Rolipram-Loaded Polymeric Micelle Nanoparticle Reduces Secondary Injury after Rat Compression Spinal Cord Injury

Abstract

Among the complex pathophysiological events following spinal cord injury (SCI), one of the most important molecular level consequences is a dramatic reduction in neuronal cyclic adenosine monophosphate (cAMP) levels. Many studies shown that rolipram (Rm), a phosphodiesterase IV inhibitor, can protect against secondary cell death, reduce inflammatory cytokine levels and immune cell infiltration, and increase white matter sparing and functional improvement. Previously, we developed a polymeric micelle nanoparticle, poly(lactide-co-glycolide)-graft-polyethylenimine (PgP), for combinatorial delivery of therapeutic nucleic acids and drugs for SCI repair. In this study, we evaluated PgP as an Rm delivery carrier for SCI repair. Rolipram's water solubility was increased ∼6.8 times in the presence of PgP, indicating drug solubilization in the micelle hydrophobic core. Using hypoxia as an in vitro SCI model, Rm-loaded PgP (Rm-PgP) restored cAMP levels and increased neuronal cell survival of cerebellar granular neurons. The potential efficacy of Rm-PgP was evaluated in a rat compression SCI model. After intraspinal injection, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine Iodide-loaded PgP micelles were retained at the injection site for up to 5 days. Finally, we show that a single injection of Rm-PgP nanoparticles restored cAMP in the SCI lesion site and reduced apoptosis and the inflammatory response. These results suggest that PgP may offer an efficient and translational approach to delivering Rm as a neuroprotectant following SCI.

AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

“…To validate the role of AMPK‐dependent induction of autophagy in EPO's neuroprotection, we performed the in vitro study. PC12 cells (an extensively used neuronal cell line) were cultured in hypoxia condition as an in vitro neuronal injury model. CCK8 assay showed that hypoxia significantly reduced the cell viability, whereas pretreatment with EPO for 2 hours prior to hypoxia attenuated this decrease of cell viability (Figure A).…”

Evaluating accessibility of intravenously administered nanoparticles at the lesion site in rat and pig contusion models of spinal cord injury

“…Most of these approaches are for direct injection (e.g., hydrogels, nanoparticles, nanofibers, etc.) at the lesion site but few studies have also reported the use of nanomaterials for drug delivery via intravenous injection but were given immediately or within a very short time window post-injury [26,27]. As such, there is no systematic study aimed at analyzing the effect of different parameters that are critical for localization of NPs at the lesion site under clinically relevant conditions.…”

LncRNA DGCR5 suppresses neuronal apoptosis to improve acute spinal cord injury through targeting PRDM5

“…Hypoxia treatment was performed in AGE1.HN and PC12 cell lines for simulating SCI in vitro, as previously reported [14,15]. Oxygenglucose deprivation (OGD) was performed upon the above cells for hypoxia treatment in accordance with a previous study [16].…”