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Updated: Jan 12, 2026

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury
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Rolipram-Loaded PgP Nanotherapeutics via Intrathecal Administration Reduces Secondary Injury in a Rat Acute Moderate

Zhen Liao1, Jun Gao1, Min Kyung Khang1

  • 1Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.

Journal of Neuroscience Research
|November 5, 2025
PubMed
Summary
This summary is machine-generated.

This study shows that rolipram-loaded nanoparticles delivered intrathecally after spinal cord injury (SCI) reduce secondary injury by restoring cyclic adenosine monophosphate (cAMP) levels, promoting neuroprotection and tissue sparing.

Keywords:
apoptosisastrogliosisnanocarrierneuroinflammationneuronal survivalrolipramspinal cord injury

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Pharmacology

Background:

  • Spinal cord injury (SCI) causes secondary injury, leading to long-term sensory and motor deficits.
  • Rolipram, a PDE4 inhibitor, can reduce SCI by restoring cyclic adenosine monophosphate (cAMP), but faces delivery challenges.
  • Poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) nanoparticles offer a solution for localized, sustained drug delivery.

Purpose of the Study:

  • To evaluate the neuroprotective effects of rolipram-loaded PgP nanoparticles (Rm-PgP) administered intrathecally immediately after SCI.
  • To assess the impact of single and repeat Rm-PgP administration on secondary injury mechanisms and outcomes.

Main Methods:

  • Developed Rm-PgP nanoparticles for localized delivery of rolipram.
  • Administered Rm-PgP intrathecally in a rat SCI model.
  • Quantified nanoparticle retention in the central nervous system (CNS).
  • Measured cAMP levels, activated cAMP-response element-binding protein (pCREB), inflammatory markers, astrogliosis, apoptosis, neuronal survival, and spared tissue volume.

Main Results:

  • Intrathecal Rm-PgP demonstrated sustained CNS retention over 7 days post-injury.
  • Both single and repeat Rm-PgP treatments increased cAMP levels compared to untreated SCI.
  • Rm-PgP treatment upregulated pCREB and reduced inflammation, astrogliosis, and apoptosis.
  • Significant improvements in neuronal survival and spared tissue volume were observed in Rm-PgP treated groups.

Conclusions:

  • Intrathecal administration of Rm-PgP is a promising strategy for mitigating secondary injury after SCI.
  • This localized delivery approach enhances neuroprotection and promotes tissue sparing during the critical early recovery phase.