METHODS: We employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation.
RESULTS: Significant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group.
CONCLUSIONS: Suppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.
METHODS: This retrospective study was conducted in the participating centers of the Pan-Asian Trauma Outcome Study from October 2015 to December 2020. Subjects who reported "school" as the site of injury were included. Major trauma was defined as an Injury Severity Score (ISS) value of ≥16.
RESULTS: In total, 1305 injury cases (1.0% of 127,715 events) occurred at schools. Among these, 68.2% were children. Unintentional injuries were the leading cause and intentional injuries comprised 7.5% of the cohort. Major trauma accounted for 7.1% of those with documented ISS values. Multivariable regression revealed associations between major trauma and factors, including age, intention of injury (self-harm), type of injury (traffic injuries, falls), and body part injured (head, thorax, and abdomen). Twenty-two (1.7%) died, with six deaths related to self-harm. Females represented 28.4% of injuries but accounted for 40.9% of all deaths.
CONCLUSIONS: In Asia, injuries at schools affect a significant number of children. Although the incidence of injuries was higher in males, self-inflicted injuries and mortality cases were relatively higher in females.
IMPACT: Epidemiological data and risk factors for major trauma resulting from school injuries in Asia are lacking. This study identified significant risk factors for major trauma occurring at schools, including age, intention of injury (self-harm), injury type (traffic injuries, falls), and body part injured (head, thoracic, and abdominal injuries). Although the incidence of injuries was higher in males, the incidence of self-harm injuries and mortality rates were higher in females. The results of this would make a significant contribution to the development of prevention strategies and relative policies concerning school injuries.