Low molecular weight compounds with affinity to melanocortin receptors exert neuroprotection in spinal cord injury--an experimental study in the rat.
The possibility that five new low molecular weight compounds with varying affinity and selectivity to the melanocortin receptors will exert neuroprotective effects in the spinal cord injury (SCI) induced edema formation and cell damage was examined in a rat model. A focal trauma of the rat spinal cord made by an incision into the right dorsal horn (T10-11) resulted in profound edema formation, leakage of Evans blue albumin and cell injury of the T9 segment at 5 h. Topical application of the Melacure compound ME10501 in high doses (10 microg in 10 microl) given 5 min after SCI resulted in most significant neuroprotection of the T9 segment of the cord compared to other compounds. Thus, marked reduction in water content, leakage of Evans blue albumin, and cell injury were observed in ME10501 treated traumatised rats. These observations suggest that the non-peptide compound ME10501 with affinity to the melanocortin receptor MC4 is capable to induce neuroprotection in the spinal cord following trauma not reported earlier.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Lundstedt
T
T
Flärdh
M
M
Westman
J
J
Post
C
C
Skottner
A
A
D000818:Animals; D001667:Binding, Competitive; D001834:Body Water / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000209:etiology; D008297:Male; D008970:Molecular Weight; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044101:Receptors, Melanocortin / Q000378:metabolism*; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000209:etiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology*
D018696:Neuroprotective Agents; D044101:Receptors, Melanocortin