S1P/S1PR3 signaling mediated proliferation of pericytes via Ras/pERK pathway and CAY10444 had beneficial effects on spinal cord injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

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When a romantic partner has a spinal cord injury: Caregiving tasks and resilience as moderators of support quality on psychosocial distress and relational closeness

Journal of Social and Personal Relationships ◽

10.1177/0265407520929761 ◽

2020 ◽

Vol 37 (8-9) ◽

pp. 2551-2577

Author(s):

Andrew M. Ledbetter ◽

Kristen Carr ◽

Gentry Lynn

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Romantic Relationship ◽

Well Being ◽

Psychosocial Distress ◽

Support Providers ◽

Beneficial Effects ◽

Relationship Closeness ◽

Cord Injury ◽

Relational Closeness

Using a sample of 312 people in a romantic relationship with a partner who has a spinal cord injury (SCI), this study examined the separate and combined effects of caregiving tasks, resilience, and received support on the participant’s level of psychosocial distress. We also tested whether such distress might mediate the effect of the predictors on romantic relationship closeness. Results supported the beneficial effects of both resilience and receiving high-quality support, although the timing of the injury moderated these effects. Injuries sustained after relationship initiation particularly threaten well-being and closeness and, along with the burden of caregiving tasks, alter the extent to which received support and resilience are associated with health and relationship benefits. These results suggest that support providers should be sensitive to the context of the SCI and, for scholars, indicate the importance of further theorizing context in the theory of resilience and relational load.

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Beneficial effects of nitric oxide synthase inhibition on the recovery of neurological function after spinal cord injury in rats

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s002100000317 ◽

2001 ◽

Vol 363 (1) ◽

pp. 94-100 ◽

Cited By ~ 17

Author(s):

Toshio Suzuki ◽

Hozumi Tatsuoka ◽

Tanemichi Chiba ◽

Toshihiko Sekikawa ◽

Tetsuharu Nemoto ◽

...

Keyword(s):

Nitric Oxide ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Nitric Oxide Synthase ◽

Neurological Function ◽

Beneficial Effects ◽

Cord Injury ◽

Oxide Synthase

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Mutually beneficial effects of intensive exercise and GABAergic neural progenitor cell transplants in reducing neuropathic pain and spinal pathology in rats with spinal cord injury

Experimental Neurology ◽

10.1016/j.expneurol.2020.113208 ◽

2020 ◽

Vol 327 ◽

pp. 113208 ◽

Cited By ~ 2

Author(s):

Elizabeth A. Dugan ◽

Stanislava Jergova ◽

Jacqueline Sagen

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Progenitor Cell ◽

Neural Progenitor Cell ◽

Neural Progenitor ◽

Beneficial Effects ◽

Intensive Exercise ◽

Cord Injury ◽

Cell Transplants

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Regenerative therapy for spinal cord injury using iPSC technology

Inflammation and Regeneration ◽

10.1186/s41232-020-00149-0 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Narihito Nagoshi ◽

Hideyuki Okano ◽

Masaya Nakamura

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Chronic Phase ◽

Regenerative Therapy ◽

Spinal Cord Regeneration ◽

Gamma Secretase ◽

Safety Issues ◽

Beneficial Effects ◽

Cord Injury ◽

Induced Pluripotent

Abstract Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Because the protocol to produce human induced pluripotent stem cells (iPSCs) was first established, we have attempted to apply this technology for regenerative therapy in SCI. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. Current transplantation therapies treat patients at the subacute phase after injury, highlighting the need for effective treatments for chronic SCI. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.

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HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery

International Journal of Molecular Sciences ◽

10.3390/ijms21124539 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4539

Author(s):

Sven Hendrix ◽

Selien Sanchez ◽

Elissia Ventriglia ◽

Stefanie Lemmens

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Valproic Acid ◽

Side Effects ◽

Histone Deacetylase ◽

Functional Recovery ◽

Hdac Inhibition ◽

Beneficial Effects ◽

Cord Injury ◽

Classically Activated

Pan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that HDAC8 inhibition improves functional recovery after SCI by reducing pro-inflammatory classically activated Mφ. Specific HDAC8 inhibition with PCI-34051 reduced the numbers of perilesional Mφ as measured by histological analyses, but did not improve functional recovery (Basso Mouse Scale). We could not reproduce the published improvement of functional recovery described in contusion SCI models using VPA in our T-cut hemisection SCI model. The presence of spared fibers might be the underlying reason for the conflicting data in different SCI models.

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