K.J. Duberstein

Gait analysis in a pre- and post-ischemic stroke biomedical pig model

Severity of neural injury including stroke in human patients, as well as recovery from injury, can be assessed through changes in gait patterns of affected individuals. Similar quantification of motor function deficits has been measured in rodent animal models of such injuries. However, due to differences in fundamental structure of human and rodent brains, there is a need to develop a large animal model to facilitate treatment development for neurological conditions. Porcine brain structure is similar to that of humans, and therefore the pig may make a more clinically relevant animal model. The current study was undertaken to determine key gait characteristics in normal biomedical miniature pigs and dynamic changes that occur post-neural injury in a porcine middle cerebral artery (MCA) occlusion ischemic stroke model. Yucatan miniature pigs were trained to walk through a semi-circular track and were recorded with high speed cameras to detect changes in key gait parameters. Analysis of normal pigs showed overall symmetry in hindlimb swing and stance times, forelimb stance time, along with step length, step velocity, and maximum hoof height on both fore and hindlimbs. A subset of pigs were again recorded at 7, 5 and 3 days prior to MCA occlusion and then at 1, 3, 5, 7, 14 and 30 days following surgery. MRI analysis showed that MCA occlusion resulted in significant infarction. Gait analysis indicated that stroke resulted in notable asymmetries in both temporal and spatial variables. Pigs exhibited lower maximum front hoof height on the paretic side, as well as shorter swing time and longer stance time on the paretic hindlimb. These results support that gait analysis of stroke injury is a highly sensitive detection method for changes in gait parameters in pig.

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model.

Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.

Effects of vitamin E supplementation and training on oxidative stress parameters measured in exercising horses

Exercise places an increased demand on the body’s systems, both to provide fuel for working musculature and to neutralize and dispose of toxic build-up. By-products of demanding performance are reactive free radicals. Dietary consumption of vitamin E, an antioxidant, may be a plausible way to reduce free radical damage. The present study examined the effects of supplemental dietary vitamin E on the presence of oxidation products and antioxidant capacity in blood and tissue of exercising horses. Eight Thoroughbred horses were used in a crossover design study, with one group consuming a diet containing vitamin E at the 1989 National Research Council (NRC) level recommended for horses in moderate to intense work (80 IU kg DM [National Research Council (1989). Nutrient Requirements of Horses. 5th revised edn.; Washingto, DC: National Academy Press, pp. 48]), and the second group being fed the control diet plus 3000 IU day DL-a-tocopheryl acetate. The horses underwent an adaptation phase, an 8-week training programme and a final standard exercise test (SET) during which the horses ran on a 68 incline to exhaustion, and then a washout phase. Horses were then crossed over to opposite treatment groups and these phases repeated. Blood samples were collected at specific points before and after exercise during the training period and before and after performing the SET. Neither plasma vitamin E nor thiobarbituric acid-reactive substance concentrations were influenced by supplemental vitamin E. Blood Troloxequivalent antioxidant capacity values increased (P , 0.05) following 5 weeks of training in both groups, indicating improved antioxidant capacity as horses became fitter. Vitamin E supplementation did not alter plasma reduced, oxidized or total glutathione levels, nor the percentage of glutathione in the reduced form during the training period. However, vitamin E did cause an elevation in the percentage of glutathione existing in the reduced form following a SET as compared with the control diet (P , 0.006). This is possibly due to lower plasma oxidized glutathione levels in vitamin E-treated horses (P , 0.03). This study indicates that vitamin E supplementation above NRC levels can influence certain measures of oxidative stress in intensely exercising horses, and training has the ability to improve the antioxidant status of the animal.