(* p?0.001) Open in a separate window Fig. doses of 4??106 hUCB cells with plasma beginning at 7?days ML241 after stereotaxic 6-OHDA lesion, then behaviorally and immunohistochemically evaluated over 56?days post-lesion. Whereas vehicle-treated lesioned animals exhibited the typical 6-OHDA neurobehavioral symptoms, hUCB and plasma-treated lesioned animals showed significant attenuation of motor function, gut motility, and nigral dopaminergic neuronal survival, combined with diminished pro-inflammatory microbiomes not only in the nigra, but also in the gut. Altogether these data support a regenerative medicine approach for PD by sequestering inflammation and neurotoxicity through correction of gut dysbiosis. groupManz et al. 1996 EREC4825-GCTTCTTAGTCAGGTACCG-3Clostridium cluster XIVaFranks et al. 1998 LAB1585-GGTATTAGCA(C/T)CTGTTTCCA-3groupHarmsen et al. 1999  Open in a separate window Statistical Analysis Behavioral results, image data, and microbiome analysis are expressed as mean??S.D. Statview (Abacus Corporation) was used to perform these statistical analyses. The study results were evaluated using one-way ANOVA with Bonferroni post-hoc analysis. A significant value was determined to be Col4a2 p?0.05. Results hUCB+P Attenuates Motor Deficits in the 6-OHDA Model of PD In this study, the efficacy of a combined cord blood cell and cord blood plasma (hUCB+P) therapy was investigated in the 6-OHDA lesion rat model of PD. There were no adverse reactions observed in any of the animals that received iv hUCB+P and none of the animals were withdrawn from the study before completion. Motor function was assessed in PD animals by observing both apomorphine-induced rotational behavior (Fig.?1) and elevated body swing testing (Fig.?2a). This motor testing was used to validate the induction of PD-like pathology resulting from unilateral stereotaxic injection of 6-OHDA, and to assess any potential therapeutic benefit from hUCB+P administration. The induction of rotational behavior and body swing bias observed in vehicle-treated animals indicated the establishment of PD-like neurological and motor symptoms that are consistent with PD progression. Lesioned animals treated with hUCB+P exhibited a significant reduction in total apomorphine-induced contralateral turns at the 28, 42, and 56?day time points compared to vehicle-treated lesioned animals (p?0.05). Additionally, elevated body swing testing revealed a significant reduction in swing bias observed from lesioned animals that received hUCB+P versus the vehicle group. (p?0.001). Motor coordination test using the Rotarod was employed to determine ML241 overall motor coordination in the study animals (Fig. ?(Fig.2b).2b). Lesioned animals that received the hUCB+P after 6-OHDA showed improvement at the 28?day time point over vehicle-treated lesioned animals, although significance was not observed at the other time points assayed. Locomotor performance using the beam walk test (Fig. ?(Fig.2c)2c) was also observed for all animal groups and time points in this study. Lesioned animals that received hUCB+P showed significantly improved beam walk scores when tested at Day 28, Day 42, and Day 56 after 6-OHDA induction (p?0.001). Open in a separate window Fig. 1 Administrations of cord blood cells with plasma in the 6-OHDA PD rat model: Assessment of 6-OHDA induced neurological deficits. Asymmetrical motor behavior was assessed using apomorphine-induced rotational behavior post-treatment on Day 14, 28, 42, and 56. Stem cell administration significantly reduced the total number of apomorphine-induced contralateral turns starting at day 28 and persisted up to day 56 post-lesion. (* p?0.001) Open in a separate window Fig. 2 Administrations of cord ML241 blood cells with plasma in the 6-OHDA PD rat model: Assessment of 6-OHDA induced neurological deficits (a). Neurological function was also assessed using the elevated body swing test at Day 14, 28, 42, and 56 post treatment. Animals receiving stem cells exhibited a significant reduction in swing bias observed on Days 28, 42, and 56. (*** p?0.001). Administrations of cord blood cells with plasma in the 6-OHDA PD rat model: Assessment of motor function improvement (b). Motor coordination and balance were assessed post-treatment on Day 28, 42, and 56. Improvements in motor coordination were observed at 28?days with combined cord blood cell and plasma treatment, but not.