Activated Microglia Inhibit Axonal Growth through RGMa

By causing damage to neural networks, spinal cord injuries (SCI) often result in severe motor and sensory dysfunction. Functional recovery requires axonal regrowth and regeneration of neural network, processes that are quite limited in the adult central nervous system (CNS). Previous work has shown that SCI lesions contain an accumulation of activated microglia, which can have multiple pathophysiological influences. Here, we show that activated microglia inhibit axonal growth via repulsive guidance molecule a (RGMa). We found that microglia activated by lipopolysaccharide (LPS) inhibited neurite outgrowth and induced growth cone collapse of cortical neurons in vitro—a pattern that was only observed when there was direct contact between microglia and neurons. After microglia were activated by LPS, they increased expression of RGMa; however, treatment with RGMa-neutralizing antibodies or transfection of RGMa siRNA attenuated the inhibitory effects of microglia on axonal outgrowth. Furthermore, minocycline, an inhibitor of microglial activation, attenuated the effects of microglia and RGMa expression. Finally, we examined whether these in vitro patterns could also be observed in vivo. Indeed, in a mouse SCI model, minocycline treatment reduced the accumulation of microglia and decreased RGMa expression after SCI, leading to reduced dieback in injured corticospinal tracts. These results suggest that activated microglia play a major role in inhibiting axon regeneration via RGMa in the injured CNS

Enveloping Sophisticated Tools into Process-Centered Environments

We present a tool integration strategy based on enveloping pre-existing tools without source code modifications or recompilation, and without assuming an extension language, application programming interface, or any other special capabilities on the part of the tool. This Black Box enveloping (or wrapping) idea has existed for a long time, but was previously restricted to relatively simple tools. We describe the design and implementation of, and experimentation with, a new Black Box enveloping facility intended for sophisticated tools --- with particular concern for the emerging class of groupware applications

Ocular-hypertensive response and corneal endothelial changes after intravitreal triamcinolone injections in Chinese subjects: A 6-month follow-up study

Purpose: To assess the intraocular pressure (IOP) and corneal endothelial changes, over a 6-month period, after a single injection of intravitreal triamcinolone (ivTA) in Chinese patients. Methods: A total of 43 eyes of 43 consecutive Chinese patients with various macular diseases received a single bolus injection of 4 mg ivTA, of which, 14 eyes with significant cataracts underwent simultaneous phacoemulsification and primary intraocular lens implantation. IOP was measured preoperatively and weekly in the first month, and then monthly until 6 months postinjection. Specular microscopy was performed on 24 of the 29 eyes without simultaneous cataract surgery, preoperatively and at months 1, 3, and 6. Results: All patients completed 6 months of follow-up. Nine out of 43 (20.9%) eyes had IOP >21 mmHg. Their mean maximum IOP was 29.2 mmHg (range 23.0-37.0), necessitating the use of 2.0 types of topical antiglaucomatous medications on average. The IOP elevation occurred at a mean of 5.2 weeks (range 1-17) postinjection. All IOPs returned to normal, without additional antiglaucomatous medications, by 6 months. There was no statistically significant difference (paired t-test, P < 0.05) in the corneal endothelial cell count and other specular microscopy parameters up to 6 months after the injections. Conclusion: A single 4 mg bolus injection of ivTA appeared to have no harmful effects on the corneal endothelium. IvTA caused transient IOP elevations in 20.9% of Chinese patients, similar to that observed in Caucasians. As the IOP rise can occur as early as 1 week after the injection, early monitoring will help its early detection and prevent optic nerve damage. © 2005 Nature Publishing Group All rights reserved.link_to_subscribed_fulltex