Abstract WMP79: Phosphatidylserine-containing Liposomes Pretreatment Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury

Abstract

Introduction: Surgical brain injury (SBI), exclusively attributable to the neurosurgical procedure itself may cause postoperative complications. Neuroinflammation plays an important patholgoical role in the setting of SBI. Previous study demonstrated that the phosphatidylserine-containing liposomes (PS) pretreatment promoted ischemic retinal neuron survival by suppressing pro-inflammatory markers. In the present study, we investigated the anti-neuroinflammation effects of PS pretreatment in a rat model of SBI. Methods: Total of 60 adult male Sprague-Dawley rats were used in the following groups of Sham (n=18), SBI+vehicle (n=18), SBI+PS 0.17mg (n=6) and SBI+PS 0.5mg (n=18). SBI rats were subjected to partial right frontal lobe corticotomy. Shams were subjected to the same surgical procedure without undergoing corticotomy. Phosphatidylserine-containing liposomes (PS) or phosphatidylcholine-containing liposomes (PC, as vehicle control) were administered via intranasal route at 24h and 1h in prior to SBI induction. Outcomes assessments included 1) modified Garcia neurobehavioral test and brain water content at 24h and 72h post-SBI; and 2) western blot for pro/anti-inflammatory cytokines at 24h post-SBI. Results: All the rats survived except that 3 SBI rats died within 24h post-surgery. PS pretreatment at dose of 0.5mg significantly reduced peri-resection brain water content and improved neurological deficits associated with SBI at 24h and 72h post-injury (Fig.1). Consistently, western blot showed that there were less pro-inflammatory cytokines, but higher level of anti-inflammatory cytokine TGF-β1 within peri-resection brain regions of PS pretreated rats at 24h post-SBI. Conclusion: Our findings suggest that phosphatidylserine-containing liposomes may be a novel approach to ameliorate SBI by its anti-inflammation effects.