scholarly journals Human Deep Cortical Neurons Promote Regeneration and Recovery After Cervical Spinal Cord Injury

2021 ◽  
Author(s):  
Vanessa Madelyn Doulames ◽  
James Weimann ◽  
Giles W Plant

Cervical spinal cord injuries (SCI) sever and permanently disrupt sensorimotor neural circuitry. Restoring connectivity within the damaged circuitry is critical to improving function. Herein we report robust regeneration of severed neural circuitry in a rat SCI model following transplantation of human induced pluripotent cells differentiated towards a deep cortical neuron lineage (iPSC-DCNs). In vivo, iPSC-DCNs: (1) integrated within the damaged cord and extended axons to caudal targets, (2) reversed SCI pathophysiology, (3) promoted robust regeneration of severed host supraspinal neural tracts, (4) and improved sensorimotor function. The results herein represent a significant paradigm shift in anatomical and functional outcomes over current preclinical/clinical models and demonstrates the survival and efficacy of human stem cell-derived cortical neurons in a SCI.

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3214
Author(s):  
Krisztián Pajer ◽  
Tamás Bellák ◽  
Antal Nógrádi

Hundreds of thousands of people suffer spinal cord injuries each year. The experimental application of stem cells following spinal cord injury has opened a new era to promote neuroprotection and neuroregeneration of damaged tissue. Currently, there is great interest in the intravenous administration of the secretome produced by mesenchymal stem cells in acute or subacute spinal cord injuries. However, it is important to highlight that undifferentiated neural stem cells and induced pluripotent stem cells are able to adapt to the damaged environment and produce the so-called lesion-induced secretome. This review article focuses on current research related to the secretome and the lesion-induced secretome and their roles in modulating spinal cord injury symptoms and functional recovery, emphasizing different compositions of the lesion-induced secretome in various models of spinal cord injury.


2006 ◽  
Vol 72 (6) ◽  
pp. 525-529 ◽  
Author(s):  
D.L. Franga ◽  
M.L. Hawkins ◽  
R.S. Medeiros ◽  
D. Adewumi

Cervical spinal cord injury is a highly morbid condition frequently associated with cardiovascular instability. This instability may include bradyarrhythmias, as well as hypotension, and usually resolves in a relatively short time. However, over a 3-year period (January 2003–December, 2005), 5 of 30 patients with complete cervical spinal cord injuries seen at our Level I trauma center required placement of permanent cardiac pacemakers for recurrent bradycardia/asystolic events. Strong consideration for pacemaker placement should be given for those spinal cord-injured patients with symptomatic bradyarrhythmic events still occurring 2 weeks after injury.


2015 ◽  
Vol 44 (4) ◽  
pp. 1285-1298 ◽  
Author(s):  
Tim Bhatnagar ◽  
Jie Liu ◽  
Andrew Yung ◽  
Peter A. Cripton ◽  
Piotr Kozlowski ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arabinda Mishra ◽  
Feng Wang ◽  
Li Min Chen ◽  
John C. Gore

Abstract This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.


2017 ◽  
Vol 43 (4) ◽  
pp. E14 ◽  
Author(s):  
Andrew C. Vivas ◽  
Steven W. Hwang ◽  
Joshua M. Pahys

Phrenic stimulators offer an alternative to standard mechanical ventilation as well as the potential for ventilator independence in select patients with chronic respiratory failure. Young patients (< 10 years old) with high cervical spinal cord injuries often develop paralytic scoliosis due to loss of muscle tone caudal to their spinal cord lesion. Growing rod systems allow for stabilization of spinal deformity while permitting continued growth of the spine and thoracic cavity. Magnetically controlled growing rods (MCGRs) offer the advantage of noninvasive expansion, as opposed to the operative expansion required in traditional growing rod systems. To the authors’ knowledge, this is the first reported case of MCGRs in a patient with a diaphragmatic pacemaker (DP). A 7-year-old boy with ventilator dependence after a high cervical spinal cord injury presented to the authors’ institution with paralytic scoliosis that progressed to > 120°. The patient had previously undergone insertion of phrenic nerve stimulators for diaphragmatic pacing. The decision was made to insert MCGRs bilaterally to stabilize his deformity, because the planned lengthening surgeries that are necessary with traditional growing rods would be poorly tolerated in this patient. The patient’s surgery and postoperative course were uneventful. The DP remained functional after insertion and lengthening of the MCGRs by using the external magnet. The DP had no effect on the expansion capability of the MCGRs. In conclusion, the MCGRs appear to be compatible with the DP. Further studies are needed to validate the long-term safety and compatibility of these 2 devices.


1999 ◽  
Vol 6 (1) ◽  
pp. E6 ◽  
Author(s):  
Fernando L. Vale ◽  
Jennifer Burns ◽  
Amie B. Jackson ◽  
Mark N. Hadley

The optimal management of acute spinal cord injuries remains to be defined. The authors prospectively applied resuscitation principles of volume expansion and blood pressure maintenance to 77 patients who presented with acute neurological deficits as a result of spinal cord injuries occurring from C-1 through T-12 in an effort to maintain spinal cord blood flow and prevent secondary injury. According to the Intensive Care Unit protocol, all patients were managed by Swan-Ganz and arterial blood pressure catheters and were treated with immobilization and fracture reduction as indicated. Intravenous fluids, colloid, and vasopressors were administered as necessary to maintain mean arterial blood pressure above 85 mm Hg. Surgery was performed for decompression and stabilization, and fusion in selected cases. Sixty-four patients have been followed at least 12 months postinjury by means of detailed neurological assessments and functional ability evaluations. Sixty percent of patients with complete cervical spinal cord injuries improved at least one Frankel or American Spinal Injury Association (ASIA) grade at the last follow-up review. Thirty percent regained the ability to walk and 20% had return of bladder function 1 year postinjury. Thirty-three percent of the patients with complete thoracic spinal cord injuries improved at least one Frankel or ASIA grade. Approximately 10% of the patients regained the ability to walk and had return of bladder function. As of the 12-month follow-up review, 92% of patients demonstrated clinical improvement after sustaining incomplete cervical spinal cord injuries compared to their initial neurological status. Ninety-two percent regained the ability to walk and 88% regained bladder function. Eighty-eight percent of patients with incomplete thoracic spinal cord injuries demonstrated significant improvements in neurological function 1 year postinjury. Eighty-eight percent were able to walk and 63% had return of bladder function. The authors conclude that the enhanced neurological outcome that was observed in patients after spinal cord injury in this study was in addition to, and/or distinct from, any potential benefit provided by surgery. Early and aggressive medical management (volume resuscitation and blood pressure augmentation) of patients with acute spinal cord injuries optimizes the potential for neurological recovery after sustaining trauma.


1975 ◽  
Vol 42 (3) ◽  
pp. 330-337 ◽  
Author(s):  
Alain B. Rossier ◽  
Jean Berney ◽  
Arthur E. Rosenbaum ◽  
Jurg Hachen

✓ Gas myelography was carried out in 22 patients with acute cervical spinal cord injuries in whom oily contrast media seemed contraindicated. The authors believe this technique makes a valuable contribution to the basic decision regarding the surgical versus medical treatment of a specific patient with a cervical cord injury. They emphasize the importance of visualizing cord compression due to disc herniation in these cases and conclude that gases are the optimal contrast agents for visualization of the entire circumference of the spinal cord.


2011 ◽  
Vol 77 (4) ◽  
pp. 426-429
Author(s):  
Thomas Butler ◽  
Susanna Shin ◽  
Jay Collins ◽  
Rebecca C. Britt ◽  
Scott F. Reed ◽  
...  

Body surfing accidents (BSA) can cause cervical spinal cord injuries (CSCIs) that are associated with near-drowning (ND). The submersion injury from a ND can result in aspiration and predispose to pulmonary complications. We predicted a worse outcome (particularly the development of pneumonia) in patients with CSCIs associated with ND. A retrospective review was performed of patients who were treated at Eastern Virginia Medical School for a CSCI resulting from a blunt mechanism. Data collected included basic demographic data, data regarding injury and in-hospital outcomes, and discharge data, including discharge disposition. Statistics were performed using χ2 and Student t test. In 2003 to 2008, 141 patients were treated for CSCIs with inclusion criteria. Thirty patients (21%) had an associated ND (BSA) and 111 patients (79%) did not (BLT). The cohorts were similar in mean age (BSA, 45 years; BLT, 50 years; P = 0.16) and male gender distribution (BSA, 93%; BLT, 79%; P = 0.13). The cohorts were similar in injury severity using Injury Severity Score (BSA, 22; BLT, 24; P = 0.65). The cohorts were similar in rates of developing pneumonia (BSA, 3%; BLT, 12%; P = 0.31). The rate of infection was significantly higher in the cohort without an associated near-drowning (BSA, 10%; BLT, 32%; P = 0.033). The mean intensive care unit stay (BSA, 3.5 days; BLT, 11.3 days; P = 0.057) and the rate of mortality were similar (BSA, 10%; BLT, 10% P = 0.99). Those patients with an associated ND had a shorter hospital stay (BSA, 5.7 days; BLT, 22.2 days; P = 0.007) and a better chance of being discharged home (BSA, 57%; BLT, 27%; P = 0.004). CSCIs after a BSA do better than their counterparts without an associated ND. CSCIs associated with ND appear to be isolated injuries with minimal pulmonary involvement despite submersion injuries.


2016 ◽  
Vol 2016 ◽  
pp. 1-15
Author(s):  
Anne Kastner ◽  
Valéry Matarazzo

High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth.


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