MiR-10b-3p alleviates cerebral ischemia/reperfusion injury by targeting Krüppel-like factor 5 (KLF5).

Although miR-10b-3p has been identified to be involved in cerebral ischemia injury, its impact and specific mechanism in cerebral ischemia injury remain unclear. The effects of Mir-10b-3p were investigated by establishing rat and cell models of ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGD/R) was performed on pheochromocytoma-12 (PC12) cells. MiR-10b-3p expression levels in brain tissues and PC12 cells were detected by qRT-PCR. The impacts of miR-10b-3p on neurological deficits, infarct volume, inflammatory factor expression, in vivo brain water content, cell viability, and cell apoptosis were assessed. The relationship between miR-10b-3p and KLF5 was determined by TargetScan and luciferase reporter assay. The rescue experiments were performed to confirm the role of this axis in cerebral ischemia injury. Mir-10b-3p levels in rat brain tissue and PC12 cells were significantly decreased after I/R injury. MiR-10b-3p overexpression obviously reduced neurological deficits, infarct volume, brain water content, inflammatory factors expression, and neuronal apoptosis in the brain of ischemia-stroked rats. Meanwhile, miR-10b-3p upregulation also inhibited cell viability and apoptosis of OGD/R-induced PC12 cells. Besides, KLF5 was identified as a target of miR-10b-3p, and rescue experiments revealed that KLF5 was involved in the regulation of miR-10b-3p in ischemic injury. Our results demonstrated that miR-10b-3p had the neuroprotective effects against ischemia injury by targeting KLF5 and provided a potential underlying target for ischemic stroke treatment.

Dexmedetomidine exerts a protective effect on ischemic brain injury by inhibiting the P2X7R/NLRP3/Caspase-1 signaling pathway.

Dexmedetomidine (Dex) has been suggested to exert a protective function in ischemic brain injury. In this study, we aimed to elucidate the intrinsic mechanisms of Dex in regulating microglia pyroptosis in ischemic brain injury via the purinergic 2X7 receptor (P2X7R)/NLRP3/Caspase-1 signaling pathway. First, permanent middle cerebral artery occlusion (p-MCAO) rat model was established, followed by the measurement of behavioral deficit, neuronal injury, the volume of brain edema and the infarct size. Dex treatment was suggested to alleviate the neurological deficits in p-MCAO rats and reduce the brain water content and infarct size. Additionally, rat microglia were cultured in vitro and a model of oxygen and glucose (OGD) was established. Microglia cell activity and ultrastructure were detected. Dex could increase cell activity and reduce LDH activity, partially reversing the changes in cell morphology. Furthermore, the activation of P2X7R/NLRP3/Caspase-1 pathway was tested. The obtained findings indicated Dex suppressed microglial pyroptosis by inhibiting the P2X7R/NLRP3/Caspase-1 pathway. Inhibition of P2X7R or NLRP3 could inhibit Caspase-1 p10 expression, improve cell activity, and reduce LDH activity. The same result was verified in vivo experiments. This study indicated that Dex inhibited microglia pyroptosis by blocking the P2X7R/NLRP3/Caspase-1 pathway, thus playing a protective role against ischemic brain injury.

Intracranial High-Grade Stenosis and Hyperhomocysteinemia Presenting as Cortical Subarachnoid Hemorrhage Concomitant with Acute Ischemic Stroke in a Young Man.

BACKGROUND Cortical subarachnoid hemorrhage (cSAH) is a rare clinical presentation with different causes, but rarely happens along with acute ischemic stroke. Intracranial high-grade stenosis originated from brain has been regarded as an unusual cause of cSAH, especially in young adults. CASE REPORT A case of 33-year-old male presented with mild headache and spontaneous left-sided body weakness. Initial brain computed tomography (CT) showed cSAH in the right superior frontal sulcus. Further neuroimaging examinations including magnetic resonance imaging (MRI), digital subtraction angiography (DSA), transesophageal echocardiogram (TEE); in addition, lumbar puncture and blood tests were performed. Diffusion-weighted imaging (DWI) showed an acute infarction in the right frontal lobe and corona radiata of the territory of middle cerebral artery (MCA). The MR angiography (MRA) displayed no flow signal in the right middle cerebral artery M1-segment, while the DSA displayed bloodstream slowness in the right MCA M1-segment which suggested high-grade stenosis of the right MCA. The abnormal laboratory data suggested hyperhomocysteinemia, and excluded causes of thrombosis, infection, or cancer. The mechanism of cSAH may come about in severe atherosclerotic stenosis of MCAs by the broken of expanded tenuous compensatory pial vessels. The patient had good recovered at follow-up. CONCLUSIONS This case demonstrates cSAH with acute ischemic stroke, which is an uncommon complication, in a young adult stroke patient; a high-grade atherosclerotic stenosis of the MCA was identified as the etiology.