Although advancements have been made in the diagnosis and management of brain abscesses, associated morbidity and mortality remain substantial. Secondary brain abscesses following emergency craniotomy may aggravate primary brain injury and lead to increased disability and complications. This single-center retrospective study evaluated adult patients diagnosed with secondary brain abscesses between June 2015 and June 2025. A total of 47 patients were included, with a mean age of 54.6 ± 15.1 years, and 35 patients (74.5

Traumatic brain injury (TBI) can lead to secondary brain damage, with post-traumatic neuroinflammation being a crucial indicator of the condition's progression and a predictor of patient prognosis. However, effective, evidence-based pharmacotherapy targeting post-TBI neuroinflammation remains lacking. In our study, we show that the use of the mechanosensitive ion channel inhibitor GsMTx4 effectively alleviated neuronal apoptosis and neuroinflammation, thereby ameliorating abnormal neurological behaviors in mice following TBI. Transcriptomic analysis of the tissue surrounding the injury site indicated downregulation of the extracellular matrix(ECM) degradation and inflammation-related signaling pathways. Complementary metabolomic profiling revealed the metabolic signature and a reduced abundance of metabolites associated with inflammatory responses and ECM degradation after treatment. We speculate that GsMTx4 may modulate various proteases, thereby disrupting the ECM degradation-neuroinflammation feedback loop and ultimately attenuating the progression of neuroinflammation-driven secondary brain damage. Immunostaining and functional assays further confirmed that GsMTx4 treatment preserved ECM-related proteins. These findings suggest that GsMTx4 may offer a promising therapeutic approach for the management of secondary damage following TBI.

Previous studies have indicated that iron disorder, inflammation, and autophagy play an important role in traumatic brain injury (TBI). The triggering receptor expressed on myeloid cells 2 (TREM2), an immunoglobulin superfamily transmembrane receptor, is involved in inflammation. However, the role of TREM2 in modulating the microglia response in TBI has been rarely investigated. The present study aimed to investigate if the iron chelator deferoxamine (DFO) could ameliorate TBI through autophagy mediated by the TREM2. TBI was developed by the controlled cortical impact (CCI) mouse model and stretching of individual primary cortical microglia taken from the tissue of the rat brain. DFO was intraperitoneally used for intervention. Western blotting assay, qRT-PCR, TUNEL staining, immunofluorescence staining, confocal microscopy analysis, transmission electron microscopy, H&E staining, brain water content measurement, and the neurobehavioral assessments were performed. TREM2 expression was up-regulated in cortex of TBI mice model and in microglia stretching model, which was attenuated by DFO. After the mice were subjected to CCI, DFO treatment significantly up-regulated the protein levels of autophagy compared with the TBI group at 3 days and caused an increase of autophagic vacuoles. Treatment with DFO reduced TBI-induced cell apoptosis, cerebral edema, neuroinflammation, and motor function impairment in mice, at least partly via the mTOR signaling pathway that facilitates the TREM2 activity. The results indicated that the maintenance of iron homeostasis by DFO plays neuroprotection by modulating the inflammatory response to TBI through TREM2-mediated autophagy. This study suggested that TREM2-mediated autophagy might be a potential target for therapeutic intervention in TBI.

*These authors contributed equally to this work Background: Aggressive metastasis of tumor cells assumed a constructive role in strengthening chemoresistance of tumors, so this investigation was intended to elucidate if lncRNA CCAT2 sponging downstream miR-424 regulated chemotolerance of glioma cells by boosting metastasis of glioma cells. Methods: One hundred and twenty-eight pairs of glioma tissues and corresponding adjacent tissues were resected from glioma patients during their operation, and we also purchased a series of glioma cell lines, including U251, U87, A172 and SHG44. Furthermore, pcDNA3.1-CCAT2, si-CCAT2, miR-424 mimic and miR-424 inhibitor were transfected into SHG44 and U251 cell lines, so as to evaluate impacts of CCAT2 and miR-424 on chemosensitivity of the glioma cells. Besides, proliferation, invasion and metastasis of the cells were determined through the implementation of colony formation assay, transwell assay and scratch assay. Results: Glioma tissues and cells were monitored with higher CCAT2 expression and lower miR-424 expression than adjacent normal tissues and NHA cell line (P<0.05). Among the glioma cell lines, the SHG44 cell line showed the strongest resistance against teniposide, temozolomide and cisplatin (P<0.05), whereas the U251 cell line was more sensitive to teniposide, temozolomide, vincristine and cisplatin than any other cell line (P<0.05). Besides, pcDNA3.1-CCAT2 and miR-424 inhibitor could enhance tolerance of glioma cell lines against drugs (P<0.05). Moreover, in-vitro transfection of si-CCAT2 and miR-424 mimic could significantly retard proliferation, invasion and migration of SHG44 and U251 cells (P<0.05), and CCAT2 was found to negatively regulate miR-424 expression by sponging it (P<0.05). In addition, CHK1 was deemed as the molecule targeted by upstream miR424, and its overexpression can changeover the effects of miR-424 mimic on proliferation and metastasis of SHG44 and U251 cells. Conclusion: lncRNA CCAT2/miR-424/Chk1 axis might serve as a promising target for improving chemotherapeutic efficacies in glioma treatment.

Background Aggressive metastasis of tumor cells assumed a constructive role in strengthening chemoresistance of tumors, so this investigation was intended to elucidate if lncRNA CCAT2 sponging downstream miR-424 regulated chemotolerance of glioma cells by boosting metastasis of glioma cells. Methods One hundred and twenty-eight pairs of glioma tissues and corresponding adjacent tissues were resected from glioma patients during their operation, and we also purchased a series of glioma cell lines, including U251, U87, A172 and SHG44. Furthermore, pcDNA3.1-CCAT2, si-CCAT2, miR-424 mimic and miR-424 inhibitor were transfected into SHG44 and U251 cell lines, so as to evaluate impacts of CCAT2 and miR-424 on chemosensitivity of the glioma cells. Besides, proliferation, invasion and metastasis of the cells were determined through the implementation of colony formation assay, transwell assay and scratch assay. Results Glioma tissues and cells were monitored with higher CCAT2 expression and lower miR-424 expression than adjacent normal tissues and NHA cell line (P<0.05). Among the glioma cell lines, the SHG44 cell line showed the strongest resistance against teniposide, temozolomide and cisplatin (P<0.05), whereas the U251 cell line was more sensitive to teniposide, temozolomide, vincristine and cisplatin than any other cell line (P<0.05). Besides, pcDNA3.1-CCAT2 and miR-424 inhibitor could enhance tolerance of glioma cell lines against drugs (P<0.05). Moreover, in-vitro transfection of si-CCAT2 and miR-424 mimic could significantly retard proliferation, invasion and migration of SHG44 and U251 cells (P<0.05), and CCAT2 was found to negatively regulate miR-424 expression by sponging it (P<0.05). In addition, CHK1 was deemed as the molecule targeted by upstream miR-424, and its overexpression can changeover the effects of miR-424 mimic on proliferation and metastasis of SHG44 and U251 cells. Conclusion lncRNA CCAT2/miR-424/Chk1 axis might serve as a promising target for improving chemotherapeutic efficacies in glioma treatment.

Background Traumatic brain injury (TBI) is a common neurological emergency observed in hospitals. A considerable number of patients suffer from long-term disabilities after TBI. This study aimed to identify altered gene expression signatures and mechanisms related to TBI-induced chronic neuroinflammation and neurodegeneration. Methods An integrated analysis was performed using published RNA-sequencing studies to determine TBI-induced differentially expressed genes (DEGs). Based on the DEG data, functional annotation, signal-net, and transcription factor analyses were conducted to understand the mechanism of chronic neuroinflammation and neurodegeneration induced after TBI. Results Two datasets were obtained using the Gene Expression Omnibus database, of which, 6,513 DEGs were identified (6,464 upregulated and 49 downregulated). Positive regulation of biological process, positive regulation of cellular process, nucleus, and heterocyclic compound binding were Gene Ontology terms significantly enriched in post-TBI rat models. Leukocyte transendothelial migration, chemokine signaling pathway, neurotrophin signaling pathway, and longevity-regulating pathway were significantly enriched after TBI. With regard to the signal-net analysis, FOXO3, DGKZ and ILK were considered the most critical genes derived using high–betweenness centrality calculation. A total of 44 TFs, including FOXO1, SRY and KLF4, were predicted to play an important role in the upregulation of gene expression. Using integrated bioinformatics analysis, TBI was found to be associated with a significant inflammatory response and neurodegeneration. FOXO3, apolipoprotein (APOE), microtubule-associated protein tau (MAPT), and TREM2 were probably associated with the TBI pathological process. The mitochondrial electron transport chain may be associated with neurodegeneration in patients with TBI, serving as a potential therapeutic target.

Background.Traumatic brain injury (TBI) is a common neurological emergency observed in hospitals.A considerable number of patients suffer from long-term disabilities after TBI.This study aimed to identify altered gene expression signatures and mechanisms related to TBI-induced chronic neuroinflammation and neurodegeneration.Methods.An integrated analysis was performed using published RNA-sequencing studies to determine TBI-induced differentially expressed genes (DEGs).Based on the DEG data, functional annotation, signal-net, and transcription factor analyses were conducted to understand the mechanism of chronic neuroinflammation and neurodegeneration induced after TBI.Results.Two datasets were obtained using the Gene Expression Omnibus database, of which, 6513 DEGs were identified (6464 upregulated and 49 downregulated).Positive regulation of biological process, positive regulation of cellular process, nucleus, and heterocyclic compound binding were Gene Ontology terms significantly enriched in post-TBI rat models.Leukocyte transendothelial migration, chemokine signaling pathway, neurotrophin signaling pathway, and longevity-regulating pathway were significantly enriched after TBI.With regard to the signal-net analysis, FOXO3, DGKZ, and ILK were considered the most critical genes derived using high-betweenness centrality calculation.A total of 44 TFs, including FOXO1, SRY, and KLF4, were predicted to play an important role in the upregulation of gene expression.Using integrated bioinformatics analysis, TBI was found to be associated with a significant inflammatory response and neurodegeneration.FOXO3, apolipoprotein (APOE), microtubule-associated protein tau (MAPT), and TREM2 were probably associated with the TBI pathological process.The mitochondrial electron transport chain may be associated with neurodegeneration in patients with TBI, serving as a potential therapeutic target.

BACKGROUND This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT). MATERIAL AND METHODS A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T10-T11 vertebral levels. Then, EA group rats received EA treatment. Reverse transcription polymerase chain reaction was used to detect NTFs and receptors at the mRNA level. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the expression of NTFs and their receptors. Basso, Beattie, Bresnahan (BBB) scores and cortical somato-sensory evoked potentials (CSEP) were evaluated to assess the recovery of motor and sensory functions. We also measured BDA (Biotinylated dextran amine) axonal tracing, CGRP (Calcitonin gene-related peptide), GAP-43 (Growth-associated protein), and synaptophysin immunohistochemistry (IHC). RESULTS EA treatment led to obvious improvement in hindlimb locomotor and sensory functions. CNTF, FGF-2, and TrkB mRNA were significantly upregulated, while NGF, PDGF, TGF-b1, IGF-1, TrkA, and TrkC mRNA were concomitantly downregulated in the caudal spinal segment (CSS) following EA. Immunohistochemistry demonstrated an increased number of CGRP fibers, GAP-43, and synaptophysin profiles in the CSS in the EA rats. CONCLUSIONS EA may promote the recovery of neuroplasticity in rats subjected to SCT. This could be attributed to the systematic regulation of NTFs and their receptors after EA.

Objetive To investigate the mechanism of fibroblast growth factor( b FGF)- modified bone marrow mesenchymal stem cells( BMSC) transplantation on functional recovery of glial fibrillary acidic protein after traumatic brain injury. Methods After isolation and culture,BMSCs were modified by adenovirus mediated transfection fibroblast growth factor between gene. Rat craniocerebral injury model were established using Feeney’s method,then randomized into control group,BMSC group and FGF- BMSC group. Using immunohistochemical method to detect Brd U labeled between BMSC in the brain tissue distribution and quantity of TUNEL method to detect apoptosis of brain cells. Results Cultivate BMCSs,Western- blot results showed that FGF gene was successfully transferred to the adenovirus vector. Brd U markers of FGF- BMSC group was significantly higher than BMSC group( P < 0. 05),and apoptotic cell number decreased significantly( P < 0. 05). After transplant 14 days,FGF- BMSC group in rats of Longa method between nerve function score significantly lower than the control group and BMSC group( P < 0. 05).Conclusion FGF- modified BMCS can improve the craniocerebral injury rats nerve function damage.

Rho-kinase dimerization is essential for its kinase activity and biological function; disruption of the dimerization has recently been established as a new and promising therapeutics strategy for cerebrovascular malformation (CM). Based on Rho-kinase dimer crystal structure we herein combined in silico analysis and in vitro assay to rationally derive self-inhibitory peptides from the dimerization interface. Three peptides namely Hlp1, Hlp2 and Hlp3 were successfully designed that have potential capability to rebind at the dimerization domain of Rho-kinase. Molecular dynamics (MD) simulations revealed that these peptides are helically structured when bound to Rho-kinase, but exhibit partially intrinsic disorder in unbound state. Binding free energy (BFE) analysis suggested that the peptides have a satisfactory energetic profile to interact with Rho-kinase. The computational findings were then substantiated by fluorescence anisotropy assays, conforming that the helical peptides can bind tightly to Rho-kinase with affinity KD at micromolar level. These designed peptides are considered as lead molecular entities that can be further modified and optimized to obtain more potent peptidomimetics as self-competitors to disrupt Rho-kinase dimerization in CM.

Background: Glioblastoma (GBM) is the most malignant nervous system tumor with an almost 100 % recurrence rate. Thymopoietin (TMPO) has been demonstrated to be upregulated in various tumors, including lung cancer, breast cancer, and so on, but its role in GBM has not been reported. This study was aimed to determine the role of TMPO in GBM.Methods: Publicly available Oncomine dataset analysis was used to explore the expression level of TMPO in GBM specimens. Then the expression of TMPO was knocked down in GBM cells using lentiviral system, and the knockdown efficacy was further validated by real-time quantitative PCR and western blot analysis. Furthermore, the effects of TMPO silencing on GBM cell proliferation and apoptosis were examined by MTT, colony formation, and flow cytometry analysis. Meanwhile, the expression of apoptotic markers caspase-3 and poly(ADP-ribose) polymerase (PARP) were investigated by western blot analysis.Results: This study observed that the expression of TMPO in GBM specimens was remarkably higher than that in normal brain specimens. Moreover, knockdown of TMPO could significantly inhibit cell proliferation and arrest cell cycle progression at the G2/M phase. It also found that TMPO knockdown promoted cell apoptosis by upregulation of the cleavage of caspase-3 and PARP protein levels which are the markers of apoptosis.Conclusions: The results suggested TMPO might be a novel therapeutic target for GBM.

Neuronal polo-like kinase (nPLK) is an essential regular of cell cycle and differentiation in nervous system, and targeting nPLK has been established as a promising therapeutic strategy to treat neurological disorders and to promote neuroregeneration. The protein contains an N-terminal kinase domain (KD) and a C-terminal Polo-box domain (PBD) that are mutually inhibited by each other. Here, the intramolecular KD-PBD complex in nPLK was investigated at structural level via bioinformatics analysis, molecular dynamics (MD) simulation and binding affinity scoring. From the complex interface two regions representing separately two continuous peptide fragments in PBD domain were identified as the hot spots of KD-PBD interaction. Structural and energetic analysis suggested that one (PBD peptide 1) of the two peptides can bind tightly to a pocket nearby the active site of KD domain, which is thus potential as self-inhibitory peptide to target and suppress nPLK kinase activity. The knowledge harvesting from computational studies were then used to guide the structural optimization and mutation of PBD peptide 1. Consequently, two of three peptide mutants separately exhibited moderately and considerably increased affinity as compared to the native peptide. The computationally modeled complex structures of KD domain with these self-inhibitory peptides were also examined in detail to unravel the structural basis and energetic property of nPLK-peptide recognition and interaction.

目的 探讨去铁胺(D FX)对大鼠脑外伤急性期半影区脑红蛋白(Ngb)表达及损伤灶的影响.方法 90只SD大鼠随机分为假手术组、实验组和对照组,每组30只.实验组和对照组大鼠分别建立控制性皮质撞击模型,假手术组开颅而不致伤.实验组大鼠伤后2、6h经腹腔注射DFX(100 mg/kg),此后每12 h给药1次;对照组大鼠在相同时间点经腹腔注射等量生理盐水.各组大鼠分别于术后6、12、24、48 h取6只断头取脑,RT-PCR及Western-blotting检测损伤半影区脑组织Ngb表达.伤后3d,每组各取6只大鼠行3.0T磁共振成像(MRI)检查,选T2序列计算损伤灶体积.结果 损伤半影区脑组织Ngb mRNA和蛋白表达在伤后早期显著增高,分别在12h和24 h达高峰,随后缓慢下降,直到伤后48 h仍维持较高的表达水平.与对照组比较,实验组大鼠伤后12、24、48 h的Ngb mRNA和蛋白表达明显上调,伤后3d损伤灶体积较小.结论 DFX在脑外伤急性期有脑保护作用,能缩小损伤灶体积,其保护作用可能与诱导内源性脑保护因子Ngb的表达有关.

BACKGROUND:This study aimed to evaluate the usability of SWI in assessment of brain iron to detect cognitive dysfunction in patients with chronic mild traumatic brain injury (mTBI).METHODS:39 patients with mTBI and 37 normal controls were given the Mini-Mental State Examination (MMSE) and underwent SWI scanning at least 6 months after injury. Angle radian values were calculated with phase images. The angle radian values were compared between groups using analysis of covariance, and their association with MMSE scores was analyzed using Spearman correlations.RESULTS:Significantly higher angle radian values (p < 0.05) were found in the head of the caudate nucleus, the lenticular nucleus, the hippocampus, the thalamus, the right substantia nigra, the red nucleus, and the splenium of the corpus callosum (SCC) in the mTBI group, compared to the control group. MMSE scores were negatively correlated with angle radian values in the right substantia nigra (r = -0.685, p < 0.001).CONCLUSIONS:Patients with chronic mTBI might have abnormally high accumulations of iron, and their MMSE scores are negatively associated with angle radian values in the right substantia nigra, suggesting a role of SWI in the assessment of cognitive impairments of these patients.

OBJECTIVE The Cycle of Willis unites the internal carotid and vertebrobasilar system and maintains the stability of blood supply to the brain. This present study aims to analyze the anatomic variations in the anterior part of the Cycle of Willis. METHODS Forty five formalin-preserved human brains (90 cerebral hemispheres) with intact dura mater from Chinese adults were dissected under the surgical microscope. The anterior components of the Circle of Willis were observed and measured. Anatomic variations of this segment were observed and photographed. The data collected in this investigation was statistically analyzed. RESULTS In approximately 13.3% (6/45) of all cerebral samples, a caliber difference of ≥ 0.5 mm was noted between the left A1 and the right segments. The A2 segments of left and right hemispheres were derived from the contralateral A1 segment in 6.7% (3/45) of the brain specimens. Simple anterior communicating artery (ACoA) was observed in 37.8% (17/45) whereas complex ACoA was noted in 60% (27/45) of cerebral samples. CONCLUSION As it demonstrates the anatomic variations of ACAC, all surgical approaches should be performed after angiographic demonstrations. Understanding of these anatomic variations plays a pivotal role in neurovascular procedures.

Objective: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis.Methods: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed.Results: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient's GCS score on admission (p<0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p<0.05).Conclusions: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

Both delayed posttraumatic intracerebral hemorrhage and epidural hematoma have been well described in the neurosurgical literatures. However, delayed posttraumatic acute subdural hematoma which happens more than a week with a rapid progress after mild traumatic brain injury and causes death of patient is rarely reported. We show two such cases and briefly review the literature and discuss the probable pathogenesis of their rapid progress.

Aim: To study the variation in microsurgical anatomy of posterior circulation of the Circle of Willis in Chinese adult population to provide anatomical guide for high-risk vascular and cranial base surgery. Methods: Forty-six Chinese adult cadaveric brain specimens fixed in formalin were dissected, examined, measured, and photographed under light microscopy. Results: Over 60% of the posterior communicating arteries (PCoAs) in 46 cases (92 samples, both sides) were found to have differences in diameter between the 2 sides. About 50% of cases showed variation in length of >2 mm. Approximately 50% of the samples appeared to have a normal anatomic relationship between posterior communicating artery and the posterior cerebral artery (PCA). The occurrence rate of perforating branches from the precommunicating segment of the PCA (P1) was 98%. The angle of the basilar artery with bilateral PCA was measured as 45 to 150 degrees (mean 105 degrees). Conclusions: Variation in diameter, length, and/or other anatomic factors occurred in more than 50% of cases in the posterior circulation of the Circle of Willis.

Methylenetetrahydrofolate reductase (MTHFR) gene plays key roles not only in folate metabolism but also in carcinogenesis. The single nucleotide polymorphism MTHFR C677T has been indicated in the development of various tumors. The effect of the MTHFR C677T polymorphism on brain tumors remains poorly understood. We performed the present meta-analysis and aimed to provide a better understanding of the pathogenesis of brain tumors. A literature search of the PubMed, Embase, Web of Science, and Wanfang databases was carried out for potential relevant publications. We calculated the pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) to assess the association of MTHFR C677T with the susceptibility to brain tumors. We also performed stratified analysis and sensitivity analysis to further estimate the genetic association. All statistical analyses were conducted by the use of STATA 11.0 (STATA Corporation, College Station, TX, USA). Eight case-control studies involving a total of 3,059 cases and 3,324 controls were retrieved according to the inclusion criteria. The overall ORs suggested that the MTHFR C677T variant can exert a risk effect on brain tumor development under the following contrast models (OR(TC vs. CC) = 1.14, 95% CI 1.02-1.27, P OR = 0.018; OR(TT + TC vs. CC)= 1.23, 95% CI 1.01-1.51, P(OR) = 0.043). No significant correlation was identified among the Caucasians, but not among the Asians. In addition, the TC genotype carriers were more susceptible to meningioma when compared with the CC genotype carriers (OR(TC vs. CC) = 1.38, 95% CI 1.15-1.65, P(OR) < 0.001). The MTHFR C677T polymorphism seemed to exert no effect on glioma risk. The current meta-analysis firstly provides evidence that the MTHFR C677T polymorphism may modify the risk for brain tumors, particularly meningioma. The role of the MTHFR C677T variant in brain tumor pathogenesis across diverse ethnicities needs further elucidation by more future studies with large sample size.