Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa

2010 ◽  
Vol 12 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Masanori Aoki ◽  
Haruhiko Kishima ◽  
Kazuhiro Yoshimura ◽  
Masahiro Ishihara ◽  
Masaki Ueno ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lamina Propria ◽  
Motor Function ◽  
Functional Recovery ◽  
Olfactory Mucosa ◽  
Respiratory Mucosa ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Object The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. Methods Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa–transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. Conclusions Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

scholarly journals Restoring Function After Severe Spinal Cord Injury Through Bioluminescence-Driven Optogenetics

2019 ◽  
Author(s):  
Eric D. Petersen ◽  
Erik D. Sharkey ◽  
Akash Pal ◽  
Lateef O. Shafau ◽  
Jessica R. Zenchak ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neuron ◽  
Functional Recovery ◽  
Rational Approach ◽  
Lumbar Spinal Cord ◽  
Locomotor Recovery ◽  
Non Invasive ◽  
Cord Injury ◽  
Neuronal Connections

The ability to manipulate specific neuronal populations of the spinal cord following spinal cord injury (SCI) could prove highly beneficial for rehabilitation in patients through maintaining and strengthening still existing neuronal connections and/or facilitating the formation of new connections. A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics (BL-OG), where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ). This approach utilizes ion channels for current conduction while activating the channels through application of a small chemical compound, thus allowing non-invasive stimulation and recruitment of all targeted neurons. Rats were transduced in the lumbar spinal cord with AAV2/9 to express the excitatory LMO3 under control of a pan-neuronal or motor neuron-specific promoter. A day after contusion injury of the thoracic spine, rats received either CTZ or vehicle every other day for 2 weeks. Activation of either interneuron or motor neuron populations below the level of injury significantly improved locomotor recovery lasting beyond the time of stimulation. Utilizing histological and gene expression methods we identified neuronal plasticity as a likely mechanism underlying the functional recovery. These findings provide a foundation for a rational approach to spinal cord injury rehabilitation, thereby advancing approaches for functional recovery after SCI.

scholarly journals Recovery of paralyzed limb motor function in canine with complete spinal cord injury following implantation of MSC-derived neural network tissue

Biomaterials ◽  
2018 ◽  
Vol 181 ◽  
pp. 15-34 ◽  
Author(s):  
Guo-Hui Wu ◽  
Hui-Juan Shi ◽  
Ming-Tian Che ◽  
Meng-Yao Huang ◽  
Qing-Shuai Wei ◽  
...  
Keyword(s):  
Neural Network ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Co-transplantation of autologous OM-MSCs and OM-OECs: a novel approach for spinal cord injury

2016 ◽  
Vol 27 (3) ◽  
pp. 259-270 ◽  
Author(s):  
Lite Ge ◽  
Kai Liu ◽  
Zhonghua Liu ◽  
Ming Lu
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Olfactory Mucosa ◽  
Olfactory Ensheathing Cells ◽  
Novel Approach ◽  
Cord Injury ◽  
High Proliferation Rate ◽  
Combined Strategy

AbstractSpinal cord injury (SCI) is a disastrous injury that leads to motor and sensory dysfunctions in patients. In recent years, co-transplantation has become an increasingly used therapeutic treatment for patients with SCI. Both mesenchymal stem cells (MSCs) and olfactory-ensheathing cells (OECs) have been adopted to ameliorate SCI, with promising outcomes. Remarkable effects on the rehabilitation of patients with SCI have been achieved using MSCs. Olfactory mucosa (OM) MSCs from human OM are one of the most ideal cell resources for auto-transplantation in clinical application owing to their a high proliferation rate and multipotent capability. In addition, OECs derived from OM have been used to improve functional recovery of SCI and resulted in promising functional recovery in years. Accordingly, co-transplantation of OM-MSCs coupled with OM-OECs has been adopted to improve the recovery of SCI. Here we reviewed the reported applications of OM-MSCs and OM-OECs for SCI treatment and proposed that a novel combined strategy using both autologous OM-MSCs and OM-OECs would achieve a better approach for the treatment of SCI.

scholarly journals Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Aynur DEMIREL ◽  
Jia LI ◽  
Casey MORROW ◽  
Stephen BARNES ◽  
Jan JANSEN ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Total Energy ◽  
Acute Care ◽  
Ketogenic Diet ◽  
Motor Function ◽  
Functional Recovery ◽  
Functional Independence ◽  
Neurological Recovery ◽  
Cord Injury

Abstract Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a rat model of SCI, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD, started during acute care, improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of our proposed study are to 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory function, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study design, 60 participants with acute SCI will be randomly assigned to KD or SD in a 1:1 ratio. We intend to recruit 24 participants for each group with traumatic SCI (C5–T12, American Spinal Injury Association impairment scale A–C, and aged 18–60 years). Patients will be taken to acute care after their injury. Neurological and functional examinations, resting energy expenditure, blood, urine, stool collection and protein analyses related to neuro recovery will be done within 72 h of injury, as baseline measures. Patients received five weeks of KD or SD according to their allocation. The KD is a high-fat, low-carbohydrate diet (3:1 ratio of fat: carbohydrate + protein) that includes ~75% total energy as fat, ~20% as protein, and ~5% as carbohydrate and fiber. The SD includes ~45-50% total energy as carbohydrate and fiber, ~30% total energy as fat, and ~20% total energy as protein. All baseline examinations will be repeated at discharge from the hospital at week 5 (discharge measure). Discussion: The proposed diet intervention is practical and safe and is expected to translate into efficacious early nutritional interventions. Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries such as traumatic brain injury and stroke.

scholarly journals Ultrasound stimulation improves inflammatory resolution, neuroprotection, and functional recovery after spinal cord injury

2021 ◽  
Author(s):  
Yu-ri Hong ◽  
Eun-hee Lee ◽  
Ki-su Park ◽  
Mun Han ◽  
Kyoung-Tae Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Motor Function ◽  
Functional Recovery ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Injury Site ◽  
Cord Injury ◽  
Anti Inflammatory

Abstract Spinal cord injury (SCI) is associated with limited functional recovery. Despite advances in neuroscience, realistic therapeutic treatments for SCI remain unavailable. In this study, the effects of non-invasive ultrasound (US) treatment on behavior and inflammatory responses were evaluated in a rat model of SCI. Adult female Sprague–Dawley rats were subjected to spinal cord contusion injury. Two different US parameters (SCIU5: 5% and SCIU40: 40% duty cycle) were applied, and their effects on behavioral recovery after SCI were quantified. Tissue and neuronal responses were detected. Immunofluorescence was used to detect inflammatory markers. In the rat model of SCI, motor function was more effectively restored, and the lesion cavity area was smaller in the SCIU5 group. Furthermore, the SCIU5 protocol elicited an anti-inflammatory response at the injury site by reducing degenerative FJC-labeled neurons, macrophage/microglia activation, and infiltration. Thus, the lesion area decreased, and tissue density increased. Meanwhile, the SCIU40 protocol did not improve motor function or induce an anti-inflammatory response at the injury site. The SCIU5 protocol effectively accelerated the rate of improved exercise performance in the rat model while reducing inflammation. Accordingly, appropriate US stimulation may represent a promising treatment modality for SCI with beneficial anti-inflammatory effects.

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