A Long-term Neuroprotective Effect Of Sevoflurane Postconditioning On Traumatic Brain Injury In Rats And The Role Of PI3K/Akt Pathway

Objective:It needs very careful consideration that what anesthetic agents would choose for patients with traumatic brain injury. Sevoflurane could provide fast induction and revival due to its low blood gas partition coefficient and lower the cerebral metabolic rate for oxygen, so it is an ideal drug for neurosurgery. Studies showed that sevoflurane postconditioning could provide acute neuroprotection, and the phosphoinositide 3-kinase/Akt pathway takes part in the modulation of the neuronal apotosis, but it's still unknown whether this neuroprotective effect could be sustained and if the phosphoinositide 3-kinase/Akt pathway is involved in. We use a fluid percussion traumatic brain injury model in rat to investigate the long-term neuroprotective effect of sevoflurane postconditioning and the influence on the expression of Akt, to see if it has protective effect on traumatic brain injury and the probable mechanism, to provide theoretical basis for clinical application.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups.â‘ the sham group [Sham], do sham operation to the rats, just cut the scalp and perforate the skull, then put into a chamber for oxygen inhalation for 1 h.â‘¡the traumatic brain injury group [TBI], do trauma to the brain and then the rats were put into a chamber for oxygen inhalation for 1 h.â‘¢the sevoflurane postconditioning group [TBI+SP], after the trauma the rats were put into a chamber for 3% sevoflurane inhalation for 1 h. The traumatic brain injury model was induced by a fluid percussion device. After traumatic brain injury or sham surgery rats were placed in a chamber and treated with sevoflurane or O2 (3% sevoflurane,4 L/min O2) for 1 h. Apoptosis were studied 24 h after by TUNEL assay, the neurological impairement was measured by the modified neurological severity score system, spatial learning and memory was examined by Morris water maze test and the expression of phosphorylated Akt in the brain after sevoflurane administration were analyzed by western blot method.Results:As compared with the TBI group, the number of TUNEL positive neurons was significantly decreased in the TBI+SP group at 24 h after traumatic brain injury (P<0.05), Sham group showed few apototic neurons (P<0.01). At day 1,7 and 21, the neurological severity score scores in the TBI+SP group were lower than the TBI group (P<0.05), and significantly lowered at day 14 and 28 (P<0.01); the neurological severity score scores in TBI and TBI+SP group were much higher compared with Sham group (P<0.01). The escape latency which measures cognitive function was significantly shorter in the TBI+SP group than the TBI group during the two testing periods (period 1:P<0.05, period 2:P<0.01), but significantly prolonged in the TBI group compared to the Sham group (P<0.01). The rats in the TBI+SP group spent more time in the target quadrant than the TBI group at day 27 after traumatic brain injury (P<0.05), but significantly decreased in the TBI group compared to the Sham group (13 d: P<0.05,27 d:P<0.01), there is no significant statistical difference between the TBI+SP and Sham group (P>0.05). The percentage of phosphorylated Akt/Akt were significantly higher in TBI group than Sham group at 7,14 posttraumatic days (7 d:P<0.01,14 d:P<0.05), but there is no significant difference at 28 d (P>0.05), it also significantly increased in the TBI+SP group than group Sham and T at 7,14 and 28 d (vs S:P<0.01; vs T:7 d; P<0.05; vs T:14,28 d, P<0.01).Conclusion:During the study lasting for 28 days, the data suggest that postconditioning with sevoflurane after TBI could inhibit the apoptosis of neurons to promote neuronal survival and improve neurological function and behavior performance to alleviate cognitive deficits induced by brain trauma, so it has long-term neuroprotective effect and this effect can sustain for at least 28 days. We also found that the phosphoinositide 3-kinase/Akt pathway is associated with this neuroprotective effect. The phosphoinositide 3-kinase/Akt pathway plays a role in the traumatic brain injury and takes part in the protective effect of sevoflurane postconditioning on traumatic brain injury.