Abstract
ObjectiveBy exploring the effects of miR-29a-5p knockout on neurological damage after acute ischemic stroke, we aim to deepen understanding of the molecular mechanisms of post-ischemic injury and thus provide new ideas for the treatment of ischemic brain injury.MethodsmiR-29a-5p knockout rats and wild-type SD rats were subjected to transient middle cerebral artery occlusion (MCAO). miR-29a levels in plasma, cortex, and basal ganglia of ischemic rats, and in plasma and neutrophils of ischemic stroke patients, as well as hypoxic glial cells were detected by real-time PCR. The infarct volume was detected by TTC staining and the activation of astrocytes and microglia was detected by western blotting.ResultsThe expression of miR-29a-5p was decreased in parallel in blood and brain tissue of rat MCAO models. Besides, miR-29a-5p levels were reduced in the peripheral blood of acute stroke patients. Knockout of miR-29a enhanced infarct volume of the MCAO rat model, and miR-29a knockout showed M1 polarization of microglia in the MCAO rat brain. miR-29a knockout in rats after MCAO promoted astrocyte proliferation and increased glutamate release.ConclusionKnockout of miR-29a in rats promoted M1 microglial polarization and increased glutamate release, thereby aggravating neurological damage in experimental stroke rat models.
Highlights
Ischemic stroke is considered a disease that causes significant morbidity and mortality on a global scale
To determine the expression of miR-29a-5p in circulating blood and brain tissue, we examined miR-29a-5p level in the blood and brain tissue including basal ganglia and cortical following middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia of rats at 45 min, 24 h, and 7 days post-reperfusion
There was no significant difference of miR-29a-5p levels in the cortex area (Figure 2C), the expression of miR-29a5p was decreased in the brain tissue as well as circulating blood in rat MCAO models
Summary
Ischemic stroke is considered a disease that causes significant morbidity and mortality on a global scale. The first step in the inflammatory response in the brain is the activation and polarization of microglia, which in turn initiates the release of effector molecules and activation of other immune cells. M1 is activated through the classical pathway, expressing CD16 and iNOS on cell membranes, and secretes inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which exacerbate post-stroke brain injury (Iadecola and Anrather, 2012; Xiong et al, 2016; Kim and Bae, 2017). M2 is activated by an alternative pathway and expresses the characteristic markers CD206 and Arg on the cell membrane. It has a strong phagocytic ability and can engulf damaged nerve cells and tissue fragments to repair trauma and release some neuroprotective factors
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