Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord.
The neuroprotective effects of insulin like growth factor-1 (IGF-1) on spinal cord injury induced edema formation, cell changes and profound upregulation of constitutive isoform of neuronal nitric oxide synthase (cNOS) was examined in a rat model. A focal spinal cord injury produced by making a lesion (about 2 mm deep and 5 mm long) of the right dorsal horn of the T10-11 segment resulted in a marked edema formation, cell injury and upregulation of cNOS following 5 h after trauma. In separate groups application of IGF-1 (0.1 microgram/microliter) topically on the exposed spinal cord (T10-11) starting from 30 min before injury (20 microliter), immediately before injury followed by 30 min, 60 min and thereafter every 1 h after injury until sacrifice resulted in significant attenuation of edema formation and cell changes. Immunohistochemistry showed a less pronounced expression of cNOS in the T9 and T12 segments of the cord in IGF treated rats compared to untreated traumatised controls. These results for the first time show that IGF treatment is neuroprotective and this effects of the IGF appears to be mediated via inhibition of NOS upregulation.
Sharma
H S
HS
Department of Anatoma, University Hospital, Uppsala University, Sweden.
Nyberg
F
F
Gordh
T
T
Alm
P
P
Westman
J
J
D000287:Administration, Topical; D000818:Animals; D004487:Edema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015854:Up-Regulation
D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat