Prediction of blood supply in vestibular schwannomas using radiomics machine learning classifiers.

This study attempts to explore the radiomics-based features of multi-parametric magnetic resonance imaging (MRI) and construct a machine-learning model to predict the blood supply in vestibular schwannoma preoperatively. By retrospectively collecting the preoperative MRI data of patients with vestibular schwannoma, patients were divided into poor and rich blood supply groups according to the intraoperative recording. Patients were divided into training and test cohorts (2:1), randomly. Stable features were retained by intra-group correlation coefficients (ICCs). Four feature selection methods and four classification methods were evaluated to construct favorable radiomics classifiers. The mean area under the curve (AUC) obtained in the test set for different combinations of feature selecting methods and classifiers was calculated separately to compare the performance of the models. Obtain and compare the best combination results with the performance of differentiation through visual observation in clinical diagnosis. 191 patients were included in this study. 3918 stable features were extracted from each patient. Least absolute shrinkage and selection operator (LASSO) and logistic regression model was selected as the optimal combinations after comparing the AUC calculated by models, which predicted the blood supply of vestibular schwannoma by K-Fold cross-validation method with a mean AUC = 0.88 and F1-score = 0.83. Radiomics machine-learning classifiers can accurately predict the blood supply of vestibular schwannoma by preoperative MRI data.

Prognostic Predictors of Early Outcomes and Discharge Status of Patients Undergoing Decompressive Craniectomy After Severe Traumatic Brain Injury.

OBJECTIVE: Although several prognostic factors for traumatic brain injury (TBI) have been evaluated, a useful predictive scoring model for the outcomes has not been developed for patients with severe TBI who undergo decompressive craniectomy (DC). The aim of the present study was to determine independent predictors and develop a multivariate logistic regression equation to predict the early outcome and discharge status for patients with severe TBI who have undergone DC. METHODS: A total of 13 different variables were evaluated. The data from all 278 patients with severe TBI who had undergone DC in the present study were retrospectively evaluated from July 2011 to June 2017. Using univariate, multiple logistic regression and prognostic regression scoring equations it was possible to draw receiver operating characteristic curves to predict the early outcomes and discharge status after TBI. RESULTS: We found that younger age (P = 0.012), no significant medical history (P = 0.044), diameter of both pupils <4 mm (P = 0.032), higher admission Glasgow coma scale score (P = 0.004), no tracheotomy (P < 0.001), and DC for severe TBI were associated with a favorable early outcome and discharge status. Using receiver operating characteristic curves to predict the probability of a favorable outcome, the sensitivity was 80.0% and the specificity was 79.5%. CONCLUSIONS: Our preliminary findings have shown that 5 variables can be used as independent predictors in assessing the early outcome and discharge status for patients with severe TBI after DC.

Tanycytic ependymoma of filum terminale: Clinical characteristics and surgical outcomes.

Tanycytic ependymoma (TE), a rare subtype of ependymoma, was classified as grade II ependymoma by the World Health Organization in 2000 and 2007. Preoperative diagnosis of TE is challenging due to its similarities to schwannoma and astrocytoma; therefore, differentiation is required. The present study investigated the clinical, imaging and pathological characteristics of TE in the filum terminale. A retrospective analysis was conducted on the clinical, imaging, pathological and immunohistochemical characteristics of 8 patients with TE in the filum terminale and the relevant literature was reviewed. Of the 8 patients 7 were female and 1 was male, with an age range of 24-62 years old. The primary clinical symptom observed was lumbago, accompanied by lower limb pain and numbness. Magnetic resonance imaging predominantly identified isointensity on thoracic (T) 1-weighted images and iso- or hyperintense signal intensity on T2-weighted images, with homogeneous or inhomogeneous enhancement. All patients underwent resection of the tumor through a posterior median approach, and total resection was acighieved in 7 patients. During postoperative follow-up, all patients experienced improvement compared with their preoperative status, and were without tumor recurrence. The present study comprised the largest group of cases with TE in the filum terminale reported so far, to the best of our knowledge, which could foster a better understanding of this disease. Complete surgical resection of the tumor has the greatest effectiveness of any treatment for TE in the filum terminale. Postoperative histological examination, immunohistochemistry and electron microscopy for tumor specimens may assist in its diagnosis and differential diagnosis.

Decompressive craniectomy protects against hippocampal edema and behavioral deficits at an early stage of a moderately controlled cortical impact brain injury model in adult male rats.

A decompressive craniectomy (DC) has been shown to be a life-saving therapeutic treatment for traumatic brain injury (TBI) patients, which also might result in post-operative behavioral dysfunction. However, there is still no definite conclusion about whether the behavioral dysfunction already existed at an early stage after the DC operation or is just a long-term post-operation complication. Therefore, the aim of the present study was to analyze whether DC treatment was beneficial to behavioral function at an early stage post TBI. In this study, we established a controlled cortical impact injury rat model to evaluate the therapeutic effect of DC treatment on behavioral deficits at 1 d, 2 d, 3 d and 7 d after TBI. Our results showed that rats suffered significant behavioral and mood deficits after TBI compared to the control group, while decompressive craniectomy treatment could normalize MMP-9 expression levels and reduce hippocampal edema formation, stabilize the expression of Synapsin I, which was a potential indicator of maintaining the hippocampal synaptic function, thus counteracting behavioral but not mood decay in rats subjected to TBI. In conclusion, decompressive craniectomy, excepting for its life-saving effect, could also play a potential beneficial neuroprotective role on behavioral but not mood deficits at an early stage of moderate traumatic brain injury in rats.

Clinical Features, Treatment, and Prognostic Factors of 56 Intracranial and Intraspinal Clear Cell Meningiomas.

OBJECTIVE: Intracranial and intraspinal clear cell meningiomas (CCMs) are rarely reported because of their extremely low incidence, and the current understanding of CCM is poor. The purpose of this study was to analyze the incidence and the clinical, radiologic, pathologic, and prognostic features of intracranial and intraspinal CCMs. METHODS: Among 14,310 cases of intracranial and intraspinal meningiomas that were surgically treated between 2006 and 2016 at Beijing Tian Tan Hospital, 56 were chosen for analysis and retrospectively reviewed. To determine which parameters were associated with longer progression-free survival (PFS) and overall survival (OS), statistical analysis was performed. RESULTS: CCMs accounted for approximately 0.39% of all intracranial and intraspinal meningiomas. Patients with CCM had a mean age of 32.3 years and there was a female predilection (20 males and 36 females). Gross total resection was achieved in 35 cases, and subtotal resection was achieved in 21 cases. All patients were followed up for 10-206 months after surgery. Twenty-six patients experienced tumor recurrence, and the median PFS was 48.0 months. The 1-year, 3-year, and 5-year PFS was 87.5%, 59.8%, and 41.8%, respectively. Twelve patients died of tumor recurrence, and the median OS was not available. The 1-year, 3-year, and 5-year OS was 98.2%, 91.3%, and 65.8%, respectively. Univariate analysis showed that total tumor removal was significantly associated with a better prognosis. Multivariate analysis confirmed only Simpson grade III and IV resection as an independent risk factor for shorter PFS. Radiotherapy mildly improved PFS after both gross total resection and subtotal resection, showing no significant difference because of the small sample size and short follow-up duration. CONCLUSIONS: CCM is a rare subtype of World Health Organization grade II meningioma. CCM typically involves young patients and shows a female predilection and high recurrence rate. When possible, total resection is the primary and most suitable treatment for CCM. For patients with primary tumors, radiotherapy is recommended after the initial operation regardless of the extent of resection. For patients with disease recurrence, secondary surgery combined with radiotherapy might serve as an effective treatment.

Clinical features, surgical management, and prognostic factors of secretory meningiomas: a single-center case series of 149 patients.

Secretory meningioma (SM) is a rare histological subtype of the meningioma family. Few reports investigating SM have been published due to its extremely low incidence; thus, the current understanding of this disease is poor. We analyzed the incidence and clinical, radiological, pathological, and prognostic features of SM. Approximately 12,380 intracranial meningiomas were surgically resected at Beijing Tiantan Hospital between April 2008 and January 2017. All pathologically confirmed SM cases were identified. SMs accounted for approximately 1.2% of the intracranial meningiomas (149 of 12,380). The patients with SM had a mean age of 51.0 years and were predominantly female (112 female and 37 male). Radiologically, peritumoral brain edema was observed in 49 (32.9%) patients. Gross total resection was achieved in 115 (77.2%) cases. At the 35-months median follow-up (range 4-109 months), six patients had tumor recurrence, and one patient died from the tumor recurrence. The 5-year progression-free survival rates were 95.9%, and the 5-year overall survival rate was 99.3%. A skull base location and a tumor size ≥ 3.5 cm were significantly associated with poor short-term outcomes, and a skull base location was significantly associated with an increased risk of poor long-term outcomes (P < 0.05). A skull base location (OR 3.797; 95% CI 1.071-13.468; P = 0.039) and tumor size ≥ 3.5 cm (OR 2.616; 95% CI 1.107-6.181; P = 0.028) were independent risk factors for non-gross total resection. A son-skull base location (OR 0.070; 95% CI 0.028-0.177; P = 0.001) was the only independent risk factor that correlated with more severe peritumoral brain edema. SM is a rare subtype of meningiomas with a female predominance and low recurrence. Our results highlight the risk factors for short- and long-term outcomes, which can be useful for selecting treatments and predicting prognosis. Microsurgical treatment of a skull base SM remains a formidable challenge due to a large tumor size and critical neurovascular structure encasement.

Brain metastatic alveolar soft-part sarcoma: Clinicopathological profiles, management and outcomes.

Alveolar soft-part sarcoma (ASPS) is a rare sarcoma that presents in the buttocks or thigh of young adults and often metastasizes to the brain. The present study examined the clinical features and morphology of brain metastatic ASPS. The case records of eight patients with brain metastatic ASPS admitted between November 2008 and March 2015 were reviewed. The relevant clinical data (including patient age and sex, neuroimaging studies, histopathological and immunohistochemical features, surgical records and follow-up reports) were collected through a review of patient records. The sex distribution was 3:1 male to female and the age ranged between 15 and 33 years at the time of surgery. In total, five patients with brain metastases had concurrent pulmonary metastases. The lesions were hypointense on T1-weighted images in every patient, hyperintense on T2-weighted images in six patients and contrast enhancement was present in all patients. The most notable immunohistochemical feature was strong immunohistochemical staining for TFE3 in each patient. Gross total resection was performed in all eight patients, with two patients undergoing adjuvant radiotherapy and one undergoing adjuvant chemotherapy. Four recurrent cases were observed during the follow-up. TFE3 staining and knowledge of its microscopic characteristics would facilitate earlier diagnosis: Early diagnosis with a multidisciplinary, multimodal approach to treatment is required to achieve extended disease-free survival in patients with brain metastatic ASPS.

A Tortuous Process of Surgical Treatment for a Large Calcified Chronic Subdural Hematoma.

BACKGROUND: Calcified chronic subdural hematoma (CCSDH) is a rare disease for which no standard approach to treatment has been established. Reports covering both burr hole trepanation and craniotomy for CCSDH are rare. Furthermore, infection of CCSDH after the burr hole trepanation has not been reported in the literature. CASE DESCRIPTION: A 61-year-old man presented with left frontotemporoparietal CCSDH demonstrated on computed tomography (CT) scan. The patient underwent 2 separate burr hole trepanations with intraoperative irrigation and postoperative drainage. These procedures led to infection of the CCSDH. The patient eventually underwent an open craniotomy to provide complete removal of the hematoma. CONCLUSIONS: Owing to the complex contents of a CCSDH, burr hole trepanation cannot adequately drain the hematoma or relieve the mass effect. Craniotomy is a much more reliable approach for achieving complete resection of a CCSDH.

Clinical, Radiologic, and Pathologic Features of 56 Cases of Intracranial Lymphoplasmacyte-Rich Meningioma.

OBJECTIVE: Intracranial lymphoplasmacyte-rich meningioma (LPRM) is rarely reported because of its extremely low incidence, and current understanding of this disease is poor. We analyzed the incidence and clinical, radiologic, pathologic, and prognostic features of intracranial LPRMs. METHODS: Approximately 10,908 intracranial meningiomas were surgically resected in Beijing Tiantan Hospital between June 2009 and November 2016. All pathologically proven LPRM cases were identified. Statistical analysis was performed to determine which parameters were associated with prognoses and tumor resection. RESULTS: LPRMs accounted for approximately 0.51% of intracranial meningiomas (56 of 10,908). Patients with LPRM had a mean age of 44.6 years and there was no significant gender preference (28 male and 28 female). Gross total resection was achieved in 45 cases, subtotal resection in 9 cases, and partial resection in 2 cases. At discharge, Karnofsky Performance Scale scores and neurologic function improved in 42 cases (75.0%) and worsened in 14 cases (25.0%). At the 41.5 months median follow-up (range, 5-97 months), 5 patients had tumor recurrence, and the 3-year and 5-year progression-free survival rates were 94.6% and 92.9%, respectively. One patient died of tumor recurrence. At the latest follow-up, Karnofsky Performance Scale scores improved in 48 cases (85.7%), worsened in 7 cases (12.5%), and 1 patient died (1.8%). Univariate analysis showed that the extent of tumor resection and tumors located in the skull base were significantly associated with short-term outcomes. Skull base location was significantly associated with increased risk of worse long-term outcomes. Tumor size ≥45 mm, poorly defined tumor border, and skull base location significantly limited the extent of tumor resection. CONCLUSIONS: Intracranial LPRM is a rare subtype of meningioma with no gender difference and low recurrence. Long-term survival is expected, although tumors located in the skull base and bone destruction are independent risk factors of poor long-term outcomes. Microsurgical treatment of skull base LPRM remains a formidable challenge because of poorly defined borders and critical neurovascular structure encasement. Radical tumor resection, which induces severe neurologic deficits, is unnecessary.

The clinical features and surgical outcomes of intracranial tanycytic ependymomas: a single-institutional experience.

Tanycytic ependymoma is a rare subtybe of ependymoma with a predilection for the spinal cord and intracranial tanycytic ependymoma is thus extremely rare. Most studies on intracranial tanycytic ependymomas included only one or two cases. Here we report nine patients with pathologically confirmed intracranial tanycytic ependymomas. The clinical characteristics, including radiological and histological examination, operative records, and prognoses were reviewed. The case series included six male and three female patients with an average age of 19.3 years. Tumors were located in the lateral ventricle (3/9), the fourth ventricle (2/9), and the supratentorial extraventricle (4/9). Gross total resection (GTR) of the tumor was achieves in seven cases, and subtotal resection (STR) was achieved in the other two cases. One patient died 21 months after discharge. The left eight patients showed improved symptoms after surgery, and no tumor recurrence was found in these cases during the follow-up. It seems that intracranial tanycytic ependymoma has the best long-term prognosis compared to the other two subtypes of ependymoma. According to our experience, we recommend surgery including GTR and STR followed by radiotherapy for patients with intracranial tanycytic ependymomas.

The Clinical Features and Surgical Outcomes of Spinal Cord Tanycytic Ependymomas: A Report of 40 Cases.

OBJECTIVE: Spinal cord tanycytic ependymomas (TEs) rarely are reported because of extremely low incidence. Understanding of this disease is therefore poor. The aim of this study was to analyze the incidence and clinical, radiologic, pathologic, and prognostic features of spinal cord TEs. METHODS: Approximately 4000 spinal cord tumors were resected surgically in Beijing Tiantan Hospital between April 2009 and May 2016. We identified all cases of pathologically proved TEs among these patients. RESULTS: TEs accounted for approximately 1% of spinal cord tumors (40 of an estimated 4000). Patients with TE were a mean age of 40.0 years and had no significant sex preference (21 male and 19 female). The median diameter of the maximal tumor was 54.2 mm (range, 16-153 mm). The mean preoperative Japanese Orthopedic Association (JOA) score was 13.0. Radiologically, 47.5% (19/40) cases showed poorly defined tumor border, and 40% (16/40) of them showed preoperative syringomyelia. Gross total resection was achieved in 30 cases, subtotal resection in 8, and partial resection in 2. At the time of discharge, JOA score and neurologic function showed improvement in 26 cases (65%), no change in 12 cases (30%), and worsening in 2 cases (5%). At a median follow-up of 43 months (range, 7-101 months), 1- and 5-year progression-free survival rates were 100.0% and 97.5%, respectively. Only one patient had tumor recurrence which was found 30 months after surgery. No patient died of tumor recurrence. At the latest follow-up, JOA score showed improvement in 30 cases (75%), no change in 8 cases (20%), and worsening in 2 cases (5%). Univariate analysis revealed that tumor size and preoperative JOA score were significantly associated with the short-term outcomes. Meanwhile, age ≥40 years, tumor size ≥50 mm, non-gross total resection, and preoperative JOA score <14 were significantly associated with an increased risk of worsened long-term outcomes. Poorly defined tumor border and preoperative JOA score <14 significantly limited the extent of tumor resection. CONCLUSIONS: Spinal cord TE is a rare subtype of ependymomas with low recurrence. Long-term survival can be expected, although poorly defined tumor border is an independent predictor of long-term outcomes. Microsurgical treatment of spinal cord TEs remains a formidable challenge due to the poorly defined border and critical neurovascular structures encasement. It is unnecessary for radical tumor resection at the cost of severe neurologic deficits.

Protective Functions of PJ34, a Poly(ADP-ribose) Polymerase Inhibitor, Are Related to Down-Regulation of Calpain and Nuclear Factor-κB in a Mouse Model of Traumatic Brain Injury.

OBJECTIVES: Poly(ADP-ribose) polymerase (PARP), calpain, and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathologic conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participates in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). METHODS: PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI. We then performed a histopathologic analysis, and we measured calpain activity and protein levels in all animals. The cytosolic, mitochondria, and nuclear fractions were prepared and used to determine the levels of PARP, calpastatin, NF-κB p65, inhibitory-κB-α, tumor necrosis factor-α, interleukin-1ß, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2. We then measured blood-brain barrier disruption using electron microscopy at 6 and 24 hours after CCI. RESULTS: Treatment with PJ34 markedly reduced the extent of both cerebral contusion and edema, improved neurologic scores, and attenuated blood-brain barrier damage resulting from CCI. Our data showed that the cytosolic and nuclear fractions of calpain and NF-κB were up-regulated in the injured cortex and that these changes were reversed by PJ34. Moreover, PJ34 significantly enhanced the calpastatin and inhibitory-κB levels and decreased the levels of inflammatory mediators. CONCLUSIONS: PARP inhibition by PJ34 suppresses the overactivation of calpain and the production of inflammatory factors that are caused by NF-κB activation and attenuates neuronal cell death in a mouse model of CCI.

Portable near-infrared rapid detection of intracranial hemorrhage in Chinese population.

BACKGROUND: Secondary brain injury is the main cause of mortality from traumatic brain injury (TBI). One hallmark of TBI is intracranial hemorrhage, which occurs in 40-50% of severe TBI cases. Early identification of intracranial hematomas in TBI patients allows early surgical evacuation, and can reduce the case-fatality rate of TBI. Since pre-hospital care is the weakest part of Chinese emergency care, there is an urgent need for a capability to detect brain hematomas early. The purpose of this observational study was to evaluate the performance of a near infrared (NIR) based, device to screen for traumatic intracranial hematomas in Chinese population. METHODS: Data was collected using the NIR device at the time of a computed tomography (CT) or magnetic resonance imaging (MRI) scan was performed to evaluate a suspected TBI. 85 patients were included in the per protocol population. Of the 85 patients, 45 were determined by CT scan to have intracranial hemorrhage. The CT and MRI scans were read by an independent neuroradiologist who was blinded to the NIR measurements. RESULTS: The NIR device demonstrated sensitivity of 95.6% (95% confidence intervals [CI] 83.6-99.2%) and specificity of 92.5% (CI 78.5-98%) in detecting intracranial hematomas larger than 3.5ml in volume, and that were less than 2.5cm from the surface of the brain. CONCLUSION: These results confirm in Chinese population the results of previous studies that demonstrated a NIR based device can reliably screen for intracranial hematomas that are likely to be of clinical importance.

Protective Effects of Calpain Inhibition on Neurovascular Unit Injury through Downregulating Nuclear Factor-κB-related Inflammation during Traumatic Brain Injury in Mice.

BACKGROUND: In addition to neurons, all components of the neurovascular unit (NVU), such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury (TBI). Previous studies have shown that excessive stimulation of calpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact (CCI). METHODS: One hundred and eight mice were divided into three groups: the sham group, the control group, and the MDL28170 group. MDL28170 (20 mg/kg), an efficient calpain inhibitor, was administered intraperitoneally at 5 min, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier (BBB) disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. RESULTS: The MDL28170 treatment significantly reduced the extent of both cerebral contusion (MDL28170 vs. vehicle group, 16.90 ± 1.01 mm΃ and 17.20 ± 1.17 mm΃ vs. 9.30 ± 1.05 mm΃ and 9.90 ± 1.17 mm΃, both P < 0.001) and edema (MDL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P < 0.05), improved neurological scores (MDL28170 vs. vehicle group, 7.50 ± 0.45 and 6.33 ± 0.38 vs. 12.33 ± 0.48 and 11.67 ± 0.48, both P < 0.001), and attenuated NVU damage resulting (including tight junction (TJ), basement membrane, BBB, and neuron) from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation (tumor necrosis factor-α [TNF-α]: MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62 ± 0.08 vs. 1.59 ± 0.10 and 2.18 ± 0.10, both P < 0.001; inducible nitric oxide synthase: MDL28170 vs. vehicle group, 4.51 ± 0.23 vs. 6.23 ± 0.12, P < 0.001 at 24 h; intracellular adhesion molecule-1: MDL28170 vs. vehicle group, 1.45 ± 0.13 vs. 1.70 ± 0.12, P < 0.01 at 24 h) and lessened both myeloperoxidase activity (MDL28170 vs. vehicle group, 0.016 ± 0.001 and 0.016 ± 0.001 vs. 0.024 ± 0.001 and 0.023 ± 0.001, P < 0.001 and 0.01, respectively) and matrix metalloproteinase-9 (MMP-9) levels (MDL28170 vs. vehicle group, 0.87 ± 0.13 and 1.10 ± 0.10 vs. 1.17 ± 0.13 and 1.25 ± 0.12, P < 0.001 and 0.05, respectively) at 6 h and 24 h after CCI. CONCLUSIONS: These findings demonstrate that MDL28170 can protect the structure of the NVU by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and supporting the integrity of TJ during acute TBI.

Saikosaponin a protects TBI rats after controlled cortical impact and the underlying mechanism.

The inflammatory response plays a significant role in neuronal cell death and functional deficits after Traumatic brain injury (TBI). Importantly, anti-inflammatory agents have neuroprotective effects. To date, however, no studies have investigated the neuroprotective effects of Saikosaponin a (SSa) after TBI. In the present study, rats with controlled cortical impact (CCI) were used to investigate the neuroprotective effects of SSa. The results showed that SSa reduced body weight loss, improved neurological functions andcognition, and reduced brain edema and blood brain barrier permeability after CCI. Moreover, SSa inhibited aquaporin-4 (AQP-4), matrix metalloprotein-9 (MMP-9), mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (c-JNK), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The reduction in the loss of occludin mediated by SSa may partially account for its neuroprotective effects. Together, our results suggest that SSa appears to counteract the inflammatory response and neurological function deficits after TBI and possibly via an anti-inflammatory response and inhibition of the MAPK signaling pathway.

Protective effects of PARP inhibitor, PJ34, is related to down-regulation of calpain and NF-κB in a mouse model of TBI.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). MATERIALS AND METHODS: PJ34 (10 mg kg-1), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI. A neurobehavioural evaluation and a histopathological analysis were then performed and the contusion volume, calpain activity and protein levels were measured in all animals. RESULTS: Treatment with PJ34 markedly reduced neurological deficits, decreased contusion volume and attenuated necrotic and apoptotic neuronal cell death 24 hours after CCI. The data showed that the cytosolic and nuclear fractions of calpain and NF-κB were up-regulated in the injured cortex and that these changes were reversed by PJ34. Moreover, PJ34 significantly enhanced the calpastatin and IκB levels and decreased the levels of inflammatory mediators. CONCLUSIONS: PARP inhibition by PJ34 suppresses the over-activation of calpain and the production of inflammatory factors that are caused by NF-κB activation and it improves neurological functioning, decreases the contusion volume and attenuates neuronal cell death in a mouse model of CCI.

Primary Intracranial Alveolar Soft-Part Sarcoma: Report of Two Cases and a Review of the Literature.

BACKGROUND: Alveolar soft part sarcoma (ASPS), a rare malignant soft-tissue sarcoma affecting mainly adolescents and young children, frequently metastasizes to the brain. Primary intracranial ASPS, however, is extremely rare. We present 2 cases of primary intracranial ASPS without demonstrable systemic lesions. CASE PRESENTATION: We report 2 cases of primary intracranial lesions that were surgically treated, and a postoperative diagnosis of ASPS was determined in both of the cases. The tumor in the 28-year-old female patient completely resolved after a treatment course consisting of surgical intervention and radiotherapy. After a follow-up period of 27 months, the patient was tumor-free. The other patient was a 13-year-old boy with a right middle cranial fossa tumor who experienced subtotal surgery, experienced a tumor relapse, and died 2 years after surgery. CONCLUSIONS: This is the fifth report about primary intracranial ASPS. We herein present the clinical pathologic characteristics, imaging features, and differential diagnosis of primary ASPS of the brain. Gross total resection is the most effective therapeutic option for primary intracranial ASPS.

Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats.

Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.