513I schemic stroke is one of the leading causes of death and disability in the world, resulting from the disruption of blood supply to the brain. Intervention requires the restoration of blood flow, which can lead to reperfusion injury. Oxidative stress is thought to be the primary event during this process 1 because reperfusion stimulates an overproduction of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), which leads to the oxidation of proteins, lipids, and DNA and can induce cell proliferation, growth arrest, apoptosis, and necrosis.2 Meanwhile, the dysfunction of superoxide dismutase (SOD) and glutathione peroxidase can compromise endogenous antioxidant defense mechanisms and further exacerbate oxidative stress and ischemic/reperfusion (I/R) injury.3,4 Nuclear factor erythroid 2-related factor (Nrf)2 activates the transcription of antioxidant stress genes whose products act concertedly to remove ROS through sequential enzymatic reactions. 5 Studies have uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 is considered a valuable therapeutic target for free radical damage in brain after ischemia and reperfusion.MicroRNAs (miRs) are small (≈22 nt), noncoding, singlestranded RNA molecules that regulate gene expression at the posttranscriptional level by inhibiting translation or by cleaving RNA transcripts in a sequence-specific manner.6 MiR-424 is a tumor marker that is involved in cancer cell proliferation, Background and Purpose-We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury. Methods-Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H 2 O 2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated. Results-MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion.Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription fact...

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.