Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats.

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 105 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries.

[VEGF enhances reconstruction of neurovascular units in the brain after injury].

Vascular endothelial growth factor (VEGF) was originally recognized as a substance predominantly with vascular permeability and angiogenesis. Recently, more and more evidence indicated that VEGF is expressed in the neurons of the developing and adult brains. Functional investigation demonstrated that VEGF shows several important effects on the neuronal development and physiological function. For example, VEGF accelerates the development of neurons and neural dendritic and axon growth. Besides, VEGF directly and acutely regulates the functions of multiple ion channels of the neuron membrane and changes neural excitability. In traumatic or ischemic injured brains, VEGF produces neuroprotection, enhances capacity of adult neurogenesis and transformation of astroglial cells into new neurons, which are fundamental basis for re-establishment of neural network. Based on the knowledge obtained from the literatures, we propose that VEGF may play very important roles in neural plasticity in the normal brain, and the reconstruction of neurovascular units and neural repair in the traumatic injured brain. This review mainly focuses on neural activity and repair roles of VEGF in adult mammalian brains. Further study on the mechanism of VEGF's neurobiological effects in the brain will be helpful for understanding the regulation of brain functions and developing new therapeutic strategy for prevention of neurodegeneration of the brain.

Pure endoscopic resection of pineal region tumors through supracerebellar infratentorial approach with 'head-up' park-bench position.

OBJECTIVE: Neuroendoscopic resection via supracerebellar infratentorial (SCIT) approach is adequate for some indicated pineal region tumors with the natural infratentorial corridor. We described this full endoscopic approach through a modified 'head-up' park-bench position to facilitate the procedure. METHODS: We reviewed the clinical and radiological data of four patients with pineal region lesions who underwent pure endoscopic tumor resection through the SCIT approach with this modified position. The related literature concerning fully endoscopic pineal region tumor resection was also reviewed. RESULTS: This cohort included four patients with pineal region tumors. External ventricular drainage (Ommaya reservoir) was performed in three patients with hydrocephalus in advance. The average tumor volume was 19.2 ± 17.2 cm3. Pathological examination confirmed two mixed germinomas, one glioblastoma multiforme, and one hemangioblastoma. Gross total resection (GTR) was achieved in all patients, and all patients recovered well without neurological deficits or surgical complications. Hydrocephalus was relieved among all patients. CONCLUSIONS: The pure endoscopic SCIT approach could enable safe and effective resection of pineal region tumors, even for relatively large lesions. The endoscope could provide a panoramic view and illumination of the deep-seated structures. Compared with the sitting position, this modified ergonomic position could be implemented easily.

Machine learning models predict coagulopathy in spontaneous intracerebral hemorrhage patients in ER.

AIMS: Coagulation abnormality is one of the primary concerns for patients with spontaneous intracerebral hemorrhage admitted to ER. Conventional laboratory indicators require hours for coagulopathy diagnosis, which brings difficulties for appropriate intervention within the optimal window. This study evaluates the possibility of building efficient coagulopathy prediction models using data mining and machine learning algorithms. METHODS: A retrospective cohort enrolled 1668 cases with acute spontaneous intracerebral hemorrhage from three medical centers, excluding those under antithrombotic therapies. Coagulopathy-related clinical parameters were initially screened by univariate analysis. Two machine learning algorithms, the random forest and the support vector machine, were deployed via an approach of four-fold cross-validation to screen out the most important parameters contributing to the occurrence of coagulopathy. Model discrimination was assessed using metrics, including accuracy, precision, recall, and F1 score. RESULTS: Albumin/globulin ratio, neutrophil count, lymphocyte percentage, aspartate transaminase, alanine transaminase, hemoglobin, platelet count, white blood cell count, neutrophil percentage, systolic and diastolic pressure were identified as major predictors to the occurrence of acute coagulopathy. Compared to support vector machine, the model based on the random forest algorithm showed better accuracy (93.1%, 95% confidence interval [CI]: 0.913-0.950), precision (92.4%, 95% CI: 0.897-0.951), F1 score (91.5%, 95% CI: 0.889-0.964), and recall score (93.6%, 95% CI: 0.909-0.964), and yielded higher area under the receiver operating characteristic curve (AU-ROC) (0.962, 95% CI: 0.942-0.982). CONCLUSION: The constructed models exhibit good prediction accuracy and efficiency. It might be used in clinical practice to facilitate target intervention for acute coagulopathy in patients with spontaneous intracerebral hemorrhage.

Virtual reality presurgical planning for cerebral gliomas adjacent to motor pathways in an integrated 3-D stereoscopic visualization of structural MRI and DTI tractography.

OBJECTIVE: Resection of gliomas invading primary motor cortex and subcortical motor pathway is difficult in both surgical decision-making and functional outcome prediction. In this study, magnetic resonance (MR) diffusion tensor imaging (DTI) data were used to perform tractography to visualize pyramidal tract (PT) along its whole length in a stereoscopic virtual reality (VR) environment. The potential value of its clinical application was evaluated. METHODS: Both three-dimensional (3-D) magnetic resonance imaging (MRI) and DTI datasets were obtained from 45 eligible patients with suspected cerebral gliomas and then transferred to the VR system (Dextroscope; Volume Interactions Pte. Ltd., Singapore). The cortex and tumor were segmented and reconstructed via MRI, respectively, while the tractographic PTs were reconstructed via DTI. All those were presented in a stereoscopic 3-D display synchronously, for the purpose of patient-specific presurgical planning and surgical simulation in each case. The relationship between increasing amplitude of the number of effective fibers of PT (EPT) at affected sides and the patients' Karnofsky Performance Scale (KPS) at 6 months was addressed out. RESULTS: In VR presurgical planning for gliomas, surgery was aided by stereoscopic 3-D visualizing the relative position of the PTs and a tumor. There was no significant difference between pre- and postsurgical EPT in this population. A positive relationship was proved between EPT increasing amplitude and 6-month KPS. CONCLUSIONS: 3-D stereoscopic visualization of tractography in this VR environment enhances the operators to well understand the anatomic information of intra-axial tumor contours and adjacent PT, results in surgical trajectory optimization initially, and maximal safe tumor resection finally. In accordance to the EPT increasing amplitude, surgeon can predict the long-term motor functional outcome.

Superparamagnetic iron oxide nanoparticles drive miR-485-5p inhibition in glioma stem cells by silencing Tie1 expression.

Gliomas are highly malignant nervous system tumours. Studies shown that cancer stem cells are one of the main reasons underlying recurrence, metastasis, and poor prognosis in glioma cases. Our previous studies have found that superparamagnetic iron oxide nanoparticles (SPIONs) can act as nucleic acid carriers to drive intracellular overexpression of these nucleic acids. In this study, CD44+/CD133+ glioma stem cells (HuGSCs) were first isolated from surgically resected tissues from patients. qPCR and western blot results showed that Tie1 expression in HuGSCs was significantly higher thanexpression in CD44-/CD133- glioma cells. Bioinformatic analysis and luciferase reporter assays showed that miR-485-5p binds to specific loci on the 3'-UTR of Tie1 mRNA to inhibit Tie1 expression. Subsequently, miR-485-5p/miR-mut and SPION complexes were transfected into HuGSCs. Transmission electron microscopy showed that a highly dense metallic electron cloud is present in HuGSCs. At the same time, in vivo and in vitro studies showed that miR-485-5p@SPIONs can significantly inhibit HuGSC proliferation, invasion, tumourigenicity, and angiogenesis. In-depth analysis showed that Tie1 interacts with neuronal growth factors such as FGF2, BDNF, GDNF, and GFAP. qPCR and western blot results showed that in miR-485-5p@SPIONs-HuGSCs, the expression levels of Tie1 and stem cell markers (Oct4, Sox2, Nanog, CD44, and CD133), and even FGF2, BDNF, GDNF, and GFAP were significantly lower than thelevels in the control group (miR-mut@SPIONs-HuGSCs). Therefore, this study showedthat Tie1 is an important factor that maintains glioma stem cell activity. SPIONs drive miR-485-5p overexpression in cells and inhibit endogenous Tie1 expression to downregulate the protein expression levels of Fgf2/GDNF/GFAP/BDNF and significantly weaken the in vivo and in vitro viability of gliomas.

Brainstem Tumor Resection via Occipital Interhemispheric Transtentorial Infracollicular Approach: 2-Dimensional Operative Video.

A brainstem tumor located at the upper pons or pontomesencephalic region is surgically challenging because of the deep-seated location and difficulty to approach, especially if the lesion is intra-axial and extends anteriorly without appearing on the pia surface. In our experience, the infracollicular entry point is feasible for such lesions and can be approached by an occipital interhemispheric transtentorial corridor through a straightforward trajectory, which ensures surgical ergonomics. Herein, we present a case of a 55-yr-old woman with a pontomesencephalic lesion removed via an occipital interhemispheric transtentorial infracollicular approach. Informed consent was obtained from the patient. Her preoperative medical course and radiological findings strongly indicated the lesion as a brainstem cavernous malformation. Although the overlying brainstem parenchyma was thin, the lesion did not appear on the pial surface. The lesion was removed via an occipital interhemispheric transtentorial infracollicular approach. During the operation, the lesion was observed to have an old hemorrhagic component and an obvious gliotic boundary, resembling the typical macropathology of a brainstem cavernous malformation. We easily dissected the lesion circumferentially off the brainstem parenchyma after thorough debulking, and a gross total resection was performed en bloc. However, postoperative pathology confirmed a diagnosis of a metastatic neuroendocrine tumor, and further systematic examination revealed cancerous lesions in the lungs. The patient experienced slight hypophrasia but recovered within 3 d postoperatively and then was discharged for further treatment. This case demonstrates the safety and efficacy of an occipital interhemispheric transtentorial infracollicular approach for brainstem tumor resection.

Fully Endoscopic Supracerebellar Infratentorial Approach for Resection of Third Ventricle Germ Cell Tumor: 2-Dimensional Operative Video.

Pineal tumor that extends into the posterior portion of the third ventricle is extremely deep-seated and surgically challenging. Various microscopic approaches have been introduced to acquire access to the posterior third ventricle, but still the exposure and visualization are relatively unfavorable. However, recently the application of high-definition endoscope gave neurosurgeons a much more magnified and clearer view of anatomy around the pineal region and third ventricle. The widely used supracerebellar infratentorial approach has been proven to offer a sufficient surgical corridor for fully endoscopic surgery for pineal tumor. We presented a case of a 13-yr-old male child with a posterior third ventricle tumor, which was surgically resected fully with the endoscope. An informed consent has been obtained from the patient and his guardians. In order to gain enough auto-retraction by gravity, diminish the pitfalls of the semisitting position, and enhance the surgeon's ergonomics, the patient was positioned with a modified "head-up" park bench position (the upper body was elevated and the head was slightly extended instead of anteflexion). The tumor was approached through suboccipital midline supracerebellar infratentorial trajectory. The superficial and deep drainage veins above the vermis were sacrificed and the quadrigeminal cistern was entered to expose the tumor. The first and the most important step of the operation was to de-vascularize the tumor bilaterally, then the tumor could be debulked and circumferentially resected. The gross total resection was achieved. Fully endoscopic supracerebellar infratentorial approach is feasible and efficient when addressing lesions located at the posterior portion of the third ventricle.

Intra-Extracranial Primary Clear Cell Sarcoma: The First Report and Review of the Literature.

BACKGROUND: Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor with poor prognosis owing to metastasis and insensitive response to chemotherapy and radiotherapy. METHODS: We first searched PubMed and Embase using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," "head," and "neck." In the 15 articles selected for literature review, only 27% (4/15) of patients were diagnosed with primary CCS of the head. Pathologically, those tumors arose from either the scalp or the superficial temporal fascia, but none invaded the skull and brain. Next, the search was performed in the same database using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," and "bone," and only 24 articles were selected. RESULTS: In the case reported here, a 36-year-old woman was found to have a palpable mass located at the left temporal-occipital region, and surgical finding confirmed the invasion into the skull and the brain. The diagnosis of primary CCS was made because of the detection of t(12;22)(q13;q12) in >50% of tumor cells by fluorescence in situ hybridization, and metastasis to the lymph nodes and lungs was discovered by postoperative positron emission tomography-computed tomography. CONCLUSIONS: To the best of our knowledge, this is the first case of primary central nervous system CCS. Primary CCS may involve the skull and should be one of the differential diagnoses for intra-extracranial communicating tumors. Further research on biological characteristics and molecular targeted therapy of CCS are needed to improve its poor prognosis.

Thalamus Cavernous Malformation Resection of via Contralateral Anterior Interhemispheric Transcallosal Approach: Two-Dimensional Operative Video.

Thalamic cavernous malformations (CM) are highly challenging surgically. In this illustrative video (Video 1), we present the case of a 36-year-old man with a CM at the left medial thalamus, which was successfully treated by a contralateral anterior interhemispheric transcallosal approach. Informed consent was obtained from the patient. Preoperative imaging demonstrated that the CM appeared to have reached the pial surface superiorly and medially, and diffusion tensor imaging showed the pyramidal tracts to be traveling laterally to the CM. Based on the "Two-point" principle and to avoid pyramidal tract impingement, an anterior interhemispheric transcallosal approach was chosen. Furthermore, to avoid excessive retraction on the ipsilateral hemisphere, we selected the contralateral trajectory over the ipsilateral trajectory. The head was positioned with the right side down; thus, the space between the right hemisphere and the falx could expand because of gravity autoretraction, which could minimize the need of retraction during the interhemispheric dissection. A small incision on the corpus callosum was performed under the guidance of neuronavigation, and the left ventricle was subsequently entered. After a thin layer of hemosiderin-stained pia was opened on the superior surface of the left thalamus, some sandlike old hemorrhagic component was removed for decompression, and the lesion was carefully dissected away from the normal parenchyma within the surrounding gliosis boundary. The CM was removed en bloc, and the deep venous anomaly was well protected. The patient did not experience any intraoperative changes shown by electrophysiologic monitoring, and he recovered well postoperatively.

MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals.

MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat. However, it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia. Here, we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage. We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1). In contrast, miR-365 antagomir alleviated both the brain injury and OXR1 reduction. Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3'-untranslated region of Oxr1. Furthermore, knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir. Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression, while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.

Epidermoid cysts of the cavernous sinus: clinical features, surgical outcomes, and literature review.

OBJECTIVE: Epidermoid cysts of the cavernous sinus (CS) are rare, and no large case series of these lesions has been reported. In this study, the authors retrospectively reviewed the outcomes of the surgical management of CS epidermoid cysts undertaken at their center and performed a review of any such cysts reported in the literature over the past 40 years. METHODS: Clinical data were obtained on 31 patients with CS epidermoid cysts that had been surgically treated at the authors' hospital between 2001 and 2016. The patients' medical records, imaging data, and follow-up outcomes were retrospectively analyzed. The related literature from the past 40 years (18 articles, 20 patients) was also evaluated. RESULTS: The most common chief complaints were facial numbness or hypesthesia (64.5%), absent corneal reflex (45.2%), and abducens or oculomotor nerve deficit (35.5%). On MRI, 51.6% of the epidermoid cysts showed low T1 signals and equal or high T2 signals. In the other lesions, the radiological findings varied considerably given differences in the composition of the cysts. Surgery was performed via the extradural approach (58.1%), intradural approach (32.3%), or a combined approach (9.7%). After the operation, symptoms remained similar or improved in 90.3% of patients and new oculomotor paralysis developed after the operation in 9.7% of patients. Seven patients (22.6%) developed meningitis postoperatively (5 aseptic and 2 septic), and all of them recovered. All patients achieved good recovery before discharge (Karnofsky Performance Status score ≥ 70). Over an average follow-up of 4.6 ± 3.0 years in 25 patients (80.6%), no recurrence or reoperation occurred, regardless of whether total or subtotal resection of the capsule had been achieved. CONCLUSIONS: Both the extradural and intradural approaches can enable satisfactory lesion resection. A favorable prognosis and symptomatic improvement can be expected after both total and subtotal capsule resections. Total capsule resection is encouraged to minimize the possibility of recurrence provided that the resection can be safely performed.

Magnetofection Based on Superparamagnetic Iron Oxide Nanoparticles Weakens Glioma Stem Cell Proliferation and Invasion by Mediating High Expression of MicroRNA-374a.

Glioma stem cells belong to a special subpopulation of glioma cells that are characterized by strong proliferation, invasion and drug resistance capabilities. Magnetic nanoparticles are nanoscale biological materials with magnetic properties. In this study, CD133(+) primary glioma stem cells were isolated from patients and cultured. Then, magnetic nanoparticles were used to mediate the transfection and expression of a microRNA-374a overexpression plasmid in the glioma stem cells. Transmission electron microscopy detected the presence of significant magnetic nanoparticle substances within the CD133(+) glioma stem cells after transfection. The qRT-PCR and Northern blot results showed that the magnetic nanoparticles could be used to achieve the transfection of the microRNA-374a overexpression plasmid into glioma stem cells and the efficient expression of mature microRNA-374a. The MTT and flow cytometry results showed that the proliferation inhibition rate was significantly higher in cells from the microRNA-374a transfection group than in cells from the microRNA-mut transfection group; additionally, the former cells presented significant cell cycle arrest. The Transwell experiments confirmed that the overexpression of microRNA-374a could significantly reduce the invasiveness of CD133(+) glioma stem cells. Moreover, the high expression of microRNA-374a mediated by the magnetic nanoparticles effectively reduced the tumourigenicity of CD133(+) glioma stem cells in nude mice. The luciferase assays revealed that mature microRNA-374a fragments could bind to the 3'UTR of Neuritin (NRN1), thereby interfering with Neuritin mRNA expression. The qRT-PCR and Western blotting results showed that the overexpression of microRNA-374a significantly reduced the expression of genes such as NRN1, CCND1, CDK4 and Ki67 in glioma stem cells. Thus, magnetic nanoparticles can efficiently mediate the transfection and expression of microRNA expression plasmids in mammalian cells. The overexpression of microRNA-374a can effectively silence NRN1 expression, thereby inhibiting the proliferation, invasion and in vivo tumourigenicity of human glioma stem cells.

Clinical experience of 3T intraoperative magnetic resonance imaging integrated neurosurgical suite in Shanghai Huashan Hospital.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI (< 1.0T). This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital, Shanghai, China. METHODS: From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency. RESULTS: All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas (n = 161) was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients (12.42%) suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients (3.16%). Twenty-one of 161 patients (13.04%) had early speech deficit and late speech deficit was only observed in six of 158 patients (3.80%). The ratio of gross total resection for pituitary adenomas (n = 49) was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy. CONCLUSION: The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.

Surgical strategies in treating brainstem cavernous malformations.

BACKGROUND: Optimal therapy of brainstem cavernous malformations (BSCMs) remains controversial because their biological behavior is unpredictable and surgical removal is challenging. OBJECTIVE: To analyze our experience with BSCMs and to conduct a review of the literature to identify a rational approach to the management of these lesions. METHODS: Fifty-five patients harboring 57 BSCMs underwent surgery and 17 patients were treated conservatively during the 10-year period from 1999 to 2008. The operative strategy was to perform complete CM resection and to preserve any associated venous malformation with minimal functional brainstem tissue sacrificed. The National Institutes of Health Strength Scale (NIHSS) was used to assess neurological status. RESULTS: The average hemorrhagic and rehemorrhagic rates were 4.7% and 32.7% per patient-year, respectively. Total lesional resection was achieved in all operated patients. Their mean NIHSS score was 4.6 after the first episode, 3.5 preoperatively, 3.2 at discharge, and 1.4 after a mean follow-up of 49 months. Complete recovery rates of motor deficits and sensory disturbances from the preoperative state were 70.4% and 51.7%, respectively. Complete recovery rates for cranial nerves III, V, VI, and VII and the lower group were 60%, 63.2%, 25%, 57.1%, and 80%, respectively. For the conservative patients, the mean NIHSS score was 5.9 after the first episode and 1.7 after a mean follow-up of 40 months. CONCLUSION: NIHSS is optimal for evaluating the natural history and surgical effect of patients harboring BSCMs. Surgical resection remains the primary therapeutic option after careful patient screening and preoperative planning.