Local injection of BDNF producing mesenchymal stem cells increases neuronal survival and synaptic stability following ventral root avulsion

Increased abdominal muscle wall activity may be part of a visceromotor reflex (VMR) response to noxious stimulation of the bladder. However, information is sparse regarding the effects of cauda equina injuries on the VMR in experimental models. We studied the effects of a unilateral L6-S1 ventral root avulsion (VRA) injury and acute ventral root reimplantation (VRI) into the spinal cord on micturition reflexes and electromyographic activity of the abdominal wall in rats. Cystometrogram (CMG) and electromyography (EMG) of the abdominal external oblique muscle (EOM) were performed. All rats demonstrated EMG activity of the EOM associated with reflex bladder contractions. At 1 wk after VRA and VRI, the duration of the EOM EMG activity associated with reflex voiding was significantly prolonged compared with age-matched sham rats. However, at 3 wk postoperatively, the duration of the EOM responses remained increased in the VRA series but had normalized in the VRI group. The EOM EMG duration was normalized for both VRA and VRI groups at 8–12 wk postoperatively. CMG recordings show increased contraction duration at 1 and 3 wk postoperatively for the VRA series, whereas the contraction duration was only increased at 1 wk postoperatively for the VRI series. Our studies suggest that a unilateral lumbosacral VRA injury results in a prolonged VMR to bladder filling using a physiological saline solution. An acute root replantation decreased the VMR induced by VRA injury and provides earlier sensory recovery.

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Mesenchymal Stem Cells and NF-κB Sensing Interleukin-4 Over-Expressing Mesenchymal Stem Cells Are Equally Effective in Mitigating Particle-Associated Chronic Inflammatory Bone Loss in Mice

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.757830 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ning Zhang ◽

Takeshi Utsunomiya ◽

Tzuhua Lin ◽

Yusuke Kohno ◽

Masaya Ueno ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Loss ◽

Chronic Inflammation ◽

Local Injection ◽

Interleukin 4 ◽

M2 Macrophage ◽

Mineral Density ◽

Primary Surgery ◽

Polyethylene Particle

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

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Serotonergic 5-HT1A receptor agonist (8-OH-DPAT) ameliorates impaired micturition reflexes in a chronic ventral root avulsion model of incomplete cauda equina/conus medullaris injury

Experimental Neurology ◽

10.1016/j.expneurol.2012.10.015 ◽

2013 ◽

Vol 239 ◽

pp. 210-217 ◽

Cited By ~ 15

Author(s):

Huiyi H. Chang ◽

Leif A. Havton

Keyword(s):

Receptor Agonist ◽

Cauda Equina ◽

Conus Medullaris ◽

Ventral Root ◽

Root Avulsion ◽

Ventral Root Avulsion ◽

Micturition Reflexes

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Combining timed GDNF and ChABC gene therapy to promote long‐distance regeneration following ventral root avulsion and repair

The FASEB Journal ◽

10.1096/fj.202000559r ◽

2020 ◽

Vol 34 (8) ◽

pp. 10605-10622 ◽

Cited By ~ 1

Author(s):

Ruben Eggers ◽

Fred Winter ◽

Lotte Smit ◽

Maruelle Luimens ◽

Elizabeth M. Muir ◽

...

Keyword(s):

Gene Therapy ◽

Ventral Root ◽

Root Avulsion ◽

Long Distance ◽

Ventral Root Avulsion

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EMG characteristics of the external anal sphincter guarding reflex and effects of a unilateral ventral root avulsion injury in rhesus macaques (Macaca mulatta)

Journal of Neurophysiology ◽

10.1152/jn.00435.2017 ◽

2018 ◽

Vol 120 (6) ◽

pp. 2710-2718

Author(s):

Huiyi H. Chang ◽

Una Lee ◽

Timothy Vu ◽

Victor Pikov ◽

Jaime H. Nieto ◽

...

Keyword(s):

Anal Sphincter ◽

External Anal Sphincter ◽

Rhesus Macaques ◽

Area Under The Curve ◽

Mean Amplitude ◽

Ventral Root ◽

Root Avulsion ◽

Time Frequency ◽

Injury Group ◽

Ventral Root Avulsion

The external anal sphincter (EAS) is important for the maintenance of bowel continence and may be compromised by a variety of neuropathic conditions. However, large animal models for the study of EAS functions have been sparse. The EAS guarding reflex was examined by electromyography (EMG) in neurologically intact rhesus macaques ( n = 6) and at 4–6 wk after a unilateral EAS denervation from an L6–S3 ventral root avulsion (VRA) injury ( n = 6). Baseline EAS EMG recordings were quiescent in all subjects, and evoked responses showed an initial large-amplitude EMG activity, which gradually returned to baseline within 1–2 min. At 4–6 wk postoperatively, the EAS guarding reflex showed a significantly reduced EMG response duration of 47 ± 15 s and area under the curve (AUC) of 0.198 ± 0.097 mV·s compared with the corresponding evoked EAS EMG duration of 102 ± 19 s and AUC of 0.803 ± 0.225 mV·s ( P < 0.05) in the control group. Detailed time- and frequency-domain analysis of the evoked EAS EMG responses for the first 40 s showed no difference between groups for the maximum amplitude but a significant decrease for the mean amplitude across the study period and an early AUC reduction for the first 10 s in the VRA injury group. Time-frequency analysis and power spectrum plots indicated decreased intensity and a narrower midrange of frequencies in the VRA injury group. We conclude that the EAS guarding reflex in rhesus macaques shows characteristic EMG features in control subjects and signs of partial target denervation after a unilateral L6–S3 VRA injury. NEW & NOTEWORTHY The external anal sphincter guarding reflex showed initial large-amplitude peaks and a gradual return to a quiescent baseline after a rectal probe stimulus in rhesus macaques. At 4–6 wk after a unilateral ventral root avulsion (VRA) injury, the electromyography duration, mean amplitude, and area under the curve measurements were decreased. Time-frequency analysis and power spectrum plots indicated decreased intensity and a narrowed midrange of frequencies in the VRA injury cohort.

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