Liposome-mediated NGF gene transfection following neuronal injury: potential therapeutic applications.

Abstract

We have systematically investigated the therapeutic potential of cationic liposome-mediated neurotrophic gene transfer for treatment of CNS injury. Following determination of optimal transfection conditions, we examined the effects of dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) liposome-mediated NGF cDNA transfection in injured and uninjured primary septo-hippocampal cell cultures and rat brains. In in vitro studies, we detected an increase of NGF mRNA in cultures 1 day after transfection. Subsequent ELISA and PC12 cell biological assays confirmed that cultured cells secreted soluble active NGF into the media from day 2 after gene transfection. Further experiments showed that such NGF gene transfection reduced the loss of chol- ine acetyltransferase (ChAT) activity in cultures following calcium-dependent depolarization injury. In in vivo studies, following intraventricular injections of NGF cDNA complexed with DC-Chol liposomes, ELISA detected nine- to 12-fold increases of NGF in rat CSF. Further studies showed that liposome/NGF cDNA complexes could attenuate the loss of cholinergic neuronal immunostaining in the rat septum after traumatic brain injury (TBI). Since deficits in cholinergic neurotransmission are a major consequence of TBI, our studies demonstrate for the first time that DC-Chol liposome-mediated NGF gene transfection may have therapeutic potential for treatment of brain injury.

• Authors: L L Zou, L Huang, R L Hayes, C Black, Y H Qiu, J R Perez-Polo, W Le, G L Clifton, K Yang
• Journal: Gene therapy (Gene Ther) Vol. 6 Issue 6 Pg. 994-1005 (Jun 1999) ISSN: 0969-7128 [Print] England
• PMID: 10455401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Liposomes
• Nerve Growth Factors
• Choline O-Acetyltransferase

Topics

• Animals
• Brain Injuries (enzymology, therapy)
• Cells, Cultured
• Choline O-Acetyltransferase (metabolism)
• Genetic Therapy (methods)
• Hippocampus
• Liposomes
• Nerve Growth Factors (genetics)
• Rats
• Rats, Sprague-Dawley
• Transfection (genetics)