Repeated topical application of growth hormone attenuates blood-spinal cord barrier permeability and edema formation following spinal cord injury: an experimental study in the rat using Evans blue, ([125])I-sodium and lanthanum tracers.
The neuroprotective efficacy of growth hormone on a focal spinal cord trauma induced alteration in the blood-spinal cord barrier (BSCB) and edema formation was examined in a rat model. Under Equithesin anaesthesia, one segment laminectomy was done over the T10-11 segments. Spinal cord injury was produced by making an incision into the right dorsal horn of the T10-11 segments (2 mm deep and 4 mm long). The animals were allowed to survive 5 h after injury. Highly purified rat growth hormone [rGH, 25 microl of a 1microg/ml solution) was applied over 10 sec topically on the exposed surface of the spinal cord 30 min before injury. The identical doses of the rGH were repeated 0 min, 30 min, 60 min, 120 min, 180 min and 240 min following injury. Saline (0.9% NaCl) treated traumatised rats at identical intervals served as controls. Traumatised rats treated with saline exhibited marked edema formation and extravasation of Evans blue and ([125])Iodine tracers in the spinal cord. At the ultrastructural level, perivascular edema and exudation of lanthanum across the endothelial cells was quite frequent in the spinal cord. Pretreatment with rGH significantly attenuated the edema formation and the extravasation of tracers in the spinal cord. In these rats, perivascular edema and infiltration of lanthanum across the endothelial cells was not much evident. These observations show that the rGH has the capacity to reduce the early manifestations of microvascular permeability disturbances and edema formation following trauma and further suggest a possible therapeutic potential of the hormone for the treatment of spinal cord injuries.
Nyberg
F
F
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. Fred.Nyberg@farmbio.uu.se
Sharma
H S
HS
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D004396:Coloring Agents / Q000378:metabolism; D004487:Edema / Q000188:drug therapy*; D005070:Evans Blue / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000378:metabolism; D007796:Laminectomy; D007811:Lanthanum / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
D004396:Coloring Agents; D007457:Iodine Radioisotopes; D018696:Neuroprotective Agents; D005070:Evans Blue; D007811:Lanthanum; D013006:Growth Hormone; D012964:Sodium