RESUMO
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain. 3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine (P7C3-A20) can be neuroprotective in various diseases, including ischemic stroke and neurodegenerative diseases. However, whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear. Therefore, in the present study, we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms. We established a traumatic brain injury rat model using a modified weight drop method. P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury. Severe neurological deficits were found in rats after traumatic brain injury, with deterioration in balance, walking function, and learning memory. Furthermore, hematoxylin and eosin staining showed significant neuronal cell damage, while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis. The presence of autolysosomes was observed using transmission electron microscope. P7C3-A20 treatment reversed these pathological features. Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-II (LC3-II) autophagy protein, apoptosis-related proteins (namely, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 [BNIP3], and Bcl-2 associated x protein [Bax]), and elevated ubiquitin-binding protein p62 (p62) autophagy protein expression. Thus, P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
RESUMO
BACKGROUND AND OBJECTIVES: is commonly used for children undergoing hypospadias repair. However, the safety of caudal block for hypospadias repair in children is controversial in terms of surgical complications such as urethrocutaneous fistula and glans dehiscence. We sought to perform a meta-analysis to estimate the analgesic efficacy and relative complications of caudal block for hypospadias repair in children. METHODS: We identified comparative studies of caudal block versus peripheral nerve block or no caudal block; studies were published or presented through 1 January 2018, and reports of analgesic efficacy or surgical complications of hypospadias repair in children were identified. Peripheral nerve block includes dorsal nerve penile block and pudendal nerve block. Data were abstracted from studies comparing caudal block with peripheral nerve block or no caudal block; original source data were used when available. We prespecified separate assessments of randomized controlled trials (RCTs) and observational studies given the inherent differences between types of study designs. Data from 298 patients in four RCTs and from 1726 patients in seven observational studies were included. RCT and observational data were analyzed separately. RESULTS: In RCTs, caudal blocks (compared with peripheral nerve blocks) showed no detectable differences in terms of need for additional analgesia within 24 hours after the surgery (OR 10.49; 95% CI 0.32 to 343.24; p=0.19), but limited data showed lower pain scores 24 hours after the surgery (standardized mean difference (SMD) 1.57; 95% CI 0.29 to 2.84; p=0.02), a significantly shorter duration of analgesia (SMD -3.33; 95% CI -4.18 to -2.48; p<0.0001) and analgesics consumption. No significant differences were observed in terms of postoperative nausea and vomiting (OR 3.08; 95% CI 0.12 to 77.80; p=0.50) or motor weakness (OR 0.01; 95% CI -0.03 to 0.05; p=0.56). Only one randomized study showed that caudal blocks (compared with peripheral nerve blocks) were associated with detectable differences in urethrocutaneous fistula rate (OR 25.27; 95% CI 1.37 to 465.01; p=0.03) and parental satisfaction rate (OR 0.07; 95% CI 0.02 to 0.21; p<0.00001). In observational studies, caudal block was not associated with surgical complications in all types of primary hypospadias repair (OR 1.83; 95% CI 0.80 to 4.16; p=0.15). To adjust for confounding factors and to eliminate potential selection bias involving caudal block indication, we performed subgroup analysis including only patients with distal hypospadias. This analysis revealed similar complication rates in children who received a caudal block and in children not receiving caudal block (OR 1.02; 95% CI, 0.39 to 2.65; p=0.96). This result further confirmed that caudal block was not a risk factor for surgical complications in hypospadias repair. The direction of outcomes in all the other subgroup analyses did not change, suggesting stability of our results. CONCLUSIONS: In RCTs, only limited data showed peripheral nerve blocks providing better analgesic quality compared with caudal blocks. In real-world non-randomized observational studies with greater number of patients (but with admitted the potential for a presence of selection bias and residual confounders), caudal blocks were not associated with postoperative complications including urethrocutaneous fistula and glans dehiscence.