Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

The relationship of single unit activity to limb movements guided by visuospatial cues supports the view that the premotor cortex is a distinct cortical field within the somatic sensorimotor cortex. The premotor cortex is similar to the precentral motor cortex (MI) in that most of its units are clearly related to voluntary movements but differs from MI by its higher threshold for microstimulation-evoked movements, its cytoarchitecture, and the presence of a larger population of neurons with activity related to the occurrence of visuospatial signals rather than, or in addition to, the movement cued by those signals.

Evidence is accumulating that lipids play important roles in permeabilization of the mitochondria outer membrane (MOM) at the early stage of apoptosis. Lamellar phosphatidylcholine (PC) and nonlamellar phosphatidylethanolamine (PE) lipids are the major membrane components of the MOM. Cardiolipin (CL), the characteristic lipid from the mitochondrial inner membrane, is another nonlamellar lipid recently shown to play a role in MOM permeabilization. We investigate the effect of these three key lipids on the gating properties of the voltage-dependent anion channel (VDAC), the major channel in MOM. We find that PE induces voltage asymmetry in VDAC currentvoltage characteristics by promoting channel closure at cis negative applied potentials. Significant asymmetry is also induced by CL. The observed differences in VDAC behavior in PC and PE membranes cannot be explained by differences in the insertion orientation of VDAC in these membranes. Rather, it is clear that the two nonlamellar lipids affect VDAC gating. Using gramicidin A channels as a tool to probe bilayer mechanics, we show that VDAC channels are much more sensitive to the presence of CL than could be expected from the experiments with gramicidin channels. We suggest that this is due to the preferential insertion of VDAC into CL-rich domains. We propose that the specific lipid composition of the mitochondria outer membrane and/or of contact sites might influence MOM permeability by regulating VDAC gating.

Objective-To determine whether Adaptive Physical Activity (APA-stroke), a community-based exercise program for participants with hemiparetic stroke, improves function in the community.Methods-Nonrandomized controlled study in Tuscany, Italy, of participants with mild to moderate hemiparesis at least 9 months after stroke. Forty-nine participants in a geographic health authority (Empoli) were offered APA-stroke (40 completed the study). Forty-four control participants in neighboring health authorities (Florence and Pisa) received usual care (38 completed the study). The APA intervention was a community-based progressive group exercise regimen that included walking, strength, and balance training for 1 hour, thrice a week, in local gyms, supervised by gym instructors. No serious adverse clinical events occurred during the exercise intervention. Outcome measures included the following: 6-month change in gait velocity (6-Minute Timed Walk), Short Physical Performance Battery (SPPB), Berg Balance Scale, Stroke Impact Scale (SIS), Barthel Index, Hamilton Rating Scale for Depression, and Index of Caregivers Strain.Results-After 6 months, the intervention group improved whereas controls declined in gait velocity, balance, SPPB, and SIS social participation domains. These between-group comparisons were statistically significant at P < .00015. Individuals with depressive symptoms at baseline improved whereas controls were unchanged (P < .003). Oral glucose tolerance tests were performed on a subset of participants in the intervention group. For these individuals, insulin secretion declined 29% after 6 months (P = .01).Address correspondence to Mary Stuart, ScD, Health Administration and Policy Program, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250. stuart@umbc.edu. Drs Stuart and Benvenuti contributed to this work equally.For reprints and permission queries, please visit SAGE's Web site at http://www.sagepub.com/journalsPermissions.nav. NIH Public Access Author ManuscriptNeurorehabil Neural Repair. Author manuscript; available in PMC 2011 January 20. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptConclusion-APA-stroke appears to be safe, feasible, and efficacious in a community setting. KeywordsStroke; Exercise; Community; Rehabilitation Stroke is one of the leading causes of death and long-term disability. 1 The Framingham study found that at 6 months following a stroke (ie, after the period of natural recovery 2 ) 50% of stroke survivors aged 65 years or older had some hemiparesis and 30% were unable to walk without assistance. 3 Due in part to the sedentary lifestyle associated with these limitations, the stroke survivor is at increased risk of diabetes, glucose intolerance, heart disease, subsequent stroke death, and depression. 4,5 There is substantial evidence supporting a protective role for exercise in the prevention of stroke. 1 For stroke survivors, increasing evidence also links exercise to improved cardiovascular health, with decreased ris...