Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell mitogen that has been shown to induce vasculogenesis and angiogenesis in many organ systems and tumors. Considering the importance of VEGF to embryonic vascularization and survival, the effects of administered VEGF on developing or adult cerebrovasculature are unknown: can VEGF alter brain angiogenesis or mature cerebrovascular patterns? To examine these questions we exposed fetal, newborn, and adult rat cortical slice explants to graduated doses of recombinant VEGF. The effects of another known angiogenic factor, basic fibroblast growth factor (bFGF), were evaluated in a comparable manner. In addition, we infused VEGF via minipump into the adult cortex. Significant angiogenic effects were found in all VEGF experiments in a dose-responsive manner that were abolished by the addition of VEGF neutralizing antibody. Fetal and newborn explants had a highly complex network of branched vessels that immunoexpressed the flt-1 VEGF receptor, and flk-1 VEGF receptor expression was determined by reverse transcription–PCR. Adult explants had enlarged, dilated vessels that appeared to be an expansion of the existing network. All bFGF-treated explants had substantially fewer vascular profiles. VEGF infusions produced both a remarkable localized neovascularization and, unexpectedly, the expression of flt-1 on reactive astrocytes but not on endothelial cells. The preponderance of neovascularization in vitro and in vivo, however, lacked the blood–brain barrier (BBB) phenotype marker, GLUT-1, suggesting that in brain the angiogenic role of VEGF may differ from a potential BBB functional role, i.e., transport and permeability. VEGF may serve an important capacity in neovascularization or BBB alterations after brain injury

Design of an Online Histology and Pathology Atlas for Medical Students: an Instructional Aid to Self-Directed Learning

© 2017, International Association of Medical Science Educators. Background: Several institutions have integrated histology with other disciplines in team-based laboratory designs, but the integration of histology and pathology instructional tools for medical student learning has been less commonly reported in the literature compared to other basic sciences. Objective: The primary aim of this study was to develop and pilot an on-line and accessible atlas of histology and histopathology, the Microanatomy and Pathology Atlas (MAPA), for use by medical students as an adjunct to learning histology and pathology in a medical school curriculum. The design of MAPA is based on the theoretical framework of adult learning theory and Gagne’s theory of learning as applied to instructional design. Student evaluations of MAPA as an instructional resource tested the hypothesis that the Atlas would be self-selected by students and that students would find it a satisfactory and valuable asset to their learning. Method: MAPA was developed by a multidisciplinary team at The George Washington University School of Medicine and Health Sciences (GWU-SMHS). The Atlas includes a library of histology and histopathology images. Images in the Atlas illustrate key features of histology and pathology that are present in the associated digital slides assigned for student learning. Traditional laboratory manual instructions and study objectives are linked to specific interactive online-labeled images that allow for self-testing, and all of the pathology slides are embedded in clinical case studies that give the pathology real-world context. A mixed method design was used to evaluate data collected in 2015 on the frequency and usage of MAPA by medical students in the preclinical years, using a modified four-point Likert-style survey and open-ended questions to capture student satisfaction and perceived learning. Results: Survey results demonstrated that in students’ opinions, MAPA is a useful too, complemented their other teaching courses, and it was set at a difficulty level that they felt was appropriate. About 92% of students indicated they would use the tool again in the future. Conclusion: MAPA has been successfully implemented as an instructional tool for medical student learning of histology and histopathology and has been perceived by medical students as a helpful, web-based, and self-selected adjunct for learning. The results suggest that MAPA and similar web-based learning tools can be used to encourage and support self-directed medical student learning in histology and pathology and suggests that similar instructional tools may be useful in other disciplines to promote more active student learning