Single Injections of a DNA Plasmid That Contains the Human Bcl-2 Gene Prevent Loss and Atrophy of Distinct Neuronal Populations after Spinal Cord Injury in Adult Rats

Abstract

Spinal cord injury in adult mammals causes atrophy or loss of axotomized neurons. We have previously found that the product of the antiapoptotic gene Bcl-2, delivered by intraspinal injection of a DNA plasmid, reduces atrophy and loss of axotomized Clarke's nucleus neurons in adult rats. Here we studied whether the same treatment protects axotomized red nucleus (RN) neurons. Two months after the right dorsolateral funiculus was ablated in adult Sprague-Dawley rats by C3/C4 subtotal hemisection, there was approximately 48% loss of RN neurons in the magnocellular portion of the RN contralateral to the lesion and atrophy of many surviving neurons. When a DNA plasmid encoding the human Bcl-2 gene and the bacterial reporter gene LacZ, complexed with cationic lipids, was injected just rostral to the subtotal hemisection site, 87% of RN neurons survived, and there was partial, but robust, protection from atrophy. These and our previous results indicated that intraspinal administration of the Bcl-2 gene can prevent retrograde cell loss and reduce atrophy of axotomized RN and Clarke's nucleus neurons in adult rats and provide an effective means to rescue neurons whose survival depends on different growth factors.