ABSTRACT
Background: In skull base surgery, zygomaticectomy is an effective method to increase surgical exposure and reduce brain retraction. However, the traditional zygomaticectomy methods are complicated and more invasive. Objective: To improve the procedure of zygomaticectomy, we introduced a modified technique to harvest integrated zygomatic arch-temporal bone flap. Subjects and Methods: A modified technique to section the zygomatic arch integrated with the temporal bone flap was described in the present work. This technique was applied in eight skull base lesion patients. The improved surgical angle was measured using Osirix software. Results: The surgical exposure is satisfied and no temporal lobe contusion or severe complications occurred in the patients. An increased surgical angle was obtained by zygomatic arch removing, with a mean value of 13.31°. Conclusions: This integrated zygomatic arch-temporal bone flap technique achieved increased exposure, decreased temporal lobe retraction, and minimal bone loss, leading to better cosmetics and functional reconstructions.
Subject(s)
Craniotomy , Temporal Bone , Zygoma , Craniotomy/methods , Humans , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/methods , Plastic Surgery Procedures , Skull Base/surgery , Surgical Flaps , Temporal Bone/surgery , Zygoma/surgeryABSTRACT
Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.
ABSTRACT
Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.
