Previous studies have shown that xenon-delayed postconditioning for up to 2h after
reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury
in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase
(PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection.
The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group,
2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2
group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group,
7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group,
and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was
induced for 25min in male Sprague-Dawley rats. Neurological function was assessed
using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12,
24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was
performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion.
Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal
cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all
rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic
neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with
the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal
motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and
p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe
and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and
p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning
improves neurological outcomes to spinal cord I/R injury in rats through the activation
of the AKT and ERK signaling pathways.