4.7 Article

Therapeutic efficacy of Rolipram delivered by PgP nanocarrier on secondary injury and motor function in a rat TBI model

Journal

NANOMEDICINE
Volume 17, Issue 7, Pages 431-445

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2021-0271

Keywords

apoptosis; controlled cortical impact; functional recovery; neuroinflammation; PgP nanoparticle; rolipram; traumatic brain injury

Funding

  1. National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) [5P20GM103444-07]
  2. National Institute of Neurological Disorders and Strokes (NINDS) of the NIH [5R01 NS111037-02]

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In this study, a nanocarrier PgP was developed for the delivery of Rm and its therapeutic efficacy on secondary injury and motor function in a TBI model was evaluated. The results showed that Rm-PgP restored cAMP level, reduced lesion volume and neuroinflammation, and improved motor function. This suggests the potential of a single injection of Rm-PgP for acute mild TBI treatment.
Aim: To develop poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) as a nanocarrier for the delivery of Rolipram (Rm) and evaluate the therapeutic efficacy of Rm-loaded PgP (Rm-PgP) on secondary injury and motor function in a rat traumatic brain injury (TBI) model. Materials & methods: Rm-PgP was injected in the injured brain lesion immediately after TBI using a microinjection pump. Secondary injury pathologies such as inflammatory response, apoptosis and astrogliosis were assessed by histological analysis and functional recovery was assessed by assorted motor function tests. Results: Rm-PgP restored cyclic adenosine monophosphate level in the injured brain close to the sham level and Rm-PgP treatment reduced lesion volume, neuroinflammation and apoptosis and improved motor function at 7 days post-TBI. Conclusion: One single injection of Rm-PgP can be effective for acute mild TBI treatment.

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