Abstract

Multiple therapies have been studied to ameliorate the neuroinhibitory cues present after traumatic injury to the central nervous system. Two previous in vitro studies have demonstrated the efficacy of the Food and Drug Administration-approved cardiovascular therapeutic, protamine (PRM), to overcome neuroinhibitory cues presented by chondroitin sulfates; however, the effect of a wide range of PRM concentrations on neuronal and glial cells has not been evaluated. In this study, we investigate the therapeutic efficacy of PRM with primary cortical neurons, hippocampal neurons, mixed glial cultures, and astrocytes. The threshold for PRM toxicity is shown to be at or above 10 µg mL−1 depending on the cell population, that 10 µg mL−1 PRM enables neurons to overcome the inhibitory cues presented by chondroitin sulfate type A, and that soluble PRM allows neurons to more effectively overcome inhibition compared to a PRM coating. Changes in gene expression of reactive astrocytes is also assessed with soluble PRM and it is determined that PRM does not increase their neurotoxic phenotype and that PRM may reduce brevican and serpin transcription in cortical and spinal cord astrocytes. This is the first study to thoroughly assess the toxicity threshold of PRM with neural cells and study astrocyte response after acute exposure to PRM in vitro.

Department(s)

Chemical and Biochemical Engineering

Publication Status

Full Access

Comments

National Science Foundation, Grant 32245GG

Keywords and Phrases

astrocyte reactivity; drug toxicity; neurotherapy; protamine sulfate salt; traumatic central nervous system injury

International Standard Serial Number (ISSN)

2366-3987

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 Wiley, All rights reserved.

Publication Date

01 Feb 2024

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