Sustained delivery of chABC improves functional recovery after a spine injury

Sharifi, Atousa; Zandieh, Ali; Behroozi, Zahra; Hamblin, Michael R.; Mayahi, Sara; Yousefifard, Mahmoud; Ramezani, Fatemeh

doi:10.1186/s12868-022-00734-8

Cited by 18 publications

(7 citation statements)

References 64 publications

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“…Cellular/molecular therapeutic strategies currently investigated for SCI regeneration target the glial scar and promote regeneration in the following ways: (1) targeting scar formation; (2) resolving the mature scar; (3) cell transplantation; and (4) endogenous cell reprogramming. Locomotor functional recovery has been observed in rodent SCI model behavioral assessments of therapeutics in each of these major groups [ 86 , 95 , 119 , 143 , 147 ]. However, few therapeutics successfully translate to clinical trials; thus, SCI remains a debilitating injury.…”

Section: Discussionmentioning

confidence: 99%

“…CSPGs are ubiquitous and abundant around the scar and possess a known degradation enzyme [ 91 , 93 , 94 ]. The upregulation or administration of CSPG enzyme ChABC, a bacterial lyase which degrades CSPG side chains, yielded functional recovery in a rodent SCI model [ 92 , 95 ]. However, the high enzyme degradation rate (within 24 h) was considered to be a major limiting factor preceding clinical trials, thus methods of biotechnology are being employed to extend the stability of the enzyme around the injury site.…”

Section: Current Research In Therapeutic Interventionsmentioning

confidence: 99%

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Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Clifford

Finkel

Rodriguez

et al. 2023

Cells

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Spinal cord injury (SCI) is a complex tissue injury resulting in permanent and degenerating damage to the central nervous system (CNS). Detrimental cellular processes occur after SCI, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, and scar formation. The glial scar border forms to segregate the neural lesion and isolate spreading inflammation, reactive oxygen species, and excitotoxicity at the injury epicenter to preserve surrounding healthy tissue. The scar border is a physicochemical barrier composed of elongated astrocytes, fibroblasts, and microglia secreting chondroitin sulfate proteoglycans, collogen, and the dense extra-cellular matrix. While this physiological response preserves viable neural tissue, it is also detrimental to regeneration. To overcome negative outcomes associated with scar formation, therapeutic strategies have been developed: the prevention of scar formation, the resolution of the developed scar, cell transplantation into the lesion, and endogenous cell reprogramming. This review focuses on cellular/molecular aspects of glial scar formation, and discusses advantages and disadvantages of strategies to promote regeneration after SCI.

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Section: Discussionmentioning

confidence: 99%

Section: Current Research In Therapeutic Interventionsmentioning

confidence: 99%

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Clifford

Finkel

Rodriguez

et al. 2023

Cells

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“…As reported previously, early therapeutic approaches in the management of SCI lead to better outcomes and fewer postoperative complications, both in clinical and preclinical evidence. [68][69][70][71] Even though we aimed at summarizing the evidence from both animal and human populations, our search resulted in no clinical research that would meet our inclusion criteria. The chronic shoulder pain and generally perceived pain that was evaluated in previous RCTs could have etiologies other than neuropathic pain, and their inclusion is considered an ancillary analysis in this meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

The Role of Exercise in the Alleviation of Neuropathic Pain Following Traumatic Spinal Cord Injuries: A Systematic Review and Meta-analysis

Toloui,

Ramawad,

Gharin

et al. 2023

Neurospine

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Objective: The objective of this systematic review and meta-analysis was to assess the efficacy of exercise in neuropathic pain following traumatic spinal cord injuries.Methods: The search was conducted in MEDLINE, Embase, Scopus, and Web of Science by the end of 2022. Two independent researchers included the articles based on the inclusion and exclusion criteria. A standardized mean difference was calculated for each data and they were pooled to calculate an overall effect size. To assess the heterogeneity between studies, I<sup>2</sup> and chi-square tests were utilized. In the case of heterogeneity, meta-regression was performed to identify the potential source.Results: Fifteen preclinical studies were included. Meta-analysis demonstrated that exercise significantly improves mechanical allodynia (standardized mean difference [SMD], -1.59; 95% confidence interval [CI], -2.16 to -1.02; p < 0.001; I<sup>2</sup> = 90.37%), thermal hyperalgesia (SMD, 1.95; 95% CI, 0.96–2.94; p < 0.001), and cold allodynia (SMD, -2.92; 95% CI, -4.4 to -1.43; p < 0.001). The improvement in mechanical allodynia is significantly more in animals with a compression model of SCI (meta-regression coefficient, -1.33; 95% CI, -1.84 to -0.57; p < 0.001) and in mild SCI (p < 0.001). Additionally, the improvement was more prominent if the training was started 7 to 8 days postinjury (coefficient, -2.54; 95% CI, -3.85 to -1.23; p < 0.001) and was continued every day (coefficient, -1.99; 95% CI, -3.07 to -0.9; p < 0.001). Likewise, voluntary exercise demonstrated a significantly more effect size (coefficient, -1.45; 95% CI, -2.67 to -0.23; p = 0.02).Conclusion: Exercise is effective in the amelioration of neuropathic pain. This effect in mechanical allodynia is more prominent if voluntary, continuous training is initiated in the subacute phase of mild SCI.

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“…The research at present focuses on the therapeutic strategies that target these inhibitory pathways. For example, Chondroitinase ABC degrades CSPGs, improving axonal regeneration in animal models [ 102 , 103 , 104 ]. Pharmaceutical agents targeting RhoA/ROCK and other signaling pathways have also shown potential [ 105 , 106 ].…”

Section: Current Challenges In the Treatment Of Scismentioning

confidence: 99%

The Promising Role of a Zebrafish Model Employed in Neural Regeneration Following a Spinal Cord Injury

Zeng,

Tsai

2023

IJMS

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Spinal cord injury (SCI) is a devastating event that results in a wide range of physical impairments and disabilities. Despite the advances in our understanding of the biological response to injured tissue, no effective treatments are available for SCIs at present. Some studies have addressed this issue by exploring the potential of cell transplantation therapy. However, because of the abnormal microenvironment in injured tissue, the survival rate of transplanted cells is often low, thus limiting the efficacy of such treatments. Many studies have attempted to overcome these obstacles using a variety of cell types and animal models. Recent studies have shown the utility of zebrafish as a model of neural regeneration following SCIs, including the proliferation and migration of various cell types and the involvement of various progenitor cells. In this review, we discuss some of the current challenges in SCI research, including the accurate identification of cell types involved in neural regeneration, the adverse microenvironment created by SCIs, attenuated immune responses that inhibit nerve regeneration, and glial scar formation that prevents axonal regeneration. More in-depth studies are needed to fully understand the neural regeneration mechanisms, proteins, and signaling pathways involved in the complex interactions between the SCI microenvironment and transplanted cells in non-mammals, particularly in the zebrafish model, which could, in turn, lead to new therapeutic approaches to treat SCIs in humans and other mammals.

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Sustained delivery of chABC improves functional recovery after a spine injury

Cited by 18 publications

References 64 publications

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

The Role of Exercise in the Alleviation of Neuropathic Pain Following Traumatic Spinal Cord Injuries: A Systematic Review and Meta-analysis

The Promising Role of a Zebrafish Model Employed in Neural Regeneration Following a Spinal Cord Injury

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