Assessment of cerebrovascular alterations induced by inflammatory response and oxidative-nitrative stress after traumatic intracranial hypertension and a potential mitigation strategy.

The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.

Clinical and imaging characteristics of growing skull fractures in children.

Growing skull fracture (GSF) is an uncommon form of head trauma among young children. In prior research, the majority of GSFs were typically classified based on pathophysiological mechanisms or the duration following injury. However, considering the varying severity of initial trauma and the disparities in the time elapsed between injury and hospital admission among patients, our objective was to devise a clinically useful classification system for GSFs among children, grounded in both clinical presentations and imaging findings, in order to guide clinical diagnosis and treatment decisions. The clinical and imaging data of 23 patients less than 12 years who underwent GSF were retrospectively collected and classified into four types. The clinical and imaging characteristics of the different types were reviewed in detail and statistically analyzed. In all 23 patients, 5 in type I, 7 in type II, 8 in type III, and 3 in type IV. 21/23 (91.3%) were younger than 3 years. Age ≤ 3 years and subscalp fluctuating mass were common in type I-III (P = 0.026, P = 0.005). Fracture width ≥ 4 mm was more common in type II-IV (P = 0.003), while neurological dysfunction mostly occurred in type III and IV (P < 0.001).Skull "crater-like" changes were existed in all type IV. 10/12 (83.3%) patients with neurological dysfunction had improved in motor or linguistic function. There was not improved in patients with type IV. GCS in different stage has its unique clinical and imaging characteristics. This classification could help early diagnosis and treatment for GCS, also could improve the prognosis significantly.

Biomarkers for predicting the severity of spinal cord injury by proteomic analysis.

Purpose: Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity. Methods: SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay. Results: After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM. Conclusion: Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.

Acute subdural haematoma exacerbates cerebral blood flow disorder and promotes the development of intraoperative brain bulge in patients with severe traumatic brain injury.

BACKGROUND: Decompressive craniectomy (DC) is a routine procedure used for the treatment of severe traumatic brain injury (TBI) with concomitant acute subdural haematoma (SDH). However, certain patients are prone to developing malignant brain bulge during DC, which prolongs the operative time and worsens patient outcomes. Previous studies have shown that malignant intraoperative brain bulge (IOBB) may be associated with excessive arterial hyperaemia caused by cerebrovascular system disorders. Through a clinical retrospective analysis and prospective observations, we found that the cerebral blood flow of patients who possessed risk factors manifested high resistance and low flow velocity, which severely affected brain tissue perfusion and resulted in the occurrence of malignant IOBB. In the current literature, rat models of severe brain injury-associated brain bulge have rarely been reported. METHODS: To gain an in-depth understanding of cerebrovascular changes and the cascade of responses related to brain bulge, we introduced acute SDH into the Marmarou model for the preparation of a rat model of high intracranial pressure (ICP) to simulate the pathological conditions experienced by patients with severe brain injury. RESULTS: With the introduction of a 400-µL haematoma, significant dynamic changes occurred in ICP, mean arterial pressure, and relative blood perfusion rate of the cerebral cortical vessels. ICP increased to 56.9 ± 2.3 mmHg, mean arterial pressure showed reactive decrease, and the blood flow of cerebral cortical arteries and veins on the non-SDH-affected side decreased to < 10%. These changes could not fully recover even after DC. This resulted in generalised damage to the neurovascular unit and a lag effect to the venous blood reflux, which triggered malignant IOBB formation during DC. CONCLUSION: An excessive increase in ICP causes cerebrovascular dysfunction and brings about a cascade of damage to brain tissue, which forms the basis for the development of diffuse brain swelling. The subsequent heterogeneous responses of the cerebral arteries and veins during craniotomy may be the main cause of primary IOBB. Clinicians should pay particular attention to the redistribution of CBF to various vessels when performing DC in patients with severe TBI.

Computational analysis and verification of molecular genetic targets for glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with a poor prognosis. The initial treatment for high-grade gliomas is surgical excision. However, even with concomitant use of radiation or chemotherapy, patients are still prone to recurrence. The specific pathogenesis of GBM is still controversial. METHODS: Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between GBM and normal brain tissues were screened. P-value was obtained by Bayes test based on the limma package. Statistical significance was set as P-value <0.05 and |Fold change (FC)| > 0.2 (GSE90886); P-value <0.05 and |FC| > 1 (GSE116520, GSE103228). Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network were performed. Hub genes were selected from miRNA target genes and DEGs. GBM and normal brain tissues were extracted to verify the expression. RESULTS: A total of 100 DEGs were overlapped in both datasets. Analysis of pathways and process enrichment tests indicated that ion transport, positive regulation of macromolecule metabolic process, cell cycle, axon guidance were enriched in the GBM. Sixteen hub genes were identified. Hub genes ADARB1 and neuropilin 1 (NRP1) were significantly associated with overall survival (OS) and disease-free survival (DFS) (P<0.05). Eukaryotic translation termination factor 1 (ETF1) was associated with DFS (P<0.05). CONCLUSIONS: DEGs and DEMs were found between GBM tumor tissues and normal brain tissues. These biomarkers may be used as targets for early diagnosis and specific treatment.

Lateral Craniopharyngeal Canal: An Anatomical Cause of Spontaneous Rhinorrhea.

The aim of this report is to investigate the pathogenesis and surgical treatment of encephalocele located in the sphenoid sinus and presented with spontaneous rhinorrhea. The data of a patient with sphenoid sinus encephalocele was analyzed in association with the review of literature. The patient admitted to our clinic with rhinorrhea from the left nasal cavity. Cranial magnetic resonance imaging revealed bone defects in the left sphenoid sinus wall, and the presence of brain tissue and cerebrospinal fluid (CSF) in the sphenoid sinus. The patient underwent dural repair via left pterional approach. Rhinorrhea disappeared after surgery. The pathogenesis of the encephalocele in the sphenoid sinus is not clear. It may be related to the presence of lateral craniopharyngeal canal, extra-gasification in the sphenoid sinus, high intracranial pressure or other factors. It is very important to diagnose accurately the source of CSF fistula in preoperative period, choose the specific operation technique, and follow-up the patient for a long time period.

Olfactory function and quality of life following microscopic endonasal transsphenoidal pituitary surgery.

Olfactory outcomes as well as oronasal postoperative complications of transsphenoidal pituitary surgery have not been well studied. The objective of this study was to investigate nasal symptoms including olfactory function as well as quality of life following transsphenoidal pituitary surgery. The study is designed as a prospective cohort study set in a single tertiary hospital. A total of 53 patients with pituitary adenomas were included. All patients underwent pituitary surgery with the right-sided endonasal transsphenoidal approach. Outcomes were assessed with the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36) to survey patient health, the Chinese version of the 22-item Sinonasal Outcome Test (SNOT-22), and a Toyota and Takagi (T&T) olfactometer. Assessments were carried out before surgery and at 1 week, and 1 and 4 months after surgery. The overall SF-36 scores were significantly lower, but the SNOT-22 scores were higher at 1 week and 1 month postoperatively compared with baseline (all P < 0.001). The results of T&T olfactometer testing showed that there was a significant decline in the ability to detect odors postoperatively, even at 4 months. Multivariate linear regression analysis showed that lower education level, partial tumor removal, and longer duration of surgery were independent risk factors for a higher SNOT-22 score at 1 week after surgery. The findings show that microscopic endonasal transsphenoidal pituitary surgery impairs olfactory function in most patients for at least 4 months after surgery.