Rationale: Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation. Methods: Spinal cord inflammation after intravenous OEC transplantation was detected in vivo and ex vivo by translocator protein PET tracer [ 18 F]F-DPA. To track transplanted cells, OECs were transduced with enhanced green fluorescent protein (eGFP) and HSV1-39tk using lentiviral vector and were monitored by fluorescence imaging and [ 18 F]FHBG study. Protein microarray analysis and ELISA studies were employed to analyze differential proteins in the injured spinal cord after OEC transplantation. The anti-inflammation function of the upregulated protein was also proved by in vitro gene knocking down experiments and OECs/microglia co-culture experiment. Results: The inflammation in the spinal cord was decreased after OEC intravenous transplantation. The HSV1-39tk-eGFP-transduced OECs showed no accumulation in major organs and were found at the injury site. After OEC transplantation, in the spinal cord tissues, the interleukin-1 receptor antagonist (IL-1Ra) was highly upregulated while many chemokines, including pro-inflammatory chemokines IL-1α, IL-1β were downregulated. In vitro studies confirmed that lipopolysaccharide (LPS) stimulus triggered OECs to secrete IL-1Ra. OECs significantly suppressed LPS-stimulated microglial activity, whereas IL-1Ra gene knockdown significantly reduced their ability to modulate microglial activity. Conclusion: The OECs that reached the lesion site were activated by the release of pro-inflammatory cytokines from activated microglia in the lesion site and secreted IL-1Ra to reduce neuroinflammation. Intravenous transplantation of OECs has high therapeutic effectiveness for the treatment of SCI via the secretion of IL-1Ra to reduce neuroinflammation.
Early-life exposure to pollutants, such as lead, may have long-lasting consequences on health, behavior, and cognition. However, experiments on delayed effects of specific pollutants are very rare in wild animals. We experimentally exposed wild nestling great tits (Parus major) to dietary lead (high, low, or control group) in levels relevant to exposure levels of wild populations in Europe and studied delayed effects on phenotypic and behavioral traits in captivity. We also included a group of birds from a vicinity of a copper smelter, exposed to a mixture of toxic metals and altered food supply during development. This experimental setup allowed us to compare the strength of direct (exposure to lead per se) and indirect (pollution-related changes in diet) effects of pollutants. Our experimental lead treatment significantly increased lead levels in bone and feces compared with controls. However, we found no carry-over effect of early-life dietary lead on morphology, plumage coloration, or heat shock proteins. Treatment did not affect activity, exploration, neophobia, or success in learning and spatial memory task. We conclude that with the exposure levels and relatively short exposure period used, delayed effects on the measured traits were not found. However, it is important to further study other types of behavioral traits and ultimately fitness effects.
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