The purpose of this work is to repeatedly introduce exogenous macrophages (M theta), activated to their secretory state, into rats with a spinal cord injury. The exogenous M theta provide a continual supply of vasogenic and growth factors that might promote regeneration of axons across the lesion. Previously, we showed that exogenous M theta can be introduced into the medulla of a brain upon which is placed a muscle autograft. We now ask whether the introduction of such exogenous, activated M theta and, eventually of monocytes, can promote regeneration of damaged central axons. A crush lesion is made epidurally at the T-5 segment of the spinal cord in adult rats. M theta, activated with lipopolysaccharide to their secretory state when they release their vasogenic and growth factors, are injected intraperitoneally at different times over a 3-week period following the injury. The exogenous, activated M theta, in this preliminary work, are attracted to and accumulate at the injured site. In those rats that had received the M theta 24 hr after injury and repeatedly thereafter, cavitation of the cord was less and the cellular density around the lesion was greater than in untreated rats. Monocytes which survive longer in vivo than do activated M theta, and whose functional states are more readily recognizable, are to be used next.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002869-01
Application #
3846345
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code