Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

Abstract

BACKGROUND:Recent studies have showed that S100A8 has been implicated in the pathobiology of inflammatory disorders, and that cerebral ischemia reperfusion (I/R) rapidly activates inflammation responses via Toll-like receptor 4 (TLR4). This study aimed to explore the expression of S100A8 and the relationship between S100A8 and TLR4 in focal cerebral ischemia reperfusion injury.METHODS:C3H/HeJ mice (n=30) and C3H/HeN mice (n=30) were divided randomly into a C3H/HeJ model group (n=18), a C3H/HeJ control group (n=12), a C3H/HeN model group (n=18), and a C3H/HeN control group (n=12). Middle cerebral artery I/R model in mice was produced using a thread embolism method. The brains of the mice were collected after ischemia for 1 hour and reperfusion for 12 hours. Stroke outcome was evaluated by determination of infarct volume and assessment of neurological impairment scores. Brain injury after cerebral I/R was observed by an optical microscope after TTC and HE dyeing. The immunofluorescence technique and real time PCR were used to test the expression level of S100A8 in brain damage.RESULTS:Compared with C3H/HeN mice, TLR4-deficient mice (C3H/HeJ) had lower infarct volumes and better outcomes in neurological tests. The levels of S100A8 increased sharply in the brains of mice after I/R injury. In addition, mice that lacked TLR4 (C3H/HeJ) had lower expression of I/R-induced S100A8 than C3H/HeN mice in the model group, indicating that a close relationship might exist between the levels of S100A8 and TLR4.CONCLUSION:S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by I/R injury.

Plasma Calprotectin Is Predictive for Short-Term Functional Outcomes of Acute Ischemic Stroke

“…These lines of evidence imply that calprotectin might play a pivotal role in the pathogenesis of cardiovascular diseases. Although previous animal studies have demonstrated that calprotectin could promote neuroinflammation and exacerbate the pathology of AIS ( 20 ), limited evidence is available in human studies, with only two studies investigated the association between calprotectin and prognosis of stroke ( 21 , 22 ). Specifically, Guo et al investigated the association between baseline calprotectin levels and 3-month functional outcomes of AIS.…”

S100a8 silencing attenuates inflammation, oxidative stress and apoptosis in BV2 cells induced by oxygen‑glucose deprivation and reoxygenation by upregulating GAB1 expression

“…Previous studies have highlighted the importance of S100a8 in the pathobiology of inflammatory disorders ( 11 , 37 , 38 ). Treatment with S100a8/a9 has been demonstrated to markedly increase the secretion of the aforementioned pro-inflammatory cytokines in cultured BV2 microglial cells ( 14 ). Notably, S100A8 induces cytokine expression via the ROS-dependent activation of NF-κB ( 39 ).…”

“…It is well known that S100a8 is involved in the pathobiology of inflammatory disorders ( 13 ). S100a8 is highly expressed in the brains of mice following focal cerebral I/R injury ( 14 ). Increasing evidence suggests that S100a8/a9 genes are significantly upregulated during the early stages of myocardial I/R injury ( 15 , 16 ).…”

Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia‐reperfusion injury

“…Neurologic outcomes were graded as: 0, normal; 1, forepaw monoparesis; 2, circling to right; 3, falling to right; and 4, no spontaneous walking and depressed consciousness (45). The brain was cut into 2 mm thick coronal blocks and stained in the dark with 2, 3, 5‐triphenyltetrazolium chloride for 1 h at 37°C, and the infarct volume was calculated (46). Where indicated, 1 μg/kg (18 nmol/kg) sTM or an equimolar dose of scFv/TM was injected into the right jugular vein 20 min before MCA occlusion.…”