Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The neurovascular unit maintains blood-brain barrier and vascular integrity through interactions among glial cells, pericytes and endothelial cells. Trauma-induced neuroinflammation and oxidative stress may act as initiating factors for pathological damage after TBI, which in turn impairs cerebral microcirculatory function. Studies have shown that the tumor necrosis factor α (TNF-α)/nuclear factor-κB (NF-κB) pathway regulates inflammation and oxidative damage, but its role in pericyte-mediated cerebral microcirculation are currently unknown. Herein, we assessed TNF-α/NF-κB signaling and inducible nitric oxide synthase (iNOS), and the effects of the TNF-α inhibitor infliximab after TBI. Whether pericyte damage is dependent on the TNF-α/NF-κB/iNOS axis was also evaluated to explore the mechanisms underlying disturbances in the microcirculation after TBI. Microglia are activated after TBI to promote inflammatory factors and free radical release, and upregulate NF-κB and iNOS expression. After lipopolysaccharide treatment, the activity of TNF-α/NF-κB/iNOS in BV2 cells was also upregulated. Inhibition of TNF-α using infliximab reduced NF-κB phosphorylation and nuclear translocation and downregulated iNOS expression, which attenuated the inflammation and oxidative damage. Meanwhile, inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and microcirculation perfusion after TBI. In conclusion, our study suggests that microglia released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation.
每年全球有数百万人发生颅脑损伤(TBI),给社会经济造成了巨大的负担。重型颅脑损伤(sTBI)可能导致昏迷、脑水肿、颅内压升高、脑疝等严重后果,引起多种并发症,甚至导致死亡。由于TBI的复杂性和多样性,临床医生在诊断和治疗过程中需要综合考虑伤情的不同方面。本文探讨了不同类型sTBI的临床表现、影像学诊断和各种治疗方法,尤其强调复杂病例的诊断和微创技术的应用,有助于改善患者的救治质量,为临床实践提供有益的指导。
Objective:To investigate the effect of infliximab (IFX) on neurological function in mice after traumatic brain injury (TBI) and the role of nuclear factor-κB (NF-κB)/inducible nitric oxide lyase (iNOS) signaling in it.Methods:Seventy-two healthy adult male C57BL/6 mice were randomly divided into sham-operated group, TBI group, and TBI+IFX group ( n=24). The mouse TBI models were established by controlled cortical impact method. IFX (dissolved in normal saline at a concentration of 2.5 mg/mL and a dose of 10 μg/g) was administered intraperitoneally into the mice of TBI+IFX group 30 min after modeling once daily for 3 d; mice in the sham-operated group and TBI group were given the same amount of saline intraperitoneally at the same time points for 3 d. Neurological deficits (Garcia scores) were assessed one, 3 and 7 d after modeling; blood-brain barrier permeability was detected by Evans blue staining, and brain tissue water content was measured by dry and wet weight method; Nissl staining was used to detect the percentage of injured neurons in brain tissues; the percentage of apoptotic neurons was detected by Tunel staining; immunofluorescent double-labeling was used to detect the expressions of caspase-3 and neuronal nuclear antigen (NeuN) in neurons; immunohistochemical staining was used to detect the microglia marker ionized calcium binding adaptor molecule-1 (IBa-1) expression; ELISA was used to detect the expressions of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, interferon [IFN]-γ) and free radicals (oxygen free radicals [ROS], nitrogen free radicals [RNS]) in the brain tissues; and immunofluorescent staining and Western blotting were used to detect the expressions of nuclear factor (NF)-κB/inducible nitric oxide synthase (iNOS). Results:(1) One, 3 and 7 d after modeling, the Garcia scores showed significant differences among the three groups ( P<0.05); as compared with the TBI group, the TBI+IFX group had significantly increased Garcia scores 3 and 7 d after modeling ( P<0.05). (2) Three d after modeling, as compared with those in the TBI group, Evans blue leakage ([18.45±1.32] μg/g vs. [16.38±1.25] μg/g), brain water content ([81.56±0.96]% vs. [79.97±0.79]%), percentage of injured neurons ([79.50±5.85]% vs. [68.81±7.47]%), and percentage of apoptotic neurons ([41.93±7.49]% vs. [30.59±8.60]%) in mice of the TBI+IFX group were significantly deceased ( P<0.05). Three d after modeling, immunofluorescent double labeling showed that the relative caspase-3 expression in the TBI+IFX group (0.76±0.16) was significantly decreased as compared with the TBI group (1.11±0.23, P<0.05). Immunohistochemical staining and ELISA results showed that as compared with those in the TBI group, the Iba-1 staining scores, TNF-α, IL-1β, IL6 and IFN-γ levels, and ROS and RNS contents in TBI+IFX group were significantly decreased ( P<0.05). Immunofluorescent staining and Western blotting showed that as compared with the TBI group, the TBI+IFX group had significantly decreased expressions of NF-κB p65, iNOS and phosphorylated nuclear factor-κB inhibitor-α, and statistically inhibited nuclear translocation of NF-κB ( P<0.05). Conclusion:IFX can reduce inflammatory response and oxidative stress response, and play a neuroprotective role, which is related to its inhibition of downstream NF-κB/iNOS pathway activation.
•PCNSL originating from the intracranial venous system is very rare.•The radiological features of PCNSL may be nonspecific.•Neurosurgeons can mistake it for meningiomas.•Complete resection of PCNSL is usually not possible.
Objective:To explore the preoperative predictors of concurrent encephalocele during decompressive craniectomy in patients with traumatic brain hernia.Methods:One hundred and three patients with the diagnosis of severe traumatic brain hernia treated in Neurosurgery Department of the 900th Hospital of the Joint Logistics Team from January 2017 to December 2020 were retrospectively analyzed. According to whether acute encephalocele occurred during operation, they were divided into acute encephalocele group and non-encephalocele group. The prognosis of the 2 groups at 3 months after operation was compared, The risk factors of intraoperative acute encephalocele were analyzed by univariate and multivariate Logistic regression, and then the preoperative predictors of encephalocele were explored.Results:Of the 103 patients in this group, 24 had acute encephalele (23.3%). The poor prognosis rate within 3 months in the acute encephalocele group (70.83%) was significantly higher than that in the non-encephalocele group (40.51%) (P<0.05). Univariate analysis showed that there were significant differences in age classification, preoperative pupil changes, preoperative history of hypoxia or hypoxemia, preoperative Helsinki CT score and preoperative diffuse brain swelling between encephalocele group and non-encephalocele group (P<0.05). Binary Logistic regression analysis showed that the risk of acute encephalocele was significantly increased in age <60 years old, preoperative mydriasis, and Helsinki CT score≥8.Conclusion:The preoperative high risk predictors of acute encephalocele were age <60 years old preoperative dilated pupil, and Helsinki CT score ≥8. The evaluation of above factors has positive clinical reference for the prevention of acute encephalocele before the operation.
Objective:To investigate the clinical value of ventricular intracranial pressure monitoring (V-ICPM) in gradient decompression for patients with traumatic cerebral hernia.Methods:The clinical data of 103 patients with traumatic cerebral hernia admitted to our hospital from October 2016 to October 2020 were retrospectively analyzed. These patients were divided into observation group ( n=49) and control group ( n=54) according to whether V-ICPM was applied. Patients in the observation group accepted V-ICPM before gradient decompression, and patients in the control group accepted gradient decompression directly. Incidence of malignant encephalocele, clinical short-term and long-term efficacies, and complications were compared between the two groups. According to intracranial pressure (ICP), the patients were divided into normal or slightly increased ICP (≤22 mmHg), moderate increased ICP (23-40 mmHg) and severe increased ICP (>40 mmHg); the relationship between ICP and prognoses was analyzed in the observation group. Results:(1) The incidences of intraoperative malignant encephalocele in the observation group (16.33%) were slightly lower than that in the control group (29.63%), without significant difference ( P>0.05). Twenty four h after gradient decompression, pupils recovered in 35 patients (71.43%) from the observation group and 28 patients (51.85%) from the control group, significant difference in the pupils recovery rate was noted between the two groups ( χ2=4.145, P=0.042); the Glasgow Coma Scale (GCS) scores between the observation group (8.43±2.56) and control group (7.39±2.47) showed statistical differences ( t=-2.095, P=0.039). Three months after gradient decompression, there were 7 patients with Glasgow Outcome Scale (GOS) scores of 5, 18 patients with scores of 4, 10 patients with scores of 3, 8 patients with scores of 2, and 6 patients with score of 1 in the observation group; there were 12 patients with GOS scores of 5, 17 patients with scores of 4, 12 patients with scores of 3, 7 patients with scores of 2, and 6 patients with score of 1 in the control group; the difference was not statistically significant ( Z=-0.681, P=0.496). (2) The higher the ICP in the observation group (initially and when the dura mater is cut), the worse the prognosis. Conclusion:The application of V-ICPM before gradient decompression cannot further improve the long-term prognosis of the patients, but it can provide intraoperative reference and prognosis prediction for the operators.
Objective:To explore the early clinical treatment strategy of open traumatic brain injury (TBI).Methods:The clinical data of 50 patients with open TBI treated in Neurosurgery Department of the 900th Hospital of Joint Logistics Team from June 2010 to January 2020 were selected. According to the operation time, they were divided into the early group (<6 h, 25 cases) and the late group (6-12 h, 25 cases). Twelve patients with skull base fracture phaseⅠ were treated with skull base reconstruction. After 72 h, the GOS score, clinical deterioration outcome and postoperative complications were compared between the two groups.Results:All 12 patients with skull base fracture underwent skull base reconstruction in phase Ⅰ, and there were no complications such as meningoencephalocele and cerebrospinal fluid leakage. The postoperative 72 h GOS score in the early group was higher than in the late group. The incidence of postoperative 72 h death, severe TBI, intracranial infection, stress ulcer, epilepsy and pulmonary infection in the early group was lower than in the late group (P<0.05).Conclusion:For open TBI, eraly operation and skull base reconstruction in phase Ⅰ can effectively reduce the postoperative complications and improve the prognosis of patiens.
目的 探讨中等量基底核区出血病人早期采用神经导航辅助下血肿穿刺抽吸联合尿激酶溶栓的优越性.方法 回顾性分析64例出血量在20~40 ml基底核区出血病人的临床资料,按手术方法不同分为两组,观察组采用神经导航辅助下血肿穿刺抽吸联合尿激酶溶栓治疗,对照组采用显微镜下微骨窗颞中回或外侧裂入路手术.对比两组治疗结果.结果 血肿清除率比较:术后1 d观察组明显低于对照组(P<0.05),而术后5 d两组无明显差异(P>0.05).水肿带体积比较:术后1 d两组无明显差异(P>0.05),术后5、10 d观察组比对照组明显减小(P<0.05).术后3周内并发症比较:观察组并发症发生率明显低于对照组(P<0.05).术后3个月ADL评分比较:两组无显著差异(P>0.05).结论 早期神经导航辅助下血肿穿刺抽吸联合尿激酶治疗中等量基底核区出血能减轻血肿周围水肿带,降低术后早期并发症,使病人更早进入康复阶段.
颅腔是密闭且空间有限的腔隙,任何部位发生病变或产生明显的占位效应均可引起脑组织正常位置改变并产生脑疝.持续增高的颅内压(ICP)可对颅内脑组织、神经及血管产生不可逆的损伤,并继发全身多脏器功能障碍.本文主要在早期通过有创方法监测患者ICP变化,降阶梯减压并术后管控ICP,对脑疝患者的预后具有极大的改善作用,对临床目标化管理ICP也具有重要的指导意义.
Objective To study the value of star weighted angiography (SWAN) in the diagnostic grading and prognostic evaluation of patients with brain DAI. Methods Fifty patients with brain DAI hospitalized in Department of Neurosurgery of Ji’nan Military General Hospital during 2013 January to 2015 March, were selected to receive 3.0T MRI, including sequences of T1WI、T2WI、FLAIR and SWAN. The number of the lesions and distributional characteristics in each sequence was analyzed. Furthermore, the correlativity of the grading and prognosis in patients with DAI in combination with GCS score and GOS score was also analyzed. Results (1) The detection rate of cerebral microbleeds through SWAN was significantly higher than that with the method of T1WI、T2WI and FLAIR. (2) SWAN detected lesion distribution, diffuse brain swelling and brain stem injury is closely related to the GCS score grading and GOS score. (3) The prognosis of DAI displayed polarization state, the higher grade of the GCS score, the lower of GOS score, and the greater value of the risk of death. Conclusion SWAN was a reliable method for the grading of clinical diagnosis and prognosis assessment in the patients of DAI after TBI, and the accuracy of diagnosis of DAI was second only to pathological diagnosis. Key words: Diffuse axonal injury; Star weighted angiography; Cerebral microbleeds; Glasgow coma scale; Glasgow outcome scale
目的 本文回顾性分析了 12 0例采用新型自动活检装置活检的病人 ,评价了Bar公司Magnum活检系统Autovac(2 1G)自动活检枪的应用价值。方法 采用CT导引定位取材 ,病理涂片和组织细胞切片相结合的方法 ,对三种活检方法的病理结果进行比较。结果 直接法 :诊断率 93 %~ 97 5 %。并列法 :90 %~ 10 0 %。共轴法 :90 %。结论 直接法更具有操作简单 ,定位准确 ,损伤小 ,并发症少 ,取材好 ,诊断率较高等优点。是值得应用的方法。