Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

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Safety and Feasibility of Autologous Olfactory Ensheathing Cell and Bone Marrow Mesenchymal Stem Cell Co-transplantation in Chronic Human Spinal Cord Injury: A Clinical Trial

10.21203/rs.3.rs-435425/v1 ◽

2021 ◽

Author(s):

Homa Zamani ◽

Mina Soufizomorrod ◽

Saeed Oraee-Yazdani ◽

Dariush Naviafar ◽

Mohammadhosein Akhlaghpasand ◽

...

Keyword(s):

Spinal Cord ◽

Bone Marrow ◽

Spinal Cord Injury ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Safety Issue ◽

Functional Evaluation ◽

Olfactory Ensheathing Cell ◽

Human Spinal Cord ◽

Cord Injury

Abstract Cell-based therapies are considered as promising strategies for spinal cord regeneration. However, a combinatorial cell therapeutic approach seems more beneficial as it can target various aspects of the injury. Here, we assessed the safety and feasibility of autologous mucosal Olfactory Ensheathing Cell (OEC) and bone marrow Mesenchymal Stem Cell (MSC) co-transplantation in patients with chronic, complete (American Spinal Injury Association (ASIA) classification A) Spinal Cord Injury (SCI). Three patients with the traumatic SCI of the thoracic level were enrolled. They received autologous OEC and MSC combination through the lumbar puncture. All adverse events and possible functional outcomes were documented performing pre- and post-operative general clinical examination, Magnetic Resonance Imaging (MRI), neurological assessment based on the International Standard of Neurological Classification for SCI (ISNCSCI), and functional evaluation using Spinal Cord Independence Measure version III (SCIM III). No serious safety issue was recorded during the two years of follow-up. MRI findings remained unchanged with no neoplastic tissue formation. ASIA impairment scale improved from A to B in one of the participants. SCIM III evaluation also showed some degrees of progress in this patient's quality of life. The two other patients had negligible or no improvement in their sensory scores without any changes in the ASIA impairment scale and SCIM III scores. No motor recovery was observed in any of the participants. Overall, this two-year trial was not associated with any adverse findings, which may suggest the safety of autologous OEC and bone marrow MSC combination for the treatment of human SCI.This study was registered at the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20160110025930N2/ registration date: 2018-09-29).

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Motoneuron Death after Human Spinal Cord Injury

Journal of Neurotrauma ◽

10.1089/neu.2015.4374 ◽

2017 ◽

Vol 34 (3) ◽

pp. 581-590 ◽

Cited By ~ 16

Author(s):

Robert M. Grumbles ◽

Christine K. Thomas

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Human Spinal Cord ◽

Cord Injury

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Disordered control of the urinary bladder after human spinal cord injury: what are the problems?

Autonomic Dysfunction After Spinal Cord Injury - Progress in Brain Research ◽

10.1016/s0079-6123(05)52004-1 ◽

2006 ◽

pp. 51-57 ◽

Cited By ~ 18

Author(s):

Patrick J. Potter

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Urinary Bladder ◽

Human Spinal Cord ◽

Cord Injury

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Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0050 ◽

2017 ◽

Vol 28 (1) ◽

pp. 15-20 ◽

Cited By ~ 9

Author(s):

Dauda Abdullahi ◽

Azlina Ahmad Annuar ◽

Masro Mohamad ◽

Izzuddin Aziz ◽

Junedah Sanusi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cord Compression ◽

Acute Injury ◽

Optimal Timing ◽

Spinal Cord Trauma ◽

Rat Models ◽

Human Spinal Cord ◽

Cord Injury ◽

Transient Force

AbstractIt has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

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