Superficial meningioma with bone involvement: surgical strategies and clinical outcomes.

INTRODUCTION: Meningiomas with bone involvement account for 4.5-17% of all intracranial meningiomas. Little is known about whether these meningiomas (WHO grade I) behave differently than meningiomas without bone involvement. We sought to study the relatively uncommon imaging manifestations of meningioma and to evaluate their clinical significance. METHODS: A single-institution retrospective cohort study of surgically treated superficial meningioma patients between 2011 and 2022 was conducted. Age, sex, preoperative imaging, operative data, and surgical outcomes were reviewed. Imaging variables and outcomes were reported for patients with bone-invading meningiomas and compared with those with nonbone-invading meningiomas. Univariate analyses were also conducted. RESULTS: Of 577 total superficial meningiomas treated surgically, 47 (8.1%) exhibited bone invasion. Most bone-invading meningiomas were parasagittal (n = 29, 61.7%). A total of 12.7% (n = 6) of patients with bone-invading meningioma had recurrence, whereas 9.1% (n = 48) of patients with non-bone-invading meningioma had recurrence (p = 0.426). No significant difference in the median time to recurrence was observed between patients with bone-invading meningiomas and patients with nonbone-invading meningiomas (69.8 months, Q1:53.1; Q3:81.4 months vs. 69.7 months, Q1:47.5; Q3:96.7; p = 0.638). CONCLUSIONS: Superficial meningioma with bone involvement had similar outcomes compared to those of superficial meningioma without bone involvement. Hyperostosis in meningioma (WHO grade I) may not be a surrogate for aggressive meningioma behavior.

Lung cancer brain metastasis and hemorrhagic cerebral venous thrombosis: experiences and lessons.

The incidence of lung cancer brain metastasis combined with hemorrhagic cerebral venous sinus thrombosis (CVST) is very rare, and the understanding and treatment experience of this case is insufficient. We reported a case of lung cancer brain metastasis accompanied by venous sinus thrombosis, and describe the diagnosis and treatment plan for colleagues to learn from experience and lessons.

Preoperative antiepileptic drug prophylaxis for early postoperative seizures in supratentorial meningioma: a single-center experience.

OBJECTIVE: Perioperative antiepileptic drug (AED) prophylaxis for early postoperative seizures (EPSs) in patients with supratentorial meningiomas without preoperative seizures is controversial. This paper discusses the incidence, risk factors, control rate and AED withdrawal indications of EPS in patients undergoing supratentorial convexity and parasagittal/falx meningioma resection without preoperative seizures. METHODS: Patients treated for a histologically confirmed supratentorial convexity and parasagittal/falx meningioma at the authors' institution between 2015 and 2021 were retrospectively examined. Clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate regression analyses. A PubMed review of the literature published between 2011 and 2021 was performed. RESULTS: In total, 517 patients met the selection criteria. EPS (within the first postoperative week) was observed in 30/517 cases (5.8%). Multivariate analysis revealed that surgical/medical complications (OR 16.33, 95% CI 7.07-37.7, P < 0.001) were the only independent predictors of EPS. The dose of valproic was increased and levetiracetam was added based on the frequency of seizures (≤ 2, > 2 times and status epilepticus). EPS control rates were 94.1% (16/17) and 92.3% (12/13), respectively. AEDs were discontinued at 2 weeks and 4-6 weeks, respectively. The authors identified 10 relevant studies in the literature. Based on their review of the literature, the incidence of EPS was 3.7% (47/1282) with AED use and 6.2% (95/1525) without AED use patients in supratentorial meningiomas without preoperative seizures. The incidence of EPS was 9.0% (19/209) in patients without AED use with convexity and parasagittal/falx meningiomas without preoperative seizures. CONCLUSIONS: AED prophylaxis can reduce the incidence of EPS in patients with convexity and parasagittal/falx meningiomas without preoperative seizures. Avoiding postoperative complications is an important means to prevent EPS. Combined medication has a significant effect on controlling repeated EPS. The timing of AED withdrawal was evaluated according to the clinical symptoms and imaging findings.

Analysis of Long-Term Prognosis and Prognostic Predictors in Severe Brain Injury Patients Undergoing Decompressive Craniectomy and Standard Care.

Decompressive craniectomy (DC) is widely used to treat acute subdural haematoma and hemispheric swelling following traumatic brain injury (TBI). The therapeutic effect of DC on severe TBI treatment is still controversial. The aim of our study was to evaluate effectiveness of DC treatment and seek some prognostic predictors. According to the therapy method, we divided the patients into 2 groups: DC group and standard care group. Between 2010 and 2014, a total number of 223 severe TBI patients, containing 112 patients undergoing DC and 111 patients undergoing standard care, were enrolled into the study according to Glasgow Coma Scale (GCS). The long-term prognosis was evaluated by Extended Glasgow Outcome Scale 12 months after discharging from hospital. We used univariate analysis and receiver operating characteristic curves to explore prognostic predictors. The results showed that patients in the DC group had a lower mortality, but there was no statistical significance in long-term prognosis between these 2 groups. It seemed that admission GCS, platelet, neutrophile granulocyte, total protein, and albumin were associated with long-term prognosis in DC group and reactivity of pupils in standard care group. Simultaneously, using the multivariable logistic regression model, we confirmed that admission GCS and albumin were independent prognostic predictors for patients undergoing DC, and reactivity of pupils for those undergoing standard care. Our data suggested that DC was an effective therapy for severe TBI patients in reducing mortality, but it failed to improve long-term prognosis. Through our study, we could comprehend the characteristics of the 2 treatments and provide more scientific individuation therapy for severe TBI patients.

Hemorrhagic cerebral venous infarction after vein injury during intraoperative lesion resection: incidence, hemorrhagic stages, risk factors and prognosis.

Objective: Cerebral venous infarction (CVI) after vein injury during intraoperative lesion resection is associated with intracranial hemorrhage. We conducted this study to identify the incidence, clinical and imaging features, and prognosis of hemorrhage CVI. Methods: We performed a retrospective analysis of patients with confirmed CVI after vein injury who underwent craniotomy in our hospital. Postoperative clinical symptoms were observed, and imaging features were compared between patients with and without intracranial hemorrhages through CT examination. Variables were analyzed using univariate and multivariate regression analyses. Results: Among 2,767 patients who underwent craniotomy, 93 cases of injured veins were identified intraoperatively. Hemorrhagic CVI was found in 38% (35/93). Multivariate analysis revealed that midline approach, meningioma, postoperative seizures, disorders of consciousness and interval in hours < 72 h were identified as predictors of hemorrhagic CVI. After 3 months of follow-up, the prognosis was poor in 15 cases (16%, 15/93), including death (two cases), vegetative survival (four cases), and severe disability (nine cases). Conclusions: Hemorrhagic CVI, as a critical complication after venous injury, can have disastrous consequences. Do not injure known veins intraoperatively. In case of injury, requisite remedial measures should be adopted during and after surgery.

Relationship Between Evolutionary Diversity and Aboveground Biomass During 150 Years of Natural Vegetation Regeneration in Temperate China.

While the link between plant species diversity and biomass has been well-studied, the impact of evolutionary diversity on community biomass across long timescales or ongoing change remains a subject of debate. We elucidated the association between evolutionary diversity and community aboveground biomass (AGB) using an ideal experimental system with over 150-year history of natural vegetation regeneration. Higher phylogenetic diversity facilitated the sampling effect under the influence of environmental filtering, and caused an increase in AGB. Phylogenetic structure varied from aggregation to dispersion during the later period of vegetation recovery (70-150 years), which was correlated with increases in niche complementarity and increasing AGB. Woody plant evolutionary diversity was used as a key to predict the relationship between vegetation recovery and AGB, with a total explanatory power of ~84.7%. Mixed forests composed of evergreen conifers and deciduous broadleaf forests had higher carbon sequestration potential than that of pure forests, which is advantageous for increasing top-stage AGB. This research expands our knowledge of the causes and effects of biodiversity and ecosystem function dynamics over time and space, which is important for accurately predicting future climate change effects.

Precise location of the ventricular catheter tip in ventriculoperitoneal shunt placement guided by 3D printed individualized guide.

OBJECTIVE: Improper placement of the ventricular catheter tip is the most common cause of shunting disorders after ventriculoperitoneal shunt (VPS) placement surgery. Here, through two illustrative cases, we described a novel method of precise ventricular catheter tip location. METHODS: Three-dimensional (3D) Slicer software was used to define the ventricle puncture path and determine the ventricle catheter tip location preoperatively, and the 3D individualized guide model was printed. RESULTS: The ventricular puncture was performed under the guidance of the 3D guide to achieve precise ventricle catheter tip location intraoperatively. CONCLUSIONS: This technique is safe, simple, efficient and cost-effective, which facilitates its clinical implementation and promotion.

Salvation of Temporalis Muscle in Cranioplasty: A Technique Note.

OBJECTIVE: The preservation of the temporalis muscle during cranioplasty is very important for postoperative masticatory function and aesthetics. The key technique for temporalis muscle preservation is to find the surgical plane during the operation. METHODS: In the past, the so-called antiadhesion method could not be used to find the surgical plane very well. Here, we describe a novel method for separating the temporalis muscle and dura through an illustrative case, utilizing the natural space of the temporalis muscle at the bony border attachment point. RESULTS: The temporalis muscle is stretched by a wire saw to find the surgical plane quickly and accurately, maximizing the preservation of the temporalis muscle without damaging the dura. CONCLUSIONS: The technical effect is ideal, the operation is simple, and the technique is suitable for promotion.

Analysis of risk factors and treatment strategies for lumbar cistern blockage after craniocerebral surgery.

Objective: Lumbar cistern blockage is a common complication of continuous lumbar cistern drainage. This paper analyzes the risk factors for lumbar cistern blockage drainage due to various causes and proposes a series of prevention and intervention measures to reduce blockage or improve recanalization after blockage. Methods: The clinical data of 637 patients with various lesions who underwent lumbar cistern drainage in our hospital were retrospectively collected and analyzed. Perioperative clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate logistic regression analyses. Results: A total of 13.7% (87/637) of patients had lumbar cistern blockage. Multivariate analysis revealed that drainage time (≥7 days), CSF volume <200 (mL/d), CSF leakage, and abnormal CSF properties were predictors of lumbar cistern blockage. Reducing the probability of lumbar cistern blockage can be achieved by repeatedly flushing, increasing the drainage flow and shortening the drainage time. The recanalization rate after blockage was 67.8% (59/87). After the drainage tube was removed, no complications related to the drainage tube occurred during the 1-week follow-up. Conclusion: Lumbar cistern blockage is the main reason for poor drainage. Prevention or early intervention can effectively reduce the probability of blockage and achieve the purpose of drainage of cerebrospinal fluid.

Plant diversity drives soil carbon sequestration: evidence from 150 years of vegetation restoration in the temperate zone.

Large-scale afforestation is considered a natural way to address climate challenges (e.g., the greenhouse effect). However, there is a paucity of evidence linking plant diversity to soil carbon sequestration pathways during long-term natural restoration of temperate vegetation. In particular, the carbon sequestration mechanisms and functions of woody plants require further study. Therefore, we conducted a comparative study of plant diversity and soil carbon sequestration characteristics during 150 years of natural vegetation restoration in the temperate zone to provide a comprehensive assessment of the effects of long-term natural vegetation restoration processes on soil organic carbon stocks. The results suggested positive effects of woody plant diversity on carbon sequestration. In addition, fine root biomass and deadfall accumulation were significantly positively correlated with soil organic carbon stocks, and carbon was stored in large grain size aggregates (1-5 mm). Meanwhile, the diversity of Fabaceae and Rosaceae was observed to be important for soil organic carbon accumulation, and the carbon sequestration function of shrubs should not be neglected during vegetation restoration. Finally, we identified three plants that showed high potential for carbon sequestration: Lespedeza bicolor, Sophora davidii, and Cotoneaster multiflorus, which should be considered for inclusion in the construction of local artificial vegetation. Among them, L. bicolor is probably the best choice.

[Carbon Sequestration Characteristics Under Natural Vegetation Restoration in Ziwuling Area of the Loess Plateau].

The aim of this study was to analyze the carbon sink effect under natural vegetation restoration and the influence of changes in vegetation community characteristics on ecosystem carbon density in ecologically fragile areas of the Loess Plateau. In this study, the changes in carbon sequestration of a vegetation-soil system under eight successional stages[slope cropland, abandoned cropland for 10 years, abandoned cropland for 20 years, Sophora davidii (Franch.) Skeels., Betula platyphylla Suk., Pinus tabulaeformis Carr., Quercus wutaishanic Mary+P. tabulaeformis Carr mixed forests, and Q. wutaishanic Mary] in Ziwuling area over 150 restoration periods were investigated using the common method of spatial and temporal substitution. This study also discussed the relationship between changes in vegetation community characteristics and vegetation-soil system carbon density. The results showed that the community coverage of the investigated vegetation fluctuated from 85% in the slope cropland stage to 100% in the arbor stage. The number of species, Margalef index, Shannon-Wiener index, Pielou index, and Simpson index initially increased rapidly, then declined slowly until becoming stable, and reached a peak in the middle of the succession (B. platyphylla Suk.). The biomass and carbon density of vegetation components (above-ground biomass, below-ground roots, and litter) increased exponentially during the succession, i.e., increased slowly before B. platyphylla Suk. but increased significantly in B. platyphylla Suk. and P. tabulaeformis Carr.(P<0.05). The biomass and carbon density reached the maximum values of 27858.08 g·m-2 and 13232.51 g·m-2, respectively, in Q. wutaishanic Mary+P. tabulaeformis Carr mixed forests and tended to be stable in the late succession stage. Soil organic carbon density showed a power function relationship with vegetation restoration, with the greatest increase in the stages of abandoned cropland for 10 years and B. platyphylla, but no significant changes in the subsequent stages (P>0.05). In the early succession stage, the carbon density of the farmland ecosystem was the lowest (4395.70 g·m-2), whereas the other seven stages increased by 55.54%, 40.37%, 69.96%, 202.48%, 326.35%, 357.43%, and 351.07%, respectively, compared with the farmland ecosystem. Community coverage, Margalef index, Shannon-Wiener index, above-ground biomass, root biomass, and litter biomass were significantly positively correlated with vegetation-soil system carbon density (P<0.05). The carbon sink effect of long-term natural restoration in Ziwuling Region was significant, and the carbon density of the vegetation-soil system under interspecific competition tended to be stable in the late succession stage. Dynamic changes in the vegetation community structure and plant diversity during the succession process increased vegetation carbon density and soil carbon density. This study helps to clarify the carbon sink effect of natural vegetation restoration in ecologically fragile areas of the Loess Plateau and provides a theoretical basis for promoting natural forest conservation and achieving carbon neutrality.

Duraplasty with autologous nuchal ligament fascia to reduce postoperative complications in pediatric patients undergoing neoplasia resection with a suboccipital midline approach.

OBJECTIVE: The authors sought to explore the safety and efficacy of an autologous nuchal ligament for dural repair in pediatric patients undergoing tumor resection through a suboccipital midline approach. METHODS: Pediatric patients diagnosed with posterior fossa neoplasia who underwent surgery through a suboccipital midline approach were retrospectively reviewed. The patients were divided into artificial graft and autograft groups according to whether artificial duraplasty material or autologous nuchal ligament was used to repair the dura. Postoperative complications were reviewed and analyzed, including CSF leak, pseudomeningocele, and meningitis, during hospitalization and follow-up. Univariate and multivariate logistic regression analyses were used to investigate the relationship between duraplasty material and postoperative complications, as well as other risk factors for postoperative complications. Furthermore, multinomial logistic regression analysis was used to clarify which postoperative complications the autologous nuchal ligament tended to reduce. RESULTS: This retrospective study included 66 pediatric patients who underwent tumor resection through a suboccipital midline approach. The clinical baseline characteristics were comparable between the two groups. The results showed that the autograft group had significantly fewer postoperative complications, especially pseudomeningocele, compared with the artificial graft group. Moreover, the time required to repair the dura in the autograft group was significantly less than that in the artificial graft group. Further results revealed that the duraplasty material, ependymoma, preoperative severe hydrocephalus requiring an external ventricular drain (EVD), and postoperative hydrocephalus exacerbation were independent risk factors for postoperative complications. In particular, the autologous fascia of the nuchal ligament tended to reduce pseudomeningocele more than CSF leak and meningitis. However, compared with pseudomeningocele and CSF leak, both ependymoma and postoperative hydrocephalus exacerbation were more likely to increase the occurrence of meningitis. In contrast, preoperative severe hydrocephalus requiring EVD led to increased rates of postoperative complications. CONCLUSIONS: For pediatric patients with intracranial tumors who need to undergo resection through a suboccipital midline approach, dural repair using the nuchal ligament is safe, cost-effective, and time saving and significantly reduces postoperative complications.

MYC/NBS1-Mediated DNA Damage Response is Involved in the Inhibitory Effect of Hydroxysafflor Yellow A on Glioma Cells.

BACKGROUND: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells. METHODS: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. After treating the cells with HSYA, silenced MYC, or overexpressed NBS1, the viability, apoptosis, proliferation, invasion, migration, and DNA damage of the glioma cells were detected by MTT, flow cytometry, colony formation, transwell, wound healing, and γH2AX immunofluorescence assays, respectively. IC50 of HSYA in glioma cells was analyzed by Probit regression analysis. The expressions of MYC, NBS1, factors related to migration, invasion, apoptosis, and DNA damage of the glioma cells were determined by Western blot or RT-qPCR. RESULTS: MYC and NBS1 were high-expressed in glioma, and NBS1 was targeted by MYC. HSYA and siRNA targeting MYC inhibited the cell viability, proliferation, invasion, migration, and induced the cell apoptosis of glioma cells. HSYA upregulated the expressions of MYC, γH2AX, E-Cadherin, Bax, and Cleaved-PARP1, stimulated the activation of NBS1, MRE11, RAD50, and ATM, and downregulated the expressions of N-Cadherin and Bcl2 in glioma cells. SiMYC decreased the IC50 of HSYA in the glioma cells, enhanced the sensitivity of glioma cells to HSYA, and inhibited the activation of NBS1 and ATM. NBS1 overexpression reversed the effect of siRNA targeting MYC on glioma cells. CONCLUSION: MYC silencing inhibited the DNA damage response via regulation of NBS1, leading to DNA repair deficiency, and subsequently enhanced the sensitivity of glioma cells to HSYA.

Classification of Peritumoral Veins in Convexity and Parasagittal Meningiomas and Its Significance in Preventing Cerebral Venous Infarction.

OBJECTIVE: The medium (2-4 cm) convexity located closer to the sinus and parasagittal meningiomas (Sindou type I-Ⅲ) without obvious invasion of the superior sagittal sinus are considered simple to operate on. However, the tumors are often accompanied by the cortical bridging vein. Because of lack of collateral vein circulation in cortical areas, the damage of peritumoral veins will subsequently lead to venous infarction. To avoid the serious complications caused by intraoperative injury of peritumoral veins, it is necessary to define the classification of the progression of peritumoral veins and tumors to guide surgical safety. METHODS: The clinical information of 57 patients with convexity and parasagittal meningiomas was collected and retrospectively analyzed. All patients underwent preoperative magnetic resonance imaging and magnetic resonance venography scanning to observe the imaging characteristics of peritumoral veins and preoperative evaluation. The actual relationship between the tumor and peritumoral vein was observed intraoperatively. Postoperative computed tomography and magnetic resonance imaging were used to determine tumor resection and the presence of venous infarction. RESULTS: According to preoperative magnetic resonance venography and intraoperative findings, we divided the peritumoral veins into 3 types: type A (n = 33, 57.9%), the vein surrounds the tumor; type B (n = 15, 26.3%), the vein is located on the ventral side of the tumor; and type C (n = 9, 15.8%), the vein is located on the dorsal side of the tumor. Peritumoral vein injury occurred in 6 cases followed by serious complications. Treatments were as follows: 4 cases underwent decompression and 2 cases were treated conservatively. The prognosis Glasgow Outcome Scale (GOS) scores were as follows: 3 cases were score 5 for injury of posterior frontal vein or middle frontal vein, 2 cases were score 3 for injury of the central vein, 1 case was score 1 for death due to injury of the central vein. All cases were followed up for 6 months. CONCLUSIONS: Attention should be paid to the peritumoral vein of special meningiomas. Injured vein in the medial third of superior sagittal sinus carries a high rate of postoperative morbidity. Understanding the type of peritumoral veins preoperatively can be used as a guide in determining the corresponding protective strategy during surgery, which can significantly decrease postoperative disability and improve quality of life.

Treatment of Relapsed Chronic Subdural Hematoma in Four Young Children with Atorvastatin and Low-dose Dexamethasone.

Chronic subdural hematoma (CSDH) can develop in children in rare cases. Burr-hole drainage (BHD) is the treatment of choice, but it is associated with a high rate of recurrence. This report describes four cases of pediatric patients (1-7 yrs of age) with post-BHD relapsed CSDH who were successfully treated with a drug regimen that included 2.5-5 mg atorvastatin daily combined with dexamethasone with stepwise-decreasing dosing for a total of 4 weeks. After 4 weeks of treatment, the hematoma was completely resolved in three patients and significantly reduced in one patient. During the treatment, no patient reported clinically significant adverse events. No patient experienced hematoma relapse during the follow-up period that lasted for up to 4 years. This case report suggests the need for a randomized placebo-controlled trial to evaluate this drug regimen for nonsurgical treatment of patients with relapsed CSDH.

Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats.

Chronic subdural hematoma (CSDH) is a neurological disorder with a substantial recurrence rate. Atorvastatin is an effective drug for treating hyperlipidemia and known to improve neurological outcome after intracerebral hemorrhage. Previous studies have reported that atorvastatin treatment promotes hematoma absorption in CSDH, while the underlying mechanisms remain unclear. In this study, we investigated whether the anti-inflammatory effects of atorvastatin mediate absorption of CSDH. 144 male, Wistar rats (6 months old) were randomly divided into the following groups: 1) sham surgery control, 2) treatment: CSDH + atorvastatin, and 3) vehicle control: CSDH + saline. Atorvastatin or saline was orally administered daily for 19 days after CSDH procedure. A T2WI MRI was used to evaluate CSDH volume changes during the time course of the study. Flow cytometry and immunohistochemical staining were used to measure the number of regulatory T cells (Treg). ELISA was used to measure cytokine level in the hematoma border. Neurological function and cognitive outcome were evaluated using Foot-Fault test and Morris Water Maze test, respectively. When compared to saline treatment, atorvastatin treatment accelerated the absorption of CSDH as indicated by decreased hematoma volume in T2WI MRI data on 14th and 21st day after CSDH (P<0.05). Atorvastatin treatment significantly increased the number of Treg in circulation and hematoma border from 3rd to 21st day after CSDH. Atorvastatin treatment significantly decreased the levels of interleukins (IL-6 and IL-8) and tumor necrosis factor-α (TNF-α), but increased IL-10 level in the hematoma border. Atorvastatin treatment also improved neurological function and cognitive outcome compared to vehicle treated group. Atorvastatin induced anti-inflammatory responses and increased Treg in circulation and brain which may contribute to the accelerated CSDH absorption in rats.

Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist.

OBJECTIVES: Progesterone (P4) has the potential therapeutic effects for traumatic brain injury (TBI) whose recovery depended on the enhanced angiogenesis. Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We previously demonstrated that P4 administration improved circulating EPC level and neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented angiogenic potential of EPC and the angiogenesis-related neurorestoration after TBI through classical progesterone receptor (PR). MATERIALS AND METHODS: EPC derived from rats were stimulated with graded concentrations (0, 10-10 , 10-9 , 5 × 10-9 , 10-8 , 10-7  mol/L) of P4 or 10-6  mol/L ulipristal acetate (UPA, a PR antagonist). Male rats were subjected to cortical impact injury and treated with (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. RESULTS: It showed that P4 improved the angiogenic potential of EPC, including tube formation, adhesion, migration and vascular endothelial growth factor secretion, in a dose-dependent fashion with the maximal effect achieved at 10-9  mol/L P4. High concentration (10-7  mol/L) of P4 impaired the angiogenic potential of EPC. Notably, 10-6  mol/L UPA antagonized the stimulatory effects of 10-9  mol/L P4. After administrating P4, a significant improvement of neurological function and the restoration of the leaked blood-brain barrier were observed as well as a reduction of the brain water content. Both vessel density and expression of occludin of vessels were increased. When UPA was administered with P4, the neural restoration and angiogenesis were all reversed. Western blot showed that 10-9  mol/L P4 increased the content of PRA and PRB of EPC, while 10-7  mol/L P4 reduced the content of both PR isoforms, but there was no change found in the TBI rats. CONCLUSIONS: It may suggest that P4-mediated angiogenic activity of EPC and angiogenesis in TBI rats were antagonized by PR antagonist.

Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway.

OBJECTIVES: Progesterone treatment can effectively increase levels of circulating endothelial progenitor cells (EPCs) and improve neurological functional outcome in a traumatic brain injury (TBI) rat model. However, the mechanisms of progesterone's effects on EPC viability remain elusive. The CXCL12/CXCR4 (CXC chemokine ligand 12/CXC chemokine receptor 4) signalling pathway regulates cell proliferation; we hypothesize that it mediates progesterone-induced EPC viability. MATERIALS AND METHODS: EPCs were isolated from bone marrow-derived mononuclear cells (BM-MNCs) and treated with progesterone (5, 10 and 100 nm). MTS assay was used to investigate EPC viability. Protein expression was examined by Western blotting, ELISA assay and flow cytometry. Cell membrane and cytoplasm proteins were extracted with membrane and cytoplasm protein extraction kits. CXCR4 antagonist (AMD3100) and phosphatidylinositol 3-kinases (PI3K) antagonist (LY294002) were used to characterize underlying mechanisms. RESULTS: Progesterone-induced EPC viability was time- and dose-dependent. Administration of progesterone facilitated EPC viability and increased expression of CXCL12 and phosphorylated Akt (also known as protein kinase B, pAkt) activity (P < 0.05). Progesterone did not regulate CXCR4 protein expression in cultured EPC membranes or cytoplasm. However, progesterone-induced EPC viability was significantly attenuated by AMD3100 or LY294002. Inhibition of the signalling pathway with AMD3100 and LY294002 subsequently reduced progesterone-induced CXCL12/CXCR4/PI3K/pAkt signalling activity. CONCLUSIONS: The CXCL12/CXCR4/PI3K/pAkt signalling pathway increased progesterone-induced EPC viability.

A rat model of chronic subdural hematoma: Insight into mechanisms of revascularization and inflammation.

Chronic subdural hematoma (CSDH) is a common neurological occurrence in the elderly population with significant impact on the quality of life and work. Studies have attempted to determine the risk factors and pathophysiological mechanisms of CSDH using models in numerous mammalian species. To date, these animal models have only been able to reproduce limited durations of hematoma which does not accurately reflect the chronic state of CSDH. To address some of these challenges we modified a rat model of CSDH using two consecutive injections of autologous blood resulting in a hematoma of more than three weeks. We observed inflammatory and angiogenic changes related to the development and recovery of CSDH. In this study the technique for producing a CSDH in a small animal model had a success rate of 78.13%. The hematoma was sustainable up to 24 days. Hematoma resolution was associated with a gradual decrease in local pro-inflammatory factors and gradual increase in anti-inflammatory factors as well as proliferation and subsequent maturation of newly formed vessels. These events were also associated with improved behavioral outcome. Expression of anti-inflammatory cytokines also paralleled reabsorption of the hematoma. Reduction in hematoma size was also associated with neurological recovery. These data suggest that vessel maturation and anti-inflammatory pathways may contribute to the resolution of CSDH and neurological recovery. The regulation of the two mechanisms is a potential target for the treatment of CSDH. The modified model of rat CSDH demonstrated a high level of reproducibility in our hands and may be useful in future CSDH studies.