RESUMO
Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.
RESUMO
Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.
RESUMO
To evaluate the accuracy of transcranial color‐code sonography ( TCCS) in non‐invasive assessment of intracranial pressure( ICP ) . TCCS was used to monitor the cerebral hemodynamic parameters of patients with acute severe traumatic brain injury after decompressive craniectomy and make estimation of the non‐invasive intracranial pressure ( ICPtccs) . Methods A total of 91 patients with acute severe traumatic brain injury involved in this retrospective study were divided into the ICP normal group( ≤22 mm Hg ) and the ICP increased group ( ＞22 mm Hg ) . T he correlation and consistency of middle cerebral artery blood flow parameters and ICPtccs with invasive intracranial pressure ( iICP ) were analyzed . According to Glasgow score ( GCS) ,Patients( GCS 3－8) were divided into acute extremely severe traumatic brain injury( GCS 3 －5) and acute severe traumatic brain injury ( GCS 6 －8 ) . A comparison was made of ROC ( ICPtccs) curve and the area under the curve( AUC) between the two groups were cornpared . Results①No statistical differences were found in cerebral hemodynamic parameters between the side with and without decompressive craniectomy in patients with acute severe traumatic brain injury ( all P ＞0 .05 ) . ②M onitored resistive index ( RI) ,pulsatility index ( PI) and ICPtccs between the normal ICP group and the increased ICP group showed statistically significant differences ( all P ＜ 0 .05 ) ,w hile monitored systolic velocity ,diastolic velocity and mean velocity presented no statistically significant difference ( all P ＞0 .05) . T he correlations between RI ,PI with iICP were low ( r＝ 0 .247 ,0 .221 ; all P ＜ 0 .05 ) ,w hile there was a moderate correlation between ICPtccs and iICP( r ＝0 .417 , P ＜0 .001 ) . ③Bland‐Altman plot showed an overestimation of 2 .3 mm Hg ( 95% CI 0 .00－4 .59 mm Hg ) for ICPtccs compared to iICP . ④T he AUC of Glasgow score ( GCS 3－5 and GCS 6－8) in the two groups were 0 .759 ,0 .781 ( all P ＜0 .05) . All the cut‐off points of ICPtccs were 19 mm Hg ,with a sensitivity of 83 .33% ,81 .82% and a specificity of 64 .86% , 75 .68% ,respectively . Pairwise comparison of two AUCs showed no statistical difference ( P ＝ 0 .476) . ICPtccs presented the same ability to estimate ICP in patients with acute severe and extremely severe traumatic brain injury . TCCS could accurately assess the elevation of ICP in 72 .52% patients with acute severe traumatic brain injury . Conclusions TCCS can be used as a non‐invasive screening tool to assess w hether ICP of patients with acute severe traumatic brain injury is elevated and to semi‐quantitatively estimate ICP ,showing useful clinical value .