Journal of neurotrauma
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Journal of neurotrauma · Mar 2019
Clinical TrialSpinal Cord Blood Flow in Patients with Acute Spinal Cord Injuries.
The effect of traumatic spinal cord injury (TSCI) on spinal cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guideline of 85-90 mm Hg improves SCBF is also unclear. Here, we use laser speckle contrast imaging intraoperatively to visualize blood flow at the injury site in 22 patients with acute, severe spinal cord injuries (American Spinal Injuries Association Impairment Scale, grades A-C). ⋯ In 7 of 19 patients with MAP 85-90 mm Hg, parts of the injury site were only perfused in systole, but not in diastole, which we term diastolic ischemia. We conclude that acute, severe TSCI produces three pathological blood flow patterns at the injury site. Intervention to increase blood pressure may elicit potentially detrimental SCBF responses in some patients.
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Journal of neurotrauma · Mar 2019
Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury.
Spinal cord injury (SCI) produces a toxic inflammatory microenvironment that negatively affects plasticity and recovery. Recently, we showed glial activation and peripheral myeloid cell infiltration extending beyond the epicenter through the remote lumbar cord after thoracic SCI. The presence and role of infiltrating monocytes is important, especially in the lumbar cord where locomotor central pattern generators are housed. ⋯ Further, acute rehabilitation exacerbated the inflammatory profile of infiltrated macrophages in the lumbar cord. Such high inflammatory potential and negative response to rehabilitation of infiltrating macrophages within lumbar locomotor central pattern generators likely impedes activity-dependent recovery. Therefore, limiting active trafficking of macrophages into the lumbar cord identifies a novel target for SCI therapies to improve locomotion.
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Journal of neurotrauma · Mar 2019
Meta AnalysisEarly Surgical Decompression Improves Neurological Outcome after Complete Traumatic Cervical Spinal Cord Injury: A Meta-Analysis.
In patients with traumatic spinal cord injury (tSCI) a distinction in surgical urgency is made on the basis of the severity of the initial neurological injury. The optimal timing of surgical decompression, as well as its impact on neurological recovery, is as of yet undetermined. This study addresses neurological improvement after early and late surgery for complete and incomplete cervical tSCI. ⋯ Whereas in patients with incomplete cervical tSCI (n = 636), improvement was similar between early and late surgery (respectively 30.4%, 95% CI: 19.8-41.6% and 32.5%, 95% CI: 21.4-45.8%; OR 0.9 [95% CI: 0.4-1.9]). These data suggest a paradigm shift in the treatment of patients with complete cervical tSCI, as surgical decompression within 24 h is more frequently associated with clinically meaningful improvement. In incomplete cervical tSCI, neurological outcome is similar between early and late surgery.
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Journal of neurotrauma · Mar 2019
Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury.
Spinal cord injury (SCI) induces neuropathic pain that is refractory to treatment. Central and peripheral immune responses to SCI play critical roles in pain development. Although immune responses in the dorsal horn have been implicated in SCI-pain, immune mechanisms in the periphery, especially in the dorsal root ganglia (DRG), where nociceptor cell bodies reside, have not been well studied. ⋯ Our data suggest that macrophage presence in the DRG may be an important effector of pain development, and early wheel walking exercise may mediate pain prevention by modulating the injury-induced macrophage response in the DRG. Further supportive evidence demonstrated that rats that developed pain despite exercise intervention still displayed a significantly elevated number of macrophages in the DRG. Collectively, these data suggest that macrophage presence in the DRG may be an amenable cellular target for future therapies.
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Journal of neurotrauma · Mar 2019
Randomized Controlled Trial Multicenter StudyClinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury.
Human neural stem cell transplantation (HuCNS-SC®) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. ⋯ At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.