Insulin-like growth factor 1 prevents neuronal cell death and paraplegia in the rabbit model of spinal cord ischemia

Objective: insulin-like growth factor 1 has been shown to be cytoprotective against ischemia-reperfusion injury in various organs. However, spinal cor d protection by insulin-like growth factor I has not been tested. We have t herefore examined the effect of insulin-like growth factor 1 on neuronal ce ll death and motor function after spinal cord ischemia. Methods: Japanese white rabbits were subjected to spinal cord ischemia by c lamping the abdominal aorta for 15 minutes. insulin-like growth factor 1 (0 .3 mg/kg) at a dose equipotent to insulin (0.3 IU/kg) in lowering blood glu cose lever or the control (phosphate-buffered saline solution as a vehicle) was administered intravenously 30 minutes before the aortic clamp. Results: Hind-limb motor function had recovered normally 48 hours after the operation in all the rabbits (n = 8) treated with insulin-like growth fact or i, In contrast, all the control-treated (n = 8) and all but one of the i nsulin-treated (n = 6) rabbits had deteriorated to paraplegia by 48 hours a fter the operation.. Histopathologic sections in the involved spinal cord s egment showed that a significantly (P < .0001) greater number of motor neur on cells were preserved in the rabbits treated with insulin-like growth fac tor 1 (17.9 +/- 4.8 per section) than in those treated with the control (8. 0 +/- 2.1). Although insulin was equipotent to insulin-like growth factor I in preserving the number of motor neuron cells (18.5 +/- 2.7), the percent age of motor neuron cells positive for terminal deoxynucleotidyltransferase -mediated deoxyuridine triphosphate-biotin nick-end labeling were significa ntly (P < .01) smaller in the rabbits treated with insulin-like growth fact or 1 (6.0 +/- 4.6) compared with those treated with the control (54.6 +/- 3 3,8) and insulin (26.2 +/- 11.7). Immunohistochemical studies revealed that insulin-like growth factor 1 increased expression of the antiapoptotic Bcl -xL protein and inhibited expression of the proapoptotic Bax protein in mot or neuron cells 24 and 48 hours after the operation. in contrast, expressio n of only Bar was increased after the operation in other groups of rabbits subjected to spinal cord ischemia, Conclusions: These results suggest that insulin-like growth factor i, but n ot insulin with a conventional dose, protects motor neuron cells from ische mic spinal cord injury associated with differential regulation of Bcl-xL an d Bar protein.