BackgroundEndothelin-1 (ET-1) is synthesized and upregulated in astrocytes under stroke. We previously demonstrated that transgenic mice over-expressing astrocytic ET-1 (GET-1) displayed more severe neurological deficits characterized by a larger infarct after transient middle cerebral artery occlusion (tMCAO). ET-1 is a known vasoconstrictor, mitogenic, and a survival factor. However, it is unclear whether the observed severe brain damage in GET-1 mice post stroke is due to ET-1 dysregulation of neurogenesis by altering the stem cell niche.MethodsNon-transgenic (Ntg) and GET-1 mice were subjected to tMCAO with 1 h occlusion followed by long-term reperfusion (from day 1 to day 28). Neurological function was assessed using a four-point scale method. Infarct area and volume were determined by 2,3,5-triphenyltetra-zolium chloride staining. Neural stem cell (NSC) proliferation and migration in subventricular zone (SVZ) were evaluated by immunofluorescence double labeling of bromodeoxyuridine (BrdU), Ki67 and Sox2, Nestin, and Doublecortin (DCX). NSC differentiation in SVZ was evaluated using the following immunofluorescence double immunostaining: BrdU and neuron-specific nuclear protein (NeuN), BrdU and glial fibrillary acidic protein (GFAP). Phospho-Stat3 (p-Stat3) expression detected by Western-blot and immunofluorescence staining.ResultsGET-1 mice displayed a more severe neurological deficit and larger infarct area after tMCAO injury. There was a significant increase of BrdU-labeled progenitor cell proliferation, which co-expressed with GFAP, at SVZ in the ipsilateral side of the GET-1 brain at 28 days after tMCAO. p-Stat3 expression was increased in both Ntg and GET-1 mice in the ischemia brain at 7 days after tMCAO. p-Stat3 expression was significantly upregulated in the ipsilateral side in the GET-1 brain than that in the Ntg brain at 7 days after tMCAO. Furthermore, GET-1 mice treated with AG490 (a JAK2/Stat3 inhibitor) sh owed a significant reduction in neurological deficit along with reduced infarct area and dwarfed astrocytic differentiation in the ipsilateral brain after tMCAO.ConclusionsThe data indicate that astrocytic endothelin-1 overexpression promotes progenitor stem cell proliferation and astr ocytic differentiation via the Jak2/Stat3 pathway.

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Medical students' motivation and study strategies are crucial in determining academic performance. This study aimed to assess the motivation and learning strategies of medical students as well as their association with performance in anatomy examinations. The Motivated Strategies for Learning Questionnaire, two focus group discussions, and students' current anatomy cumulative grade point average (cGPA) were used. Generally, the medical students strongly felt that anatomy is fundamental to the practice of medicine and surgery. This result was consistent with high task value scores of 5.99 ± 1.25. They were also driven by extrinsic goal orientation (5.59 ± 1.42) and intrinsic goal orientation (5.08 ± 1.26). Most medical students typically relied on elaboration (5.35 ± 1.25) ahead of other cognitive strategies namely rehearsal (5.30 ± 1.11), organization (5.15 ± 1.34), and lowest‐rated critical thinking (4.77 ± 1.19). The students also relied on resource management strategies, effort regulation (5.15 ± 1.20) and time and study environment regulation (5.03 ± 1.03) more than the moderately scored peer learning (4.95 ± 1.50) and help‐seeking (4.95 ± 1.09). In the focus group discussions, students reported that they often narrate or explain to each other what they would have read and understood from anatomy lectures, tutorials, and textbooks. They also bemoaned the lack of institutional support for stress burdens. The motivation and learning strategies subscales were not correlated with anatomy cGPA. Males were driven by extrinsic goals and experienced significantly higher levels of test anxiety than females (P < 0.05). Knowing the motivation and learning strategies students employ early in the medical curriculum can be leveraged to promote self‐directed learning and academic achievement.