Design for learning: adapting the microscopic anatomy laboratory to adult learners.

Medical school curricula are undergoing transformational change in response to calls for integrating content across courses and years to enable better retention and application and for individualizing learning to meet the diverse backgrounds and thus differing needs of students. To address the related teaching challenges, faculty can employ solid principles of adult learning and instructional design and use teaching strategies that stimulate different learning styles. We developed laboratory sessions that follow a learner-centered instructional design model we refer to as "PLHET," reflecting the steps of preparing, linking, hooking, engaging, and transferring learning, and also applied teaching strategies that reflect Kolb's four styles of learning (accommodative, divergent, assimilative, and convergent).

VEGF in the nervous system.

Vascular endothelial growth factor (VEGF, VEGFA) is critical for blood vessel growth in the developing and adult nervous system of vertebrates. Several recent studies demonstrate that VEGF also promotes neurogenesis, neuronal patterning, neuroprotection and glial growth. For example, VEGF treatment of cultured neurons enhances survival and neurite growth independently of blood vessels.

Vascular endothelial growth factor enhances migration of astroglial cells in subventricular zone neurosphere cultures.

Vascular endothelial growth factor (VEGF) is an endothelial and neuronal survival factor and a mitogen for endothelial cells and astrocytes in both explant and in vivo injury models. In the CNS, interplay between the vasculature and neural stem progenitor (NSP) cells is required for the maintenance of angiogenic/neurogenic coordination in the germinal niche in the subventricular zone (SVZ) of the lateral ventricle. Using an in vitro SVZ neurosphere (NS) model, this study aimed to understand the direct effects of VEGF and its receptor signaling on neonatal NSP cell growth and migration.

Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury.

Following trauma to the brain significant changes occur in both the astroglial and vascular components of the neuropil. Angiogenesis is required to re-establish metabolic support and astrocyte activation encompasses several functions including scar formation and the production of growth factors. VEGF has seminal involvement in the process of brain repair and is upregulated during many pathological events.

Astrocyte growth effects of vascular endothelial growth factor (VEGF) application to perinatal neocortical explants: receptor mediation and signal transduction pathways.

The non-angiogenic role of vascular endothelial growth factor (VEGF), and its receptors flt-1 and flk-1, together with downstream signaling pathways were examined in fetal and postnatal rat cerebral cortical organotypic explants. VEGF application in both paradigms caused a significant increase in astroglial proliferation and a dose-dependent increase in GFAP and nestin immunoreactivity. The VEGF receptor flt-1 was observed on most, though not all astrocytes, while flk-1 receptor immunoexpression was absent.

New roles for VEGF in nervous tissue--beyond blood vessels.

Vascular endothelial growth factor (VEGF) is a secreted dimeric polypeptide that until recently has been believed to be a specific mitogen for endothelial cells subserving angiogenesis and permeability in development and after injury. Recent studies have depicted the localization of VEGF and its receptors on neurons and astrocytes and it has been shown to induce neuritic growth and to provide neuroprotection particularly after ischemia or spinal cord injuries. VEGF also shares common receptor signaling with the guidance molecule SEMA3A and thus could have an additional role linking the coordinated patterning of developing vascular and nervous tissue.

Vascular endothelial growth factor promotes neurite maturation in primary CNS neuronal cultures.

Recent studies have demonstrated that vascular endothelial growth factor (VEGF) and its receptor VEGFR2 (flk-1) are expressed by neurons during development and following hypoxic-ischemic events. Moreover, fetal CNS tissue explants exposed to exogenous VEGF exhibit increased neuronal Map-2 expression, suggesting that VEGF could have an effect on neuronal maturation. To determine whether this effect is of a direct nature, we examined the expression of Map-2 in the presence of VEGF in primary CNS neuronal cultures.

Activation of receptor-mediated angiogenesis and signaling pathways after VEGF administration in fetal rat CNS explants.

The angiogenic role of vascular endothelial growth factor (VEGF) receptors, flk-1 and flt-1, and their downstream signaling pathways, MAPK/ERK and PI-3 kinase, were examined in a fetal rat cortical explant model after exposure to exogenous VEGF. Treatment with VEGF resulted in substantial neovascularization characterized by increased vascular flk-1 receptor expression, whereas flt-1 receptor protein expression was absent. The specific role of flk-1 receptors in the angiogenic process was confirmed by the addition of antisense oligonucleotides (AS-ODNs) to flk-1, which blocked angiogenesis, whereas AS-ODNs to flt-1 had no effect.

Neurotrophic effects of vascular endothelial growth factor on organotypic cortical explants and primary cortical neurons.

Vascular endothelial growth factor (VEGF) is well known to play an important regulatory role in vascular growth and development. Because gene knock-outs of VEGF and its receptors flk-1 and flt-1 result in early embryonic lethality, determining roles for VEGF in CNS development has been particularly difficult. Recent studies have shown that VEGF is upregulated after various injuries to the adult brain and that the cytokine affords protection to cultured neurons affected by oxidative or excitotoxic stress.

Inhibition of endogenous VEGF impedes revascularization and astroglial proliferation: roles for VEGF in brain repair.

Vascular endothelial growth factor (VEGF) is upregulated following injury to the CNS. Our previous work has shown that exogenous application of VEGF promotes angiogenesis, blood-brain barrier permeability, and astroglial mitogenicity in the traumatized brain. To develop a model that could link endogenously secreted VEGF to brain tissue repair, a specific neutralizing antibody to VEGF was infused by osmotic minipump directly into the neocortex and striatum for up to 1 week.

Changes in astroglial GLT-1 expression after neural transplantation or stab wounds.

Uncontrolled release of glutamate from damaged brain initiates events that result in excitotoxic neuronal death. Glutamate uptake by specialized astroglial transporters is essential for control of extracellular glutamate levels. Many studies have demonstrated a reduction in astrocytic GLT-1 expression after different forms of injury.