EFFECT OF PROPOFOL ON AUTOPHAGY - MEDIATED STRESS RESPONSE IN MOTOR NEURON AFTER TRANSIENT SPINAL CORD ISCHEMIA IN RABBITS
Y. Watanabe1, M. Sakurai2, T. Kawamura1, K. Abe3
Anesthesiolosy, Cardiovascular Surgery, National Hospital Organization Sendai Medical
Center, Sendai, Neurology, Okayama University, Okayama, Japan
Objective: The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. The aim of this study was to investigate whether propofol could protect against ischemic spinal cord damage by suppressing autophagic change.
Methods: We used a rabbit spinal cord ischemia model with use of a balloon catheter. In transient ischemia and treatment with vehicle group and treatment with propofol group, saline or propofol was administered intravenously 10 minutes before the induction of ischemia. Spinal cord was removed at 8 hours, and 1, 2, and 7 days after 15 minutes of transient ischemia. Cell damage was analyzed by counting the number of motor neurons and histological changes. Western blot analysis used for microtubule-associated protein light chain 3(LC3) andγ-aminobutyric-acid type-A (GABAA) -receptor-associated protein (GABARAP), temporal profiles of LC3 and GABARAP immunoreactivity were performed.
Results: In the Group I, about 85% of motor neurons were preserved until 2 days after reperfusion, but were serectively lost at 7 days. In contrast, in the Group P, motor neurons were presereved after 2 days. Western blot analysis and immunoreactivity for LC3 and GABARAP demonstrated that the induction of LC3 and GABARAP were slightly detectable in the sham group samples, which was then strongly enhanced at 8 hours, and was preserved until 2 days after reperfusion in the Group I. In the group P, LC3 and GABARAP were detectable but did not
admit enhancement.
Conclusions: Propofol eased the functional deficits and increased the number of motor neuons after ischemia. This study indicates that propofol may protect motor neurons from ischemic injury by suppressing augtophagic change. These results suggest that Propofol is a therapeutic agent in the treatment of ischemic spinal cord injury.