In Vitro Assessment of Protamine Toxicity with Neural Cells, Its Therapeutic Potential to Counter Chondroitin Sulfate Mediated Neuron Inhibition, and Its Effects on Reactive Astrocytes
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Published:2024-01-18
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Volume:
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ISSN:2366-3987
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Container-title:Advanced Therapeutics
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language:en
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Short-container-title:Advanced Therapeutics
Author:
Nelson Derek W.12ORCID,
Funnell Jessica L.12ORCID,
Cheung Conrad H.12,
Quinones Geraldine B.13,
Mendoza Christina S.13,
Bentley Marvin13ORCID,
Gilbert Ryan J.124ORCID
Affiliation:
1. Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute 1623 15th St. Troy NY 12180 USA
2. Department of Biomedical Engineering Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute 110 8th St. Troy NY 12180 USA
3. Department of Biological Sciences Rensselaer Polytechnic Institute 110 8th St. Troy NY 12180 USA
4. Albany Stratton Veteran Affairs Medical Center 113 Holland Ave. Albany NY 12208 USA
Abstract
AbstractMultiple 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.
Funder
U.S. Department of Veterans Affairs
National Science Foundation
National Institutes of Health
Subject
Pharmacology (medical),Biochemistry (medical),Genetics (clinical),Pharmaceutical Science,Pharmacology,Medicine (miscellaneous)
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