Potentiation of spinal cord conduction and neuroprotection following nanodelivery of DL-3-n-butylphthalide in titanium implanted nanomaterial in a focal spinal cord injury induced functional outcome, blood-spinal cord barrier breakdown and edema formation

Int Rev Neurobiol. 2019:146:153-188. doi: 10.1016/bs.irn.2019.06.009. Epub 2019 Jul 8.

Abstract

Spinal cord injury (SCI) is a devastating disease inflicting lifetime disability to the victims. Military personnel are quite often victims of SCI for which no suitable therapeutic strategies have been developed so far. The main reason for SCI induced disability is loss of neural connections below and above the lesion site causing motor paralysis and somatosensory disturbances Loss of neuronal connections thwart spinal cord conduction resulting in motor function disability. To enhance spinal cord conduction grafting of peripheral nerves, implant of hydrogels filled with neuroprotective drugs is used but so far, no satisfactory results re achieved. In this regards implants of microelectrode for enhancing tissue connectivity is suggested that is still under experimental state. We have used titanium implant with or without TiO2 nanowires in a focal spinal cord injury and studies spinal cord pathology and motor function. In addition, we also combined with nanowired delivery of a potential neuroprotective drug DL-3-n-butylphthalide (DL-NBP) to the spinal cord in a rat model. Our observations show that a combination of titanium implant with nanowired delivery of DL-NBP induces superior neuroprotection and enhance motor functions after SCI. This treatment also restored blood-spinal cord barrier (BSCB) function and reduces edema formation and cell injury after SCI, not reports earlier.

Keywords: Blood-spinal cord barrier; DL-3-n-butylphthalide; Nanowired delivery; Neuroprotection; Spinal cord edema; Spinal cord injury; Titanium implant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzofurans / pharmacology*
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Drug Delivery Systems / methods
  • Drug Implants / pharmacology
  • Edema / physiopathology*
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Locomotion / physiology*
  • Male
  • Nanostructures / chemistry
  • Nanowires / chemistry
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / prevention & control*
  • Titanium / chemistry
  • Titanium / pharmacology*

Substances

  • Benzofurans
  • Drug Implants
  • Neuroprotective Agents
  • 3-n-butylphthalide
  • Titanium