Oxygen-induced retinopathy in the mouse.

PURPOSE: To develop oxygen-induced retinopathy in the mouse with reproducible and quantifiable proliferative retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for retinal neovascularization in retinopathy of prematurity (ROP) and other vasculopathologies. METHODS: One-week-old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A novel fluorescein-dextran perfusion method has been developed to assess the vascular pattern. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in 6 microns sagittal cross-sections. Cross-sections were also stained for glial fibrillary acidic protein (GFAP). RESULTS: Fluorescein-dextran angiography delineated the entire vascular pattern, including neovascular tufts in flat-mounted retinas. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery. Retinal neovascularization occurred in all the pups between postnatal day 17 and postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of 9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes in the normoxia control (P < 0.0001). Proliferative vessels were not associated with GFAP-positive astrocyte processes. CONCLUSIONS: The authors have described a reproducible and quantifiable mouse model of oxygen-induced retinal neovascularization that should prove useful for the study of pathogenesis of retinal neovascularization as well as for the study of medical intervention for ROP and other retinal angiopathies

The Impact of Different Types of Assistive Devices on Gait Measures and Safety in Huntington's Disease

BACKGROUND: Gait and balance impairments lead to frequent falls and injuries in individuals with Huntington's disease (HD). Assistive devices (ADs) such as canes and walkers are often prescribed to prevent falls, but their efficacy is unknown. We systematically examined the effects of different types of ADs on quantitative gait measures during walking in a straight path and around obstacles. METHODS: Spatial and temporal gait parameters were measured in 21 subjects with HD as they walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6 commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3 or 4 wheeled walker). Subjects also were timed and observed for number of stumbles and falls while walking around two obstacles in a figure-of-eight pattern. RESULTS: Gait measure variability (i.e., coefficient of variation), an indicator of fall risk, was consistently better when using the 4WW compared to other ADs. Subjects also walked the fastest and had the fewest number of stumbles and falls when using the 4WW in the figure-of-eight course. Subjects walked significantly slower using ADs compared to no AD both across the GAITRite and in the figure-of-eight. Measures reflecting gait stability and safety improved with the 4WW but were made worse by some other ADs

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression

Optic nerve injury alters basic fibroblast growth factor localization in the retina and optic tract

Basic fibroblast growth factor (bFGF) is thought to be a trophic factor for several classes of neurons. Its distribution changes in response to cortical neural injury. We have determined the effect of injury to the optic nerve on localization of bFGF in the rodent retina and visual pathways. Our observations were confirmed by using different antisera and monoclonal antibodies. While photoreceptors normally contain virtually no bFGF, crushing the optic nerve causes a striking increase, over a period of several weeks, in the amount of bFGF in retinal photoreceptors. Since photoreceptors do not synapse directly upon the injured ganglion cells, intermediary cells must participate in the cascade of events that results in the elevated bFGF. In light of the observation that exogenous bFGF protects photoreceptors from photodamage (Faktorovich et al., 1992), this increase in bFGF in photoreceptors may explain, in part, why crushing the optic nerve protects photorecptors against photodamage (Bush and Williams, 1991). Whereas bFGF is constitutively found in glia in the optic nerve, little bFGF is found in glia in the optic tract. However, damage to the optic nerve increases bFGF in astrocytes in the optic tract. This change occurs within days, suggesting that a relatively direct signal may intervene between the injured axon and the adjacent glial cells. Thus, despite the fact that the optic nerve and optic tract are contiguous structures through which axons of retinal ganglion cells project, the glial elements in these structures express distinct properties, because of differences in either glial subclasses or microenvironment

Dopaminergic Modulation of Semantic Priming in Parkinson Disease

Looking out over Frenchman Bay and the Porcupine Islands northeast of town from Acadia National Park; Bar Harbor is a town on the northeast shore of Mount Desert Island in Hancock County, Maine. As of the 2010 census, its population is 5,235. Bar Harbor is a famous summer colony in the Down East region of Maine. In 1604 French explorer Samuel de Champlain ran aground on the island, which he named Isles des Monts Deserts, meaning "island of barren mountains". It was first settled by the British in 1763, and originally named Eden (after Sir Richard Eden). By 1880, there were 30 hotels, with tourists arriving by train and ferry to the Gilded Age resort that would rival Newport. On March 3, 1918, Eden was renamed Bar Harbor. In 1947, a month long wildfire destroyed the east side of the island, including 67 of the palatial homes. The business district was spared. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 7/22/2012

The Step Test Evaluation of Performance on Stairs (STEPS): Validation and reliability in a neurological disorder.

BackgroundIndividuals with neurological disorders often have difficulty negotiating stairs that can lead to injurious falls. Clinicians lack a clinical tool to identify impairments in stair negotiation and to assist their decision making regarding treatment plans to improve stair performance and safety. We developed a new tool called the Step Test Evaluation of Performance on Stairs (STEPS) that is designed to assess stair performance and safety in neurological populations.ObjectivesThis study aimed to determine interrater and intrarater reliability of STEPS and its concurrent content validity to various clinical balance and mobility measures using individuals with Huntington's disease (HD) as the first test population.MethodsForty individuals with HD (mean age 50.35) participated. Three observers rated live performances of the STEPS (interrater reliability) and seven observers rated videotaped performances twice (intrarater reliability). STEPS scores correlated with clinical mobility and balance test scores.ResultsExcellent inter- and intrarater reliability (ICCs = 0.91 and 0.89 respectively) and good internal consistency (α = 0.83) were found. Better STEPS performance correlated with better performance on co-administered motor and mobility measures and Stair Self-Efficacy scores. Per multivariable regression analysis, the Unified Huntington's Disease Rating Scale modified motor score and descent time were significant predictors of STEPS performance.ConclusionsThe STEPS tool is easy to administer, requires no special devices and can be completed in less than five minutes. In the HD test population, it shows high reliability and validity making it a potentially useful tool for assessing maneuverability and safety on stairs in HD. The results suggest that the STEPS tool warrants further study to determine STEPS cut-off values for fall prediction in HD and may prove useful as an assessment tool for other neurological disorders

Coefficient of Variation of Gait measures across all walking conditions: mean, (standard deviation).

<p>Abbreviations: no AD, no assistive device; StW, standard walker; 2WW, two wheeled walker; 3WW, three wheeled walker; 4WW, four wheeled walker; CV, Coefficient of Variation;</p><p>*significantly different than no AD at p<.05;</p>†<p>significantly different than cane at p<.05;</p>#<p>significantly different than StW at p<.05;</p>∞<p>significantly different than 3WW at p<.05;</p><p>significantly different from 4WW at p<.05;</p><p>significantly different from 2WW and 3WW at p<.05;</p>‡<p>significantly different from 2WW, 3WW, 4WW at p<.05;</p>§<p>significantly different than 2WW, 4WW at p<.05;</p>Ψ<p>significantly different than cane and 4WW at p<.05.</p

Coefficients of Variation.

<p>Comparison of mean coefficients of variation across six walking conditions: (A) step time and (B) stride length coefficients of variation (CV) with standard deviation. Variability was consistently low when using the four-wheeled walker (4WW); no AD, no assistive device; StW, standard walker; 2WW, two-wheeled walker; 3WW, three-wheeled walker; *significantly different than no AD at <i>p</i><.05. * significantly different than no AD at p<.05; † significantly different than cane at p<.05; # significantly different than StW at p<.05; ∞ significantly different than 3WW at p<.05; § significantly different than 2WW, 4WW at p<.05; Ψ significantly different than cane and 4WW at p<.05.</p

Gait measures across all walking conditions: mean, (standard deviation).

<p>Abbreviations: no AD, no assistive device; StW, standard walker; 2WW, two wheeled walker; 3WW, three wheeled walker; 4WW, four wheeled walker; CV, Coefficient of Variation;</p><p>*significantly different than no AD at p<.05;</p><p>**significantly different than all other conditions at p<.05;</p>†<p>significantly different than cane at p<.05;</p>#<p>significantly different than StW at p<.05;</p>∞<p>significantly different than 3WW at p<.05;</p>‡<p>significantly different from 2WW, 3WW, 4WW at p<.05;</p>§<p>significantly different than 2WW, 4WW at p<.05.</p