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Rolipram-Loaded PgP Nanotherapeutics via Intrathecal Administration Reduces Secondary Injury in a Rat Acute Moderate Contusion SCI Model
Journal article   Open access   Peer reviewed

Rolipram-Loaded PgP Nanotherapeutics via Intrathecal Administration Reduces Secondary Injury in a Rat Acute Moderate Contusion SCI Model

Zhen Liao, Jun Gao, Min Kyung Khang, Ken Webb, Megan Ryan Detloff and Jeoung Soo Lee
Journal of neuroscience research, v 103(11), e70091
Nov 2025
DOI: https://doi.org/10.1002/jnr.70091
PMID: 41192818
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1002/jnr.70091View
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Abstract

Animals Cyclic AMP - metabolism Disease Models, Animal Female Injections, Spinal Male Nanoparticles - administration & dosage Phosphodiesterase 4 Inhibitors - administration & dosage Polyethyleneimine - administration & dosage Rats Rats, Sprague-Dawley Recovery of Function - drug effects Rolipram - administration & dosage Spinal Cord Injuries - drug therapy Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology
Spinal cord injury (SCI) triggers complex secondary injury mechanisms, resulting in long-term impacts on sensory and motor function. Rolipram, a phosphodiesterase-4 inhibitor, has shown promise in preserving/restoring cyclic adenosine monophosphate (cAMP) to reduce secondary injury responses, but its clinical application is hindered by poor solubility and systemic side effects. To overcome these challenges, we developed rolipram-loaded poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) nanoparticles (Rm-PgP) to enable localized and sustained drug delivery. In our previous findings, Rm-PgP administered via intraspinal injection restored cAMP levels at the lesion site, and reduced secondary injury after moderate, contusive SCI. In this study, we investigated the effect of single and repeat administration of Rm-PgP by the clinically relevant intrathecal route immediately after injury. We observed that the hydrophobic dye, DiR-loaded PgP (DiR-PgP) was retained in the CNS over 7 days post-injury (DPI). In addition, we observed that both single and repeat Rm-PgP treatment groups showed higher cAMP levels compared to those in the untreated SCI group and only the single treatment group showed a significant difference compared to the untreated SCI group. Lastly, we observed that cAMP restoration in both single and repeat Rm-PgP treatment groups showed higher levels of activated cAMP-response element-binding protein (pCREB) relative to the untreated control. We also observed that both Rm-PgP treatment groups showed reduced inflammatory response, reduced astrogliosis and apoptosis, and increased neuronal survival and spared tissue volume. These findings highlight the neuroprotective efficacy of Rm-PgP by intrathecal administration in mitigating secondary injury during the critical early phase of recovery after SCI.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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