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A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1b and IL-6 but upregulated TNF-a. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.

Summary To investigate the effects of different carbohydrate (CHO) levels in the diet of Wuchang bream Megalobrama amblycephala, the fish were randomly divided into six treatment groups. Five groups were fed 19, 25, 31, 38 and 47% CHO, respectively, for 8 weeks, and a control group was fed a diet with no CHO. Growth performance and feed utilization were significantly (P < 0.05) affected by the dietary carbohydrate level. Maximum weight gain and specific growth rate occurred at the 31% dietary carbohydrate level. Compared to the control, the 31% CHO group had a significantly increased serum total protein content, respiratory burst activity of leucocytes, serum complement 3 (C3) levels, serum lysozyme activity, serum alkaline phosphatase (AKP) activity and hepatic total antioxidative capacity (T‐AOC), as well as a decrease in serum glutamic‐oxaloacetic transaminase (GOT) activity. Compared to the control, the 47% CHO group had significantly increased serum GOT activity, and a tendency toward an increase in serum cortisol content and a decrease in serum lysozyme activity, hepatic superoxide dismutase (SOD) activity and T‐AOC. The relative level of hepatic heat shock protein 70 (HSP70) mRNA in fish fed the 38% CHO diet was significantly higher than those of fish fed the 19, 25 and 31% CHO diets, respectively (P < 0.05). After challenge with Aeromonas hydrophila, fish fed the 47% CHO had the significantly lowest post‐challenge survival, and fish fed the 31% CHO had the significantly highest post‐challenge survival (P < 0.05). The results of this study suggest that ingestion of excessive dietary CHO can impact the non‐specific immune responses, decrease the hepatic antioxidant abilities, and thus affect the health status of M. amblycephala.

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Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1 hour. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and improved immunogenicity.

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