Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel þ BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate (Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel þ BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.
How can you combine professional-quality research with discovery-based undergraduate education? The UCLA Undergraduate Consortium for Functional Genomics provides the answer
Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.
Inversely related HCEnC expression levels of ZEB1 and COL4A3 in PPCD3 indicate that ZEB1-mediated alterations in COL4A3 expression are most likely associated with the pathogenesis of this corneal endothelial dystrophy. However, the demonstration of COL4A3 expression in healthy adult primary HCEnCs suggests that PPCD3 is more likely to involve an alteration in the timing and/or degree of COL4A3 expression than to result from the dichotomous change implied by the previously proposed ectopic expression model.
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