Abstract
Neuroinflammation plays an important pathological role in experimental surgical brain injury (SBI). Apoptotic associated with phosphatidylserine (PS) externalization promotes anti-inflammatory mediator TGF-β1 release. In the present study, we investigated the anti-neuroinflammation effect of PS liposome or isoflurane pretreatment via PS/CD36/TGF-β1 signaling in a rat model of SBI. A total of 120 male Sprague-Dawley rats (weighing 280-330 gms) were used. SBI was induced by partial right frontal lobe corticotomy. Intranasal PS liposome or isoflurane inhalation was administered prior to SBI induction. CD36 small interfering RNA (siRNA) was administered intracerebroventricularly. Recombinant Annexin V protein (rAnnexin V) was delivered intranasally. Post-SBI assessments included neurological tests, brain water content, Western blot, and immunohistochemistry. Endogenous CD36 protein levels but not TGF-β1 was significantly increased within peri-resection brain tissues over 72 h after SBI. SBI rats were associated with increased brain water content surrounding corticotomy and neurological deficits. PS liposome pretreatment significantly reduced brain water content and improved some neurological deficits at 24 hours and 72 hours after SBI. PS liposome increased CD36 and TGF-β1 protein levels, but decreased IL-1β and TNFα protein levels in peri-resection brain tissues at 24 hours after SBI. CD36 siRNA or rAnnexin V partially countered the protective effect of PS liposome. Isoflurane pretreatment produced similar antineuroinflammation and neurological benefits in SBI rats partially by upregulating CD36/Lyn/TGF-β1 signaling. Collectively, our findings suggest that the activation of PS/CD36/TGF-β1 pathway by PS liposome or isoflurane prior to SBI could attenuate neuroinflammation and improve neurological outcomes in rats. PS liposome or isoflurane pretreatment may serve as an effective preventive strategy to minimize the brain injury caused by neurosurgical procedures in patients.
Highlights
Neurosurgical procedure itself has been shown to cause surgical brain injury (SBI) that contributes to the postoperative complications of brain edema, ischemia, and intracranial hematoma as well as neurological deficits [1, 2]
In experimental setting of SBI, neuroinflammation was characterized as microglial activation, peripheral immune cell infiltration, and increased proinflammatory cytokines within peri-resection brain tissues, which contributed to brain edema, brain tissue oxidative stress, and poor neurobehavioral
Western blot assay showed that brain CD36 protein levels were increased within peri-resection region at 1 day (p = 0:053) and 3 days (p = 0:051) after SBI (Figure 2(a))
Summary
Neurosurgical procedure itself has been shown to cause surgical brain injury (SBI) that contributes to the postoperative complications of brain edema, ischemia, and intracranial hematoma as well as neurological deficits [1, 2]. In experimental setting of SBI, neuroinflammation was characterized as microglial activation, peripheral immune cell infiltration, and increased proinflammatory cytokines within peri-resection brain tissues, which contributed to brain edema, brain tissue oxidative stress, and poor neurobehavioral. Apoptotic-associated PS receptor activation suppressed the elevation of proinflammatory mediators but induced antiinflammatory mediators release including TGF-β1 [9,10,11]. Administration of PS liposome 24 hours prior to and at the beginning of ischemia increased anti-inflammatory TGF-β1 level, suppressed the induction of proinflammatory markers, and promoted retinal neuron survival after ischemic injury [13]. Activation apoptotic mimicry phagocyte signaling may serve as a promising preventive neuroprotection strategy by creating an anti-inflammatory microenvironment against subsequent brain injury
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