Background-Stroke is a leading cause of death and disability worldwide; however, no effective treatment currently exists. Methods and Results-Rats receiving subcutaneous granulocyte colony-stimulating factor (G-CSF) showed less cerebral infarction, as evaluated by MRI, and improved motor performance after right middle cerebral artery ligation than vehicle-treated control rats. Subcutaneous administration of G-CSF enhanced the availability of circulating hematopoietic stem cells to the brain and their capacity for neurogenesis and angiogenesis in rats with cerebral ischemia. Conclusions-G-CSF induced increases in bone marrow cell mobilization and targeting to the brain, reducing the volume of cerebral infarction and improving neural plasticity and vascularization.

Aims Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. Methods and results CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Conclusions Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels.

Prion diseases are induced by pathologically misfolded prion protein (PrPSc ), which recruit normal sialoglycoprotein PrP C by a templatedirected process. In this study, we investigated the expression of PrP C in a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrP C -immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrP C protein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrP C protein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrP C by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrP C -Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrP C in the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrP C and activated extracellular signal-regulated kinase (ERK1/2) under hypoxia-reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia-reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrP C promoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3-to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrP C resulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrP C expression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrP C has physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

Transient receptor potential vanilloid type-1 (TRPV1) is a ligand-gated nonselective cation channel that has been well characterized in peripheral pain pathway. Recent evidence from animal models of temporal lobe epilepsy (TLE) has supported the important role of TRPV1 in epileptogenesis. In this study, we investigated the expression and cellular distribution of TRPV1 in the temporal cortex (CTX) and hippocampus (HPC) from 26 patients with mesial TLE (MTLE) compared with 12 histologically normal samples. Reverse transcription-PCR and Western blotting revealed up-regulated mRNA and protein levels of TRPV1 in the MTLE group versus the control group. Immunohistochemistry data demonstrated that TRPV1 was mainly distributed in the cell bodies and dendrites of neurons. Double-labeled immunofluorescence further revealed that TRPV1 was localized on NeuN-positive neurons and GFAP-positive astrocytes, but not on HLA-positive microglia. In addition, its co-localization with glutamate and gamma-aminobutyric acid (GABA) indicated that TRPV1 was distributed on both glutamatergic and GABAergic neurons. Moreover, nerve growth factor, a sensitizing factor for TRPV1, was showed a higher expression pattern in MTLE patients. Taken together, our findings suggest that the overexpression and distribution patterns of TRPV1 might be involved in the pathogenesis and epileptogenesis of human MTLE.