽

Mrna Levels ◽

Absolute Quantitation ◽

Cord Injury ◽

Lumbar Spinal

ABSTRACTSpinal cord injury (SCI) causes widespread changes in gene expression of the spinal cord, even in the undamaged spinal cord below the level of the lesion. Less is known about changes in the correlated expression of genes after SCI. We investigated gene co-expression networks among voltage-gated ion channel and neurotransmitter receptor mRNA levels using quantitative RT-PCR in longitudinal slices of the mouse lumbar spinal cord in control and chronic SCI animals. These longitudinal slices were made from the ventral surface of the cord, thus forming slices relatively enriched in motor neurons or interneurons. We performed absolute quantitation of mRNA copy number for 50 ion channel or receptor transcripts from each sample, and used multiple correlation analyses to detect patterns in correlated mRNA levels across all pairs of genes. The majority of channels and receptors changed in expression as a result of chronic SCI, but did so differently across slice levels. Furthermore, motor neuron enriched slices experienced an overall loss of correlated channel and receptor expression, while interneuron slices showed a dramatic increase in the number of positively correlated transcripts. These correlation profiles suggest that spinal cord injury induces distinct changes across cell types in the organization of gene co-expression networks for ion channels and transmitter receptors.

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Pathophysiology of Autonomic Dysreflexia: Long-Term Treatment With Terazosin in Adult and Paediatric Spinal Cord Injury Patients Manifesting Recurrent Dysreflexic Episodes

The Journal of Urology ◽

10.1097/00005392-199909010-00120 ◽

1999 ◽

Vol 162 (3 Part 1) ◽

pp. 968-969 ◽

Cited By ~ 1

Author(s):

S. Vaidyanathan ◽

B.M. Soni ◽

P. Sett ◽

J.W.H. Watt ◽

T. Oo ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Term Treatment ◽

Autonomic Dysreflexia ◽

Long Term Treatment ◽

Cord Injury

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Patients’ perspective of botulinum toxin-A as a long-term treatment option for neurogenic detrusor overactivity secondary to spinal cord injury

BJU International ◽

10.1111/j.1464-410x.2009.08368.x ◽

2009 ◽

Vol 104 (2) ◽

pp. 216-220 ◽

Cited By ~ 16

Author(s):

Satoshi Hori ◽

Prasad Patki ◽

Kaka H. Attar ◽

Soran Ismail ◽

Joana C. Vasconcelos ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Botulinum Toxin ◽

Botulinum Toxin A ◽

Term Treatment ◽

Neurogenic Detrusor Overactivity ◽

Long Term Treatment ◽

Cord Injury ◽

Patients Perspective

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Unlike Brief Inhibition of Microglia Proliferation after Spinal Cord Injury, Long-Term Treatment Does Not Improve Motor Recovery

Brain Sciences ◽

10.3390/brainsci11121643 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1643

Author(s):

Gaëtan Poulen ◽

Sylvain Bartolami ◽

Harun N. Noristani ◽

Florence E. Perrin ◽

Yannick N. Gerber

Keyword(s):

Spinal Cord ◽

Ex Vivo ◽

Spinal Injury ◽

Oral Treatment ◽

Term Treatment ◽

Motor Recovery ◽

Beneficial Effects ◽

Long Term Treatment ◽

Cord Injury

Microglia are major players in scar formation after an injury to the spinal cord. Microglia proliferation, differentiation, and survival are regulated by the colony-stimulating factor 1 (CSF1). Complete microglia elimination using CSF1 receptor (CSF1R) inhibitors worsens motor function recovery after spinal injury (SCI). Conversely, a 1-week oral treatment with GW2580, a CSF1R inhibitor that only inhibits microglia proliferation, promotes motor recovery. Here, we investigate whether prolonged GW2580 treatment further increases beneficial effects on locomotion after SCI. We thus assessed the effect of a 6-week GW2580 oral treatment after lateral hemisection of the spinal cord on functional recovery and its outcome on tissue and cellular responses in adult mice. Long-term depletion of microglia proliferation after SCI failed to improve motor recovery and had no effect on tissue reorganization, as revealed by ex vivo diffusion-weighted magnetic resonance imaging. Six weeks after SCI, GW2580 treatment decreased microglial reactivity and increased astrocytic reactivity. We thus demonstrate that increasing the duration of GW2580 treatment is not beneficial for motor recovery after SCI.

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