Epidemiology, Physiopathology, and Experimental Therapeutics of Acute Spinal Cord Injury

doi:10.1016/S0749-0704(18)30531-1

Critical Care Clinics

Volume 3, Issue 3, July 1987, Pages 441-452

https://doi.org/10.1016/S0749-0704(18)30531-1 Get rights and content

This article analyzes the epidemiological factors relating to acute spinal cord injury. It also delineates the anatomical and rheologicai characteristics of the spinal cord and denotes the latest concepts in autoregulaticn of spinal cord blood flow. The physiopathology of spinal cord injury is examined in terms of existing animal models, responses of the white and grey matter, and biochemical and biome-chanical correlates. Experimental and clinical therapeutic modalities ranging from hypothermia to opioid antagonists, and adrenergic blockers to free radical scavengers are evaluated.

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Cited by (26)

Systemic Administration of Allogeneic Cord Blood Mononuclear Cells in Adults with Severe Acute Contusion Spinal Cord Injury: Phase 1/2a Pilot Clinical Study–Safety and Primary Efficacy Evaluation
2022, World Neurosurgery
Citation Excerpt :
However, surgical decompression and stabilization is a palliative rather than a pathogenetic treatment and is focused on the spine and not on the spinal cord.14,15 Surgery creates conditions for spinal cord self-recovery.16,17 It has also been shown in numerous studies that SCI treatment outcomes are better in patients who have undergone early surgery.13-15
Phase 1 of the SUBSCI I/IIa (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury) study focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit. The primary end point was safety. The secondary end point was the restoration of motor and sensory function in lower limbs within a 1-year period.
Ten patients with acute contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit were enrolled into phase 1. Patients were treated with 4 infusions of group-matched and rhesus-matched cord blood samples after primary surgery within 3 days after SCI. All patients were followed up for 12 months after SCI. Safety was assessed using adverse events classification depending on severity and relation to cell therapy. Primary efficacy was assessed using dynamics of deficit (ASIA scale).
The overall number of adverse events reached 419 in 10 patients. Only 2 were estimated as possibly related to cell therapy, and the remaining 417 were definitely unrelated. Both adverse events were mild and clinically insignificant. No signs of immunization were found in participants. Analysis of clinical outcomes also showed that cell therapy promotes significant functional restoration of motor function.
The data obtained suggest that systemic administration of allogeneic, non–human leukocyte antigen–matched human umbilical cord blood is safe and shows primary efficacy in adults with severe acute contusion SCI and ASIA level A/B deficit.
Searching for differentially expressed proteins in spinal cord injury based on the proteomics analysis
2020, Life Sciences
Citation Excerpt :
It is noted that severe spinal cord injury will lead to axonal loss, neuronal death, demyelination, neuronal connection disruption between brain and periphery, ultimately resulting in devastating loss of function [15,16]. Clinically, spinal cord injury is a disease with mortality occurring in patients prior to any primary hospital care, while patients treated at the hospital are also prone to mortality [17]. Recently, the potential pathology mechanism of spinal cord injury remains unclear.
We aimed to identify potential differentially expressed proteins that play roles in the spinal cord injury.
The mouse model of spinal cord injury was firstly built, followed by grip strength evaluation. Then, isobaric tags for relative and absolute quantization (iTRAQ) analysis was used to identify differentially expressed proteins at 1, 2, 3 and 8 weeks after spinal cord injury. Finally, analysis of spinal cord injury repair related differentially expressed proteins in the early and middle-late stage of injury was performed followed by the functional analysis.
The result of grip strength evaluation showed that the motor function of the forelimbs of the mouse was significantly impaired after spinal cord injury. In the iTRAQ analysis, a total of 29 common differentially expressed proteins (such as Hbb-bs, Hba, S100a6, Ca1, Apoa4, Hspb1, Hist1h1c, Hist1h1e, Hbb-b1, Apoa1 and S100a10) were obtained at 1, 2, 3 and 8 weeks after spinal cord injury. A total of 70 and 180 common differentially expressed proteins were identified in the early and middle-late stage of injury, respectively. PPAR signaling pathway (involved Apoa1) and VEGF signaling pathway (involved Hspb1) were identified in the middle-late stage of spinal cord injury repair.
Identified differentially expressed proteins and related signaling pathways may be associated with spinal cord injury.
Regional deep hypothermia of the spinal cord protects against ischemic injury during thoracic aortic cross-clamping
1994, The Annals of Thoracic Surgery
We tested in pigs the hypothesis that regional deep hypothermia of the spinal cord achieved by cerebrospinal fluid cooling will protect against ischemic injury during thoracic aortic cross-clamping. Eight control animals underwent aortic cross-clamping at the distal aortic arch and just above the diaphragm for 30 minutes. Eight experimental animals had placement of two subarachnoid perfusion catheters through laminectomies at T4 and the lower lumbar region. The subarachnoid space was perfused with normal saline solution at 6 °C delivered by gravity infusion, with infusion rates adjusted to maintain cord temperatures at less than 20 °C. After 30 minutes of aortic cross-clamping, the infusion was stopped and the cord allowed to warm to body temperature. Hind limb neurologic function was graded by Tarlov's scale. All of the animals in the control group had complete hind limb paraplegia (Tarlov grade 0) postoperatively. Seven of the 8 animals in the experimental group had preservation of hind limb motor function (Tarlov grade 2), and 1 animal had complete hind limb paraplegia (Tarlov grade 0) (p = 0.002, Fisher's exact test). We conclude that regional deep hypothermia of the spinal cord in pigs does provide some protection from ischemic injury during thoracic aortic cross-clamping. Clinically this may be a useful adjunct for prevention of paraplegia during thoracic aortic operations.
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Acute myelopathies (acute transverse myelopathies) can be divided into two major groups. Vascular myelopathies are caused by aortic disease, surgery, or intrinsic vascular disease of cord vessels. Inflammatory/demyelinative myelopathies include lupus erythematosus, various viral infections, and primary demyelinating disease. Criteria for diagnostic decisions and recent data from magnetic resonance imaging are reviewed.
Injection of Mononuclear Stem Cells from Human Umbilical Cord and Placenta into Mice after 3 and 6 weeks of Experimental Spinal Cord Lesion
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