Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria.

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intraperitoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016.

Updated concepts on the pathophysiology and the clinical management of trauma hemorrhage and coagulopathy.

Uncontrolled hemorrhage and subsequent trauma-induced coagulopathy (TIC) are still the principle causes for preventable death after trauma and early detection and aggressive management have been associated with reduced mortality. Despite increasing knowledge about trauma resuscitation, best practice to treat this newly defined entity is still under debate. A synopsis of best current knowledge with reference to the updated European trauma guideline on the management of severe trauma hemorrhage and TIC is presented. The implementation of evidence-based local protocols and algorithms including clinical quality and safety management systems together with parameters to assess key measures of bleeding control and outcome is advocated.

SIRT1 plays a neuroprotective role in traumatic brain injury in rats via inhibiting the p38 MAPK pathway.

Traumatic brain injury (TBI) is a major cause of disability and death in patients who experience a traumatic injury. Mitochondrial dysfunction is one of the main factors contributing to secondary injury in TBI-associated brain damage. Evidence of compromised mitochondrial function after TBI has been, but the molecular mechanisms underlying the pathogenesis of TBI are not well understood. Silent information regulator family protein 1 (SIRT1), a member of the NAD+-dependent protein deacetylases, has been shown to exhibit neuroprotective activities in animal models of various pathologies, including ischemic brain injury, subarachnoid hemorrhage and several neurodegenerative diseases. In this study, we investigated whether SIRT1 also exert neuroprotective effect post-TBI, and further explored the possible regulatory mechanisms involved in TBI pathogenesis. A lateral fluid-percussion (LFP) brain injury model was established in rats to mimic the insults of TBI. The expression levels of SIRT1, p-p38, cleaved caspase-9 and cleaved caspase-3 were all markedly increased and reached a maximum at 12 h post-TBI. In addition, mitochondrial function was impaired, evidenced by the presence of swollen and irregularly shaped mitochondria with disrupted and poorly defined cristae, a relative increase of the percentage of neurons with low ΔΨm, the opening of mPTP, and a decrease in neuronal ATP content, especially at 12 h post-TBI. Pretreatment with the SIRT1 inhibitor sirtinol (10 mg/kg, ip) induced p-p38 activation, exacerbated mitochondrial damage, and promoted the activation of the mitochondrial apoptosis pathway. In contrast, pretreatment with the p38 inhibitor SB203580 (200 µg/kg, ip) significantly attenuated post-TBI-induced expression of both cleaved caspase-9 and cleaved caspase-3 and mitochondrial damage, whereas it had no effects on SIRT1 expression. Together, these results reveal that the 12 h after TBI may be a crucial time at which secondary damage occurs; the activation of SIRT1 expression and inhibition of the p38 MAPK pathway may play a neuroprotective role in preventing secondary damage post-TBI. For this reason, both SIRT1 and p38 are likely to be important targets to prevent secondary damage post-TBI.

[Relationship between early coagulability parameters at admission and outcome in patients with severe heatstroke].

OBJECTIVE: To discuss the relationship between early coagulability parameters at admission in patients with severe heatstroke and their outcome. METHODS: The data from 176 patients with severe heatstroke admitted to Guangzhou General Hospital of Guangzhou Military Command from January 1st, 2002 to August 31st, 2013 were retrospectively analyzed. The patients were divided into survival group (n=150) and non-survival group (n=26) according to the outcome. The incipient values of coagulability function indexes within 24 hours after admission were collected, and prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count (PLT) were compared between two groups to assess the statistically significant indexes for the analysis of the relationship between coagulability parameters and outcome with receiver operator characteristic curve (ROC curve). RESULTS: Compared with those in survival group, PT and APTT were significantly prolonged in non-survival group [PT: 34.0 (18.8, 45.6) s vs. 18.4 (13.8, 18.0) s, Z=-6.09, P=0.000; APTT: 79.7 (41.0, 91.2) s vs. 60.8 (33.4, 41.0) s, Z=-5.08, P=0.000]. The PLT counts were significantly lower in the non-survival group than those in survival group [ 60.8(4.7, 95.3) × 109/L vs. 128.4(79.8, 180.8) × 109/L, Z=-4.34, P=0.000]. ROC curve analysis showed that the area under ROC curve (AUC) for PT in predicting the death of patients with severe heatstroke was 0.874, with standard error of 0.028 and 95% confidence interval (95%CI) of 0.819-0.927 (P=0.000). The best cut-off was 18.5 s, with sensitivity of 76.9% and specificity of 20.0%. AUC for APTT in predicting the death of patients with severe heatstroke was 0.812, with standard error of 0.047 and 95%CI of 0.740-0.903 (P=0.000). The best cut-off was 46.55 s, with sensitivity of 69.2% and specificity of 14.0%. AUC for PLT in predicting the death of patients with severe heatstroke was 0.767, with standard error of 0.040 and 95%CI of 0.688-0.845 (P=0.000). The best cut-off was 86.5 × 109/L, with sensitivity of 68.0% and specificity of 36.8%. CONCLUSIONS: Early prolonged PT and APTT and reduced PLT count are associated with increased risk of death, and it can predict a poor outcome in patients with severe heatstroke.

[Risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders].

OBJECTIVE: to evaluate the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders. METHODS: total 104 cases were collected from January 2005 to June 2009. Twelve variables among patients with PPCs and without PPCs were analyzed by logistic regression analysis. RESULTS: the incidence of postoperative pulmonary complications following transoral operation for the atlanta-axis disorders was 22.1% (23/104). There was significantly difference in 9 variables between patients with PPCs and without PPCs, and 5 variables as serum albumin < 35 g/L (OR = 15.185, P = 0.003), tracheotomy (OR = 32.254, P = 0.015), Frankle grade (OR = 8.866, P = 0.001), the duration of intubation > 4 d (OR = 7.934, P = 0.002), the duration of surgery > 6 h (OR = 16.889, P = 0.006) were found to be significantly related to the development to postoperative pulmonary complications by multivariate analysis. CONCLUSION: serum albumin < 35 g/L, tracheotomy, Frankle grade, the duration of intubation > 4 d, the duration of surgery > 6 h are the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders.