Nonviral gene transfer of hepatocyte growth factor attenuates neurologic injury after spinal cord ischemia in rabbits.
OBJECTIVE
Paraplegia caused by spinal cord ischemia remains a serious complication after surgical repair of thoracoabdminal aortic aneurysms. Hepatocyte growth factor is a potent angiogenic and neurotrophic factor. We sought to investigate the neuroprotective effect of gene transfer of hepatocyte growth factor on spinal cord ischemia in rabbits.


METHODS
Human hepatocyte growth factor expression plasmid was combined with hemagglutinating virus of Japan envelope vector. Hemagglutinating virus of Japan envelope vector containing the hepatocyte growth factor gene was injected intrathecally into the experimental rabbits, whereas control vector or saline was given to the control animals. Five days later, spinal cord ischemia was induced by means of infrarenal aortic occlusion for 30 minutes. Hind-limb motor function was assessed during a 14-day recovery period with Tarlov criteria.


RESULTS
Human hepatocyte growth factor was detected in the cerebrospinal fluid 3 days after gene transfer, and the level peaked on day 5. Compared with the control animals, hepatocyte growth factor gene transfer significantly increased the capillary density in the gray matter and decreased the spinal cord edema. All rabbits pretreated with saline or control vector had hind-limb paraplegia (Tarlov score = 0) 14 days after spinal cord ischemia. However, previous transfection of the hepatocyte growth factor gene remarkably enhanced the Tarlov scores, and 8 of the 9 rabbits showed normal motor function (Tarlov score = 5) after a 14-day recovery period. Histologic examination showed that the intact motor neurons were preserved to a much greater extent in the rabbits transfected with the hepatocyte growth factor gene.


CONCLUSIONS
Gene transfer of hepatocyte growth factor attenuates neurologic injury after spinal cord ischemia.
Shi
Enyi
E
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. tkazui@hama-med.ac.jp
Jiang
Xiaojing
X
Kazui
Teruhisa
T
Washiyama
Naoki
N
Yamashita
Katsushi
K
Terada
Hitoshi
H
Bashar
Abul Hasan Muhammad
AH
D000818:Animals; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D010264:Paraplegia / Q000209:etiology* / Q000517:prevention & control*; D011817:Rabbits; D020760:Spinal Cord Ischemia / Q000150:complications* / Q000628:therapy*
D017228:Hepatocyte Growth Factor