Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

Research output: Contribution to journalArticle

  • External authors:
  • Khuloud T. Al-Jamal
  • Lisa Gherardini
  • Giuseppe Bardi
  • Antonio Nunes
  • Chang Guo
  • M. Antonia Herrero
  • Alberto Bianco
  • Maurizio Prato
  • Tommaso Pizzorusso

Abstract

Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.

Bibliographical metadata

Original languageEnglish
Pages (from-to)10952-10957
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number27
DOIs
Publication statusPublished - 5 Jul 2011