Galantamine improves functional recovery and reduces lesion size in a rat model of spinal cord injury

Sperling, Laura E.; Reis, Karina Pires; Nicola, Fabrício do Couto; Teixeira, Cristian; Didó, Gabriele Gulielmin; Santos, Marcelo Garrido dos; Konrath, Eduardo Luis; Netto, Carlos Alexandre; Pranke, Patrícia

doi:10.1016/j.brainres.2019.146424

Cited by 7 publications

(14 citation statements)

References 33 publications

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“…Papers published outside the 10-year time period from 2012 to 2022 were excluded, papers assessing treatments for other central nervous system injuries other than SCI were also excluded, and papers attempting to enhance delivery of a previous known treatment or attempting to replicate the results of a previous treatment were also excluded, leaving 130 articles that required a full text read to assess for eligibility. Following full text reads of these articles, the final selection of 44 studies were identified and included for analysis in this systematic review [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The literature search process and screening for eligibility is presented in the PRISMA diagram below ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

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Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis

Khan

Ahmed

2022

Cells

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Spinal cord injury (SCI) is characterized by a complex and prolonged injury process that exacerbates the damage induced by the primary injury and inhibits the potential for regeneration. SCI frequently results in the devastating loss of neurological functions and thus has serious consequences on patient quality of life. Current treatments are limited and focus on early interventions for the acute management of complications. Therefore, the development of novel treatments targeting ongoing injury processes is required to improve SCI outcomes. We aimed to systematically review studies published in the last 10 years that examined experimental treatments with neuroregenerative and neuroprotective capabilities for the improvement of SCI. We analyzed treatments from 44 studies that were identified through a systematic literature search using three databases: PubMed, Web of Science and EMBASE (searched through Ovid). We performed a meta-analysis for Basso-Beattie-Bresnahan (BBB) locomotion test data and collected immunohistochemistry results to demonstrate neuroregenerative and neuroprotective properties of the treatments, respectively. The two treatments that illustrated the most significant improvements in functional recovery using the BBB test were the combined use of tetrahedral framework nucleic acid (tFNA) with neural stem cells (NSCs) and Fortasyn® Connect (FC) supplementation. Both treatments also attenuated secondary injury processes as demonstrated through immunohistochemistry. Combined tFNA with NSCs and FC supplementation are promising treatments for the improvement of SCI as they both demonstrate neuroregenerative and neuroprotective properties. Further pre-clinical testing is required to validate and determine the long-term efficacies of these treatments for the improvement of SCI.

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Section: Resultsmentioning

confidence: 99%

“…There was 6 out of the 32 studies that reported the final BBB test score 42 days following SCI [ 19 , 32 , 46 , 48 , 51 , 53 ]. These studies were subsequently sub-grouped for a meta-analysis ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis

Khan

Ahmed

2022

Cells

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“…Prior work from other groups indicated that treatments resulting in improved recovery after SCI were associated with a reduction in cluster of differentiation 3 (CD3)-positive T cells in the spinal cord [53,54]. Thus, we investigated whether Serp-1 CCH reduced T cell invasion in the spinal cord after SCI (Figure 4).…”

Section: Treatment With Chitosan-collagen Hydrogel With Serp-1 Reducementioning

confidence: 98%

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

Kwiecień

Zhang

Yaron

et al. 2020

JCM

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Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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“…Preclinical studies have generated experimental evidence for efficacy of VNS and galantamine in SCI [85][86][87]. VNS in a closed-loop configuration combined with rehabilitative training considerably improve recovery of forelimb motor function compared with rehabilitation alone in models of contusive SCI at spinal level C5/6 [86].…”

Section: Towards Clinical Trials With Bioelectronic Vagus Nerve Stimu...mentioning

confidence: 99%

Exploring the vagus nerve and the inflammatory reflex for therapeutic benefit in chronic spinal cord injury

Bloom

Tracey

Pavlov

2022

Current Opinion in Neurology

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Purpose of reviewTo describe features and implications of chronic systemic inflammation in individuals with spinal cord injury (SCI) and to summarize the growing therapeutic possibilities to explore the vagus nerve-mediated inflammatory reflex in this context.Recent findingsThe discovery of the inflammatory reflex provides a rationale to explore neuromodulation modalities, that is, electrical vagus nerve stimulation and pharmacological cholinergic modalities to regulate inflammation after SCI.SummaryInflammation in individuals with SCI may negatively impact functional recovery and medical consequences after SCI. Exploring the potential of the vagus nerve-based inflammatory reflex to restore autonomic regulation and control inflammation may provide a novel approach for functional improvement in SCI.

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Galantamine improves functional recovery and reduces lesion size in a rat model of spinal cord injury

Cited by 7 publications

References 33 publications

Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis

Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

Exploring the vagus nerve and the inflammatory reflex for therapeutic benefit in chronic spinal cord injury

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