A review of emerging neuroprotective and neuroregenerative therapies in traumatic spinal cord injury

Hejrati, Nader; Fehlings, Michael G.

doi:10.1016/j.coph.2021.08.009

Cited by 38 publications

(25 citation statements)

References 71 publications

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“…Traumatic SCI in China showed an increasing trend from 2009 to 2018, with an estimated 66.5 cases/million population (95% confidence interval, 65.2–67.8) (Hao et al, 2021 ). SCI can impose an enormous physical, emotional, and financial burden on patients, families, and society (Badhiwala et al, 2019 ; Hejrati and Fehlings, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis

Liang

Lin

et al. 2022

Front. Cell. Neurosci.

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ObjectiveTo compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).DesignA systematic review and Bayesian network meta-analysis.Data SourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials.Study SelectionWe included randomized controlled trials, case–control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.ResultsForty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0–0.91, low certainty) and FIM score at 12 months (42.83, 36.33–49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15–0.73, moderate certainty), the motor score at 6 months (4.43, 0.91–7.78, moderate certainty), light touch at 6 (10.01, 5.81–13.88, moderate certainty) and 12 months (11.48, 6.31–16.64, moderate certainty), pinprick score at 6 (14.54, 9.76–19.46, moderate certainty) and 12 months (12.48, 7.09–18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62–6.97, moderate certainty) and 12 months (5.54, 2.45–8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71–17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.ConclusionsPatients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.

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Section: Introductionmentioning

confidence: 99%

“…Neuroprotection and nerve regeneration therapy are important SCI treatments. Currently, nerve regeneration therapy measures used for SCI treatment include pharmacological therapy, cell transplantation, biological scaffolds, and neuromodulatory agents (Hejrati and Fehlings, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis

Liang

Lin

et al. 2022

Front. Cell. Neurosci.

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“…Due to the low innate regenerative ability of the spinal cord, recovery in SCI patients is usually incomplete, and the current therapies are limited in their efficacy [ 11 ]. Due to this grim situation, therapies targeting neuroprotection and neuroregeneration after SCI are an active area of research [ 13 , 14 ]. Due to its prominent role in cellular homeostasis, cellular stress responses, and programmed cell death, the modulation of autophagy presents a promising avenue for the treatment of SCI.…”

Section: Introductionmentioning

confidence: 99%

Specific microRNAs for Modulation of Autophagy in Spinal Cord Injury

Visintin

Ray

2022

Brain Sciences

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The treatment of spinal cord injury (SCI) is currently a major challenge, with a severe lack of effective therapies for yielding meaningful improvements in function. Therefore, there is a great opportunity for the development of novel treatment strategies for SCI. The modulation of autophagy, a process by which a cell degrades and recycles unnecessary or harmful components (protein aggregates, organelles, etc.) to maintain cellular homeostasis and respond to a changing microenvironment, is thought to have potential for treating many neurodegenerative conditions, including SCI. The discovery of microRNAs (miRNAs), which are short ribonucleotide transcripts for targeting of specific messenger RNAs (mRNAs) for silencing, shows prevention of the translation of mRNAs to the corresponding proteins affecting various cellular processes, including autophagy. The number of known miRNAs and their targets continues to grow rapidly. This review article aims to explore the relationship between autophagy and SCI, specifically with the intent of identifying specific miRNAs that can be useful to modulate autophagy for neuroprotection and the improvement of functional recovery in SCI.

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“…That is why fundamental and preclinical studies have been conducted over the last several decades to find innovative therapies [ 1 ]. Research studies have followed different paths; the first one tried to modulate the inhibitory microenvironment present after SCI, and the second one harnessed to replace the lost cells, such as neurons or oligodendrocytes [ 2 ]. These two strategies are based on the knowledge acquired about the cellular and molecular events that take place after SCI.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, at the cellular level, SCI induces a massive inflammation with the infiltration of circulating immune cells, such as macrophages, and induction of microglia reactivity [ 3 ]. At the same time, the initial traumatic injury leads to neuronal and oligodendroglial death [ 2 , 4 ]. Altogether, these cellular events lead to the formation of a spinal scar composed of a fibrotic core that is present in the lesion epicenter and of an astroglial scar located at the border of the lesion [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Repetitive Trans Spinal Magnetic Stimulation Improves Functional Recovery and Tissue Repair in Contusive and Penetrating Spinal Cord Injury Models in Rats

et al. 2021

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Spinal cord injury (SCI) is an incurable condition in which the brain is disconnected partially or completely from the periphery. Mainly, SCIs are traumatic and are due to traffic, domestic or sport accidents. To date, SCIs are incurable and, most of the time, leave the patients with a permanent loss of sensitive and motor functions. Therefore, for several decades, researchers have tried to develop treatments to cure SCI. Among them, recently, our lab has demonstrated that, in mice, repetitive trans-spinal magnetic stimulation (rTSMS) can, after SCI, modulate the lesion scar and can induce functional locomotor recovery non-invasively. These results are promising; however, before we can translate them to humans, it is important to reproduce them in a more clinically relevant model. Indeed, SCIs do not lead to the same cellular events in mice and humans. In particular, SCIs in humans induce the formation of cystic cavities. That is why we propose here to validate the effects of rTSMS in a rat animal model in which SCI leads to the formation of cystic cavities after penetrating and contusive SCI. To do so, several techniques, including immunohistochemical, behavioral and MRI, were performed. Our results demonstrate that rTSMS, in both SCI models, modulates the lesion scar by decreasing the formation of cystic cavities and by improving axonal survival. Moreover, rTSMS, in both models, enhances functional locomotor recovery. Altogether, our study describes that rTSMS exerts positive effects after SCI in rats. This study is a further step towards the use of this treatment in humans.

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A review of emerging neuroprotective and neuroregenerative therapies in traumatic spinal cord injury

Cited by 38 publications

References 71 publications

Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis

Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis

Specific microRNAs for Modulation of Autophagy in Spinal Cord Injury

Repetitive Trans Spinal Magnetic Stimulation Improves Functional Recovery and Tissue Repair in Contusive and Penetrating Spinal Cord Injury Models in Rats

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