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  4. Local delivery of RhoA siRNA by PgP nanocarrier reduces inflammatory response and improves neuronal cell survival in a rat TBI model

Local delivery of RhoA siRNA by PgP nanocarrier reduces inflammatory response and improves neuronal cell survival in a rat TBI model

Nanomedicine, 2021 · DOI: 10.1016/j.nano.2020.102343 · Published: February 1, 2021

NeurologyGeneticsBiomedical

Simple Explanation

Traumatic brain injury (TBI) is a major cause of death and disability. This study explores a new way to reduce the damage that occurs after a TBI by using tiny particles called nanocarriers to deliver a special molecule (siRNA) that targets a specific protein (RhoA) involved in inflammation and cell death. The researchers used a rat model of TBI and injected the nanocarriers containing the siRNA directly into the injured brain tissue. They found that this treatment reduced inflammation, decreased the size of the brain lesion, and improved the survival of brain cells. These findings suggest that using nanocarriers to deliver siRNA targeting RhoA could be a promising new approach to treat TBI and reduce the long-term consequences of this type of injury.

Study Duration
7 days
Participants
Male Sprague Dawley rats (~350 g)
Evidence Level
Not specified

Key Findings

  • 1
    PgP/siRhoA nanoplexes efficiently knockdown RhoA expression in the injured brain tissue, both at the mRNA and protein levels.
  • 2
    Treatment with PgP/siRhoA nanoplexes resulted in a significant reduction in lesion volume compared to untreated TBI animals.
  • 3
    PgP/siRhoA nanoplex treatment significantly decreased cellular apoptosis and improved neuron cell survival in the ipsilateral cortex.

Research Summary

This study investigates the effect of RhoA knockdown by PgP/siRhoA nanoplexes on neuroinflammation and neuronal cell survival in a rat controlled cortical impact (CCI) TBI model in vivo. RhoA knockdown by intraparenchymal injection of PgP/siRhoA nanoplexes in the injury site resulted in decreased lesion volume, inflammatory response, and apoptosis and increased neuronal cell survival compared to untreated TBI animals at 7 days post-injury (DPI). The results suggest that local delivery of RhoA siRNA by PgP nanocarriers can be an effective strategy for reducing secondary injury and improving outcomes after TBI.

Practical Implications

Therapeutic Target

RhoA/ROCK signaling pathway is an important target for pharmacological intervention in TBI.

Delivery Method

PgP nanocarriers can efficiently bind and protect siRNA cargo, mediating efficient knockdown of RhoA in the injured brain.

Clinical Potential

Targeted combinatorial therapeutic delivery carrier for siRNA and drugs to improve motor and cognitive function recovery in TBI.

Study Limitations

  • 1
    The study was conducted on a rat model, and the results may not be directly applicable to humans.
  • 2
    The study only evaluated the effects of treatment at 7 days post-injury. Long-term effects were not assessed.
  • 3
    The synergistic effect of siRhoA and rolipram on secondary injury and functional recovery needs further evaluation.

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