Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

Nguyen, Ashley; Chow, Diana; Wu, Lei; Teng, Yang; Sarkar, Mahua; Toups, Elizabeth G.; Schmitt, Karl; Johnson, Mai; Guest, James D.; Aarabi, Bizhan; Shaffrey, Christopher I.; Boakye, Maxwell; Frankowski, Ralph F.; Fehlings, Michael G.; Grossman, Robert G.

doi:10.1002/jcph.1876

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…It is often used to treat amyotrophic lateral sclerosis (ALS) neurodegeneration. It has been found to be safe and effective in people with SCI, which was proven in a phase 1 clinical trial (Nguyen et al, 2021). Daverey and Agrawal (2020) found that riluzole exerts a neuroprotective effect on astrocytes and white matter of SCI by activating the Nrf2/HO-1 signaling pathway.…”

Section: Riluzolementioning

confidence: 96%

Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options

Jiang

He²

2022

Front. Aging Neurosci.

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Nuclear factor erythroid-2-related factor 2 (Nrf2) is a pleiotropic transcription factor, and it has been documented that it can induce defense mechanisms both oxidative stress and inflammatory injury. At present, more and more evidences show that the Nrf2 signaling pathway is a key pharmacological target for the treatment of spinal cord injury (SCI), and activating the Nrf2 signaling pathway can effectively treat the inflammatory injury and oxidative stress after SCI. This article firstly introduces the biological studies of the Nrf2 pathway. Meanwhile, it is more powerful to explain that activating the Nrf2 signaling pathway can effectively treat SCI by deeply exploring the relationship between Nrf2 and oxidative stress, inflammatory injury, and SCI. In addition, several potential drugs for the treatment of SCI by promoting Nrf2 activation and Nrf2-dependent gene expression are reviewed. And some other treatment strategies of SCI by modulating the Nrf2 pathway are also summarized. It will provide new ideas and directions for the treatment of SCI.

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Section: Riluzolementioning

confidence: 96%

Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options

Jiang

He²

2022

Front. Aging Neurosci.

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“…Other potential medications have been suggested to mediate edema reduction and have been tested or are currently under investigation in clinical stages for acute management of spinal cord in phases II–III [ 112 , 113 ]. For example, clinical trials have been conducted on GM1 (monosialotetrahexosyl) ganglioside [ 114 ], minocycline [ 115 ], riluzole [ 116 , 117 , 118 ] and granulocyte colony stimulating factor [ 119 , 120 ]. However, these are investigated for their neuroprotective and anti-inflammatory effects in acute phase without being linked specifically to edema mechanisms.…”

Section: Toward a Further Treatment Of Spinal Cord Edemamentioning

confidence: 99%

Edema after CNS Trauma: A Focus on Spinal Cord Injury

Seblani

Decherchi

Brezun

2023

IJMS

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Edema after spinal cord injury (SCI) is one of the first observations after the primary injury and lasts for few days after trauma. It has serious consequences on the affected tissue and can aggravate the initial devastating condition. To date, the mechanisms of the water content increase after SCI are not fully understood. Edema formation results in a combination of interdependent factors related to mechanical damage after the initial trauma progressing, along with the subacute and acute phases of the secondary lesion. These factors include mechanical disruption and subsequent inflammatory permeabilization of the blood spinal cord barrier, increase in the capillary permeability, deregulation in the hydrostatic pressure, electrolyte-imbalanced membranes and water uptake in the cells. Previous research has attempted to characterize edema formation by focusing mainly on brain swelling. The purpose of this review is to summarize the current understanding of the differences in edema formation in the spinal cord and brain, and to highlight the importance of elucidating the specific mechanisms of edema formation after SCI. Additionally, it outlines findings on the spatiotemporal evolution of edema after spinal cord lesion and provides a general overview of prospective treatment strategies by focusing on insights to prevent edema formation after SCI.

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“…Medication was administered orally or by nasogastric tube. This trial showed some improved ASIA motor scores associated with the treatment and provided the impetus for a phase IIb/III double-blinded, placebo-controlled trial [Riluzole in Acute Spinal Cord Injury Study (RISCIS)] [125,126]. In the phase III trial, 351 patients were enrolled and randomized in a 1:1 ratio to riluzole or placebo.…”

Section: Molecular Therapymentioning

confidence: 99%

Pathophysiology and Therapeutic Approaches for Spinal Cord Injury

Lima

Monteiro

Salgado

et al. 2022

IJMS

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Spinal cord injury (SCI) is a disabling condition that disrupts motor, sensory, and autonomic functions. Despite extensive research in the last decades, SCI continues to be a global health priority affecting thousands of individuals every year. The lack of effective therapeutic strategies for patients with SCI reflects its complex pathophysiology that leads to the point of no return in its function repair and regeneration capacity. Recently, however, several studies started to uncover the intricate network of mechanisms involved in SCI leading to the development of new therapeutic approaches. In this work, we present a detailed description of the physiology and anatomy of the spinal cord and the pathophysiology of SCI. Additionally, we provide an overview of different molecular strategies that demonstrate promising potential in the modulation of the secondary injury events that promote neuroprotection or neuroregeneration. We also briefly discuss other emerging therapies, including cell-based therapies, biomaterials, and epidural electric stimulation. A successful therapy might target different pathologic events to control the progression of secondary damage of SCI and promote regeneration leading to functional recovery.

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Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent

Cited by 4 publications

References 38 publications

Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options

Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options

Edema after CNS Trauma: A Focus on Spinal Cord Injury

Pathophysiology and Therapeutic Approaches for Spinal Cord Injury

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