Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, but also at shaping the immune response in order to protect, repair and promote regeneration of spared neural tissue. One of those promising strategies is the intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to promote a phenotype on specific immune cells associated with neuroprotection and repair. In this work, we evaluated if a systemic delivery of IL-4 for a 7-days period was also capable of promoting neuroprotection after SCI by analyzing different neural cells populations and motor recovery. IL-4 treatment promoted an elevation of the anti-inflammatory cytokine IL-10 in the serum both at 24 h and 7 days after injury. Locally, treatment with IL-4 led to a reduction on cells expressing markers associated with inflammation, CD11b/c and iNOS. Importantly, IL-4 treatment increased the neuronal markers βIII-tubulin and NeuN, and the oligodendrocyte marker O4, suggesting a neuroprotective effect. Moreover, 100% of the animals treated with IL-4 were able to recover weight support against only 33% of saline treated animals. Overall, these results show that systemic administration of IL-4 positively impacts different aspects of spinal cord injury, creating a more favorable environment for recovery to take place.
A high‐content screening method to characterize multifunctional multilayer films that combine mechanical adhesion and favorable biological response is reported. Distinct combinations of nanostructured films are produced using layer‐by‐layer methodology and their morphological, physicochemical, and biological properties are analyzed in a single microarray chip. Inspired by the composition of the adhesive proteins in mussels, thin films containing dopamine‐modified hyaluronic acid are studied. Flat biomimetic superhydrophobic patterned chips produced by a bench‐top methodology are used for the build‐up of arrays of multilayer films. The wettability contrasts imprinted onto the chips are allowed to produce individual, position controlled, multilayer films in the wettable regions. The flat configuration of the chip permits to perform a series of nondestructive measurements directly on the individual spots. In situ adhesion properties are directly measured in each spot, showing that nanostructured films richer in dopamine promote the adhesion. In vitro tests show an enhanced cell adhesion for the films with more catechol groups. The advantages presented by this platform include ability to control the uniformity and size of the multilayers films, its suitability to be used as a new low cost toolbox and for high‐content cellular screening, and capability for monitoring in situ a variety of distinct material properties.
Our results suggest that the combined treatment, although simultaneously targeting two excitotoxic-related mechanisms, did not further improve behavioral and histologic outcome when compared with riluzole given alone.
Background
Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord.
Methods
We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury.
Results
We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils’ population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury.
Conclusion
Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.
Citalopram is a selective serotonin reuptake inhibitor, and although widely used as an antidepressant, this drug has also demonstrated interesting repairing properties leading to motor recovery and pathology amelioration in animal models of stroke and degeneration. Here, we tested the efficacy of both 7-day and 8-week citalopram treatment in a contusive spinal cord injury (SCI) rat model. A combination of behavioral tests, histological and serum cytokine analysis was used to assess overall recovery. Despite promoting a mild reduction of inflammatory cells as well as an early, but transient increase of specific serum cytokines, citalopram administration showed no overall beneficial effects on motor performance or lesion extension. Our results do not support citalopram treatment as a therapeutic strategy for SCI.
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