Pharmacological Neuroprotective Therapy for Acute Spinal Cord Injury: State of the Art

Martiñón, S.; Ibarra, Antonio

doi:10.2174/138955708783744056

Cited by 17 publications

(10 citation statements)

References 127 publications

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“…Minocycline is perhaps the compound with the most possibilities of being tested in clinical trials. It is a tetracycline that crosses the blood-brain barrier and prevents caspase upregulation, thus preventing this apoptotic phenomenon [29]. …”

Section: Discussionmentioning

confidence: 99%

Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Rodríguez-Barrera

Fernández-Presas

García

et al. 2013

BioMed Research International

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Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-α concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy.

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Section: Discussionmentioning

confidence: 99%

Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Rodríguez-Barrera

Fernández-Presas

García

et al. 2013

BioMed Research International

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“…2 A) [ 38 , 40 , 41 ]. However, two experiments utilizing enzyme-linked immunosorbent assays (ELISAs) to measure IL-1β did not observe an increase at this early timepoint [ 42 , 43 ], which may be the result of the discrepancy in time needed to synthesize the full protein and the time needed for it to be proteolytically processed to its active form by caspase 1 [ 44 ]. There were very similar trends in the early IL-6 upregulation to that of IL-1β (Fig.…”

Section: Main Textmentioning

confidence: 99%

Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

Hellenbrand

Quinn

Piper

et al. 2021

J Neuroinflammation

258

175

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Traumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.

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“…1) causes disruption of neural tissue (mainly axons) and blood vessels. The primary mechanical trauma to the spinal cord triggers a secondary pathological cascade of biochemical and neurological events that may continue to progress on the order of minutes to months [5]. These secondary events involve a intricacy cascade of molecular events that incorporate disturbances of ionic homeostasis, local oedema, ischaemia, focal haemorrhage, free radical stress and a robust inflammatory responses in early acute stage, which is considered to last from 2h to 2d following SCI [3,52,53] (Table 1).…”

Section: Pathophysiology Of Sci and The Targets For Fgf Treatmentmentioning

confidence: 99%

“…The subsequent secondary damage starts from the early acute phase and even last months after SCI [54]. Extensive nervous cell death and cavitation of central grey matter and activation of protoplasmic astrocytes, glial scar occur during the secondary [5]. At the subacute stage after SCI, the delayed secondary damage is characterized by phagocytosis, neuronal and oligodendroglial apoptosis and demyelination followed by cyst formation [54].…”

Section: Pathophysiology Of Sci and The Targets For Fgf Treatmentmentioning

confidence: 99%

“…Intensive efforts are underway to develop effective neuroprotective and neuroregenerative strategies. Current therapies for improving clinical outcome include limiting inflammation, preventing secondary cell death and enhancing the plasticity of spared circuits [1,5,6]. At present, however, there are no universally accepted treatments for this neurological disorder.…”

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factors in the management of spinal cord injury

Zhou

Wang

et al. 2017

J Cellular Molecular Medi

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Spinal cord injury (SCI) possesses a significant health and economic burden worldwide. Traumatic SCI is a devastating condition that evolves through two successive stages. Throughout each of these stages, disturbances in ionic homeostasis, local oedema, ischaemia, focal haemorrhage, free radicals stress and inflammatory response were observed. Although there are no fully restorative cures available for SCI patients, various molecular, cellular and rehabilitative therapies, such as limiting local inflammation, preventing secondary cell death and enhancing the plasticity of local circuits in the spinal cord, were described. Current preclinical studies have showed that fibroblast growth factors (FGFs) alone or combination therapies utilizing cell transplantation and biomaterial scaffolds are proven effective for treating SCI in animal models. More importantly, some studies further demonstrated a paucity of clinical transfer usage to promote functional recovery of numerous patients with SCI. In this review, we focus on the therapeutic capacity and pitfalls of the FGF family and its clinical application for treating SCI, including the signalling component of the FGF pathway and the role in the central nervous system, the pathophysiology of SCI and the targets for FGF treatment. We also discuss the challenges and potential for the clinical translation of FGF‐based approaches into treatments for SCI.

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Pharmacological Neuroprotective Therapy for Acute Spinal Cord Injury: State of the Art

Cited by 17 publications

References 127 publications

Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

Fibroblast growth factors in the management of spinal cord injury

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