CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage.

Aims: Subarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-studied post-SAH. The current study aims to determine whether anti-CD47 treatment can enhance blood clearance after experimental SAH. Methods: The prechiasmatic blood injection model of SAH was used in mice. Mice were either treated with the CD47-blocking antibody or IgG as control. The effect of the anti-CD47 antibody on blood clearance and neurological function following SAH was determined. Neuroinflammation and neuronal injury were compared between the treatment and control samples on day 1 and day 7 after SAH using flow cytometry, immunofluorescence, Fluoro-Jade C, and Nissl staining, RT-PCR, and Western blot analysis. Results: CD47-blocking antibody sped-up blood clearance after SAH, and resulted in less neuronal injury and neurological deficits than control samples. Microglia played a role in the anti-CD47 blockade. Following SAH Following SAH, CD47 antibody-treated mice had less neuroinflammation and lower levels of apoptosis compared to controls and both one and 7 days. Conclusions: CD47 antibody treatment has a neuroprotective effect following SAH, by increasing blood clearance rate and reducing brain injury. These findings suggest CD47 antibody treatment may improve SAH patient outcomes.

Comparision of Mechanical Thrombectomy With Contact Aspiration or Stent Retriever in Patients With Large-vessel Occlusion in Acute Ischemic Stroke.

OBJECTIVES: Whether the direct aspiration approach of thrombectomy for recanalization in patients with acute ischemic stroke has a similar efficacy and safety compared to the stent-retriever still remains uncertain. METHODS: A retrospective data analysis was performed to identify patients with large cerebral artery acute ischemic stroke treated with endovascular thrombectomy. The study was conducted between January 2018 and December 2019 in a single stroke center. RESULTS: Twenty patients met inclusion criteria for this study with a mean age 66.64 ±â€Š17.92 years' old. The symptom occurred on the left side were in 13, and the right side in 7. The location of occlusion was 8 in M1 of the middle cerebral artery of M2, and 6 in internal carotid artery. Nine patients were randomized to first-line treatment with contact aspiration and eleven to first-line treatment with a stent retriever. The mean time from admission time to groin puncture was 55.51 ±â€Š31.03 minutes. The average time from groin puncture to maximal revascularizion after mechanical thrombectomy was 50.9 ±â€Š22.5 minutes in contact aspiration group, but this time was 71.37 ±â€Š25.45 minutes in the group of stent retriever. The overall successful revascularization rate (TICI 2b-3) was 88.9% in contact aspiration (TICI2a = 1, TICI 2b = 4 patients, TICI 3 = 4 patients), and 90.1% in stent retriever (TICI2a = 1, TICI 2b = 6 patients, TICI 3 = 4 patients). DISCUSSION: First-line thrombectomy with contact aspiration did not result in a higher successful revascularization rate at the end of the procedure but had a short time from groin puncture to maximal revascularizion.

Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma.

AIM: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma. METHODS: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit. RESULTS: The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29mo (range, 7-36mo). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation (n=2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy (n=13; 43%), mild lens opacity (n=7; 23%), vitreous hemorrhage (n=5; 17%) and rhegmatogenous retinal detachment (n=1; 3%). No extraocular tumor extension or metastasis occurred. CONCLUSION: Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma.

Analysis of Peripheral Blood Cells' Transcriptome in Patients With Subarachnoid Hemorrhage From Ruptured Aneurysm Reveals Potential Biomarkers.

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon disease. Considering ruptured intracranial aneurysms as the main cause of this disease and only a minority of the intracranial aneurysms will rupture sooner or later, to understand the underlying pathology or a specific gene expression profile of an impending ruptured intracranial aneurysm is of great importance. METHODS: The transcriptome in peripheral blood cells of patients with SAH from ruptured aneurysm was compared with that of control patients suffering from headaches. The microarray dataset GSE36791 comprised 43 patients with SAH from ruptured aneurysms and 18 control patients. Differential expression analysis was performed with the R language packages to identify differentially expressed genes (DEGs). Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway database analysis were performed to identify significantly altered biological functions and pathways, respectively. The protein-protein interaction networks were constructed with information from the STRING database. RESULTS: A total of 528 DEGs were identified, of which 311 were upregulated and 217 downregulated. Clustering analysis confirmed that these genes can distinguish ruptured aneurysm SAH patients from the control patients. The DEGs were mainly enriched for immune/inflammation response and related pathways. Among the DEGs, 8 genes (ARG1, MAPK14, RPS2, SPI1, FYN, CEBPB, FLOT1, and CD4) were identified as the key regulators in the Protein-Protein Interaction network. MAPK14, CEBPB, FLOT1, and CD4 might be potential biomarkers of SAH. CONCLUSION: This study identified a range of DEGs SAH patients with ruptured aneurysms, which may enhance our current knowledge on this disease and may provide potential biomarkers of this disease.

Neuroprotection by intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats in a model of ischemic stroke.

Our previous studies showed that bone marrow mononuclear cells (BMMNCs) from 5-fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to further explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in the same model. Rats were intravenously pre-treated with 5-FU, and BMRMNCs were collected 7 days later and subjected to flow cytometry for detection of CD34, CD45 and CD90. Middle cerebral artery occlusion (MCAO) was induced in rats, and BMMNCs and BMRMNCs were independently transplanted via the tail vein at 24 h after MCAO. NISSL staining was performed 14 days after cell transplantation and the viable cells in the hippocampus were counted. Stromal cell-derived factor 1 (SDF-1) mRNA expression was detected in the penumbra at 7 and 14 days after treatment. The contents of pro-inflammatory cytokines and growth factors as well as microvessel density (MVD) were determined at 14 days. Results showed more BMRMNCs were positive for CD34, CD45 and CD90. After transplantation, more viable cells were observed in the hippocampus of BMRMNCs treated rats. In addition, BMRMNCs transplantation significantly increased MVD, reduced pro-inflammatory cytokines and raised growth factors in the penumbra. However, the SDF-1 mRNA expression was comparable between BMRMNCs group and BMMNCs group. Our results indicate that BMRMNCs are likely to more effectively improve the local microenvironment to increase viable cells and elevate angiogenesis, exerting neuroprotective effects on cerebral ischemia in rats.

Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.

Gliomas are the most common and aggressive type of primary adult brain tumors. Although TREM2 mutation is reported to be related to Nasu-Hakola disease and Alzheimer's disease, little is known about the association between TREM2 and gliomas. Here, we reported that TREM2 was significantly overexpressed in glioma tissues compared with non-tumorous brain tissues. Furthermore, TREM2 expression was closely related to pathological grade and overall survival of patients with gliomas. Down-regulation of TREM2 in two glioma cell lines, U87 and U373, resulted in a significant reduction in cell proliferation, migration and invasion and a dramatic increase in S phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TREM2 expression inhibited U87 cell proliferation. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TREM2 was positive related to Kyoto Encyclopedia of Genes and Genomes (KEGG) apoptosis, Cromer metastasis and KEGG chemokine pathways, which was further validated by western blot in TREM2 knockdown glioma cells and indicated a possible mechanism underlying its effects on glioma. In summary, our study suggests that TREM2 may work as an oncogene and a new effective therapeutic target for glioma treatment.

Clear cell meningioma: clinical features, CT, and MR imaging findings in 23 patients.

BACKGROUND: Clear cell meningioma (CCM) is a rare meningioma, with radiologic features not well characterized in literature. The purpose of this study was to describe and characterize the clinical features and imaging findings of CCM. MATERIALS AND METHODS: The computed tomography (n = 16) and magnetic resonance (n = 23) images of 23 patients (12 men and 11 women; mean age, 34.6 years) were retrospectively reviewed. All of the patients underwent surgical resection. Follow-up was performed through clinical observations. RESULTS: Cerebellopontine angle was the most frequently presenting location (n = 10). The tumors were isointense (n = 12) or hypointense but associated with isointense (n = 7) appearance to gray matter on T1-weighted images. However, the tumors seemed to be isointense (n = 6) or isointense and hyperintense (n = 13) on T2-weighted images. On gadolinium-enhanced T1-weighted images, heterogeneous enhancement was seen in 14 lesions. Four lesions had amorphous calcifications, 18 showed peritumoral edema, 14 had cystic areas, 2 had bone hyperostosis, and 8 manifested bone destruction. On initial surgery, 17 patients underwent complete resection, whereas 5 patients underwent subtotal resection of their tumors. The operative result for the remaining patient was unknown. Follow-up was possible in 22 patients. Eleven patients had recurrence and 2 had died. CONCLUSIONS: Clear cell meningioma is a rare subtype of meningioma that occurs in younger patients and often recurs. Cerebellopontine angle is the most affected area in this series. The extent of initial surgical resection is the most important prognostic factor. In radiological studies, CCM tends to have marked heterogeneous enhancement, prominent peritumoral edema, intratumoral cystic components, and involvement of the adjacent bone.

The strategy of microvascular decompression for hemifacial spasm: how to decide the endpoint of an MVD surgery.

OBJECTIVE: Microvascular decompression (MVD) has become the standard treatment for hemifacial spasm. As not all patients get complete relief, this strategy is still controversial. The study aimed to figure out how to tell the proper endpoint to the surgery. METHODS: A series of 356 consecutive patients with hemifacial spasm were enrolled in this study. All patients fell into two groups according to the period they presented. Two different criteria (simple criterion vs. complex criterion) to end an operation were applied respectively. The intra-operative finding, results and complications of these two groups were compared. The advantage of the complex criterion was analyzed. RESULTS: The group which used complex criterion got better results than the group which used simple criterion. The complex criterion which combines full-length evidence, vascular evidence and electrophysiological evidence proved to be reliable to tell the proper endpoint to the surgery. CONCLUSION: MVD operations can be ended only after the full-length evidence, vascular evidence and electrophysiological evidence are all present.

A successful treatment of coexistent hemifacial spasm and trigeminal neuralgia caused by a huge cerebral arteriovenous malformation: a case report.

Regardless hemifacial spasm (HFS) or trigeminal neuralgia (TN) is commonly caused by an offending artery, 36 cases caused by an arteriovenous malformation (AVM) have been reported in the literature. However, the concurrent HFS and TN caused by AVM have never been reported so far. We reported a case of coexistent HFS-TN associated with a huge AVM, and the symptoms of both spasm and pain relieved gradually after endovascular embolization of the nidus. The etiology and pathogenesis as well as the treatment of this disorder are discussed and reviewed in the article.

Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression.

AIMS: Several lines of evidence demonstrated that endothelial nitric oxide synthase (eNOS) confers protective effects during cerebral ischemia. In this study, we explored the underlying cellular and molecular mechanisms of neuroprotection by eNOS. METHODS: A series of in vivo and in vitro ischemic models were employed to study the role of eNOS in maintaining neuronal survival and to identify the downstream factors. RESULTS: The current data showed that pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which was consistent with the findings in an oxygen-glucose deprivation model (OGD) with two neuronal cells: primary rat cortical neurons and human neuroblastoma SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was totally abolished by exogenous BDNF in both in vitro and in vivo models. On the other hand, eNOS overexpression through an adenoviral vector exerted a prominent protective effect on the neuronal cells subject to OGD, and the protective effect was totally abrogated by a neutralizing anti-BDNF antibody. CONCLUSION: Collectively, our results indicate that the neuroprotection of neuron-derived eNOS against the cerebral ischemia was mediated through the regulation of BDNF secretion. In conclusion, our discovery provides a novel explanation for the neuroprotective effect of eNOS under pathological ischemic conditions such as stroke.

A clinical analysis on microvascular decompression surgery in a series of 3000 cases.

OBJECTIVE: Despite the microvascular decompression (MVD) has become a definitive treatment for trigeminal neuralgia (TN) and hemifacial spasm (HFS), not all of the patients have been cured completely so far and this sort of operation is still with risk because of the critical operative area. In order to refine this surgery, we investigated thousands MVDs. METHODS: Among 3000 consecutive cases of MVDs have been performed in our department, 2601 were those with typical TN or HFS, who were then enrolled in this investigation. They were retrospectively analyzed with emphasis on the correlation between surgical findings and postoperative outcomes. The differences between TN and HFS cases were compared. The strategy of each surgical process of MVD was addressed. RESULTS: Postoperatively, the pain free or spasm cease occurred immediately in 88.3%. The symptoms improved at some degree in 7.2%. The symptoms unimproved at all in 4.5%. Most of those with poor outcome underwent a redo MVD in the following days. Eventually, their symptoms were then improved in 98.7% of the reoperative patients. The majority reason of the failed surgery was that the neurovascular conflict located beyond REZ or the offending veins were missed for TN, while the exact offending artery (arteriole) was missed for HFS as it located far more medially than expected. CONCLUSION: A prompt recognition of the conflict site leads to a successful MVD. To facilitate the approach, the craniotomy should be lateral enough to the sigmoid sinus. The whole intracranial nerve root should be examined and veins or arterioles should not be ignored. For TN, all the vessels contacting the nerve should be detached. For HFS, the exposure should be medial enough to the pontomedullary sulcus.

[Treatment of acute ruptured aneurysm with Guglielmi detachable coil embolization].

OBJECTIVE: To investigate the curative effect of Guglielmi detachable coil (GDC) on acute ruptured intracranial aneurysms. METHODS: The clinical data of 34 patients with acute rupture of intracranial aneurysms treated with early GDC embolization within 6 days after the rupture, 6 being of grade I, 23 of grade II, 4 of grade III and 1 of grade IV according to Hunt-Hess grading, were analyzed retrospectively. Fourteen patients were treated within 3 days, and 20 patients were treated in the 4th to 6th days after the rupture. Two cases of wide-neck aneurysm were embolized with Medtronic AVE stent supported GDC. Angiography was used to observe the effects. RESULTS: Angiography showed complete occlusion in 28 cases and 90% occlusion in 4 cases. One aneurysm was ruptured during the procedure. The caudal tip of GDC protruded to the parent vessel in 2 cases. Two cases failed to be embolized due to severe cerebrovascular spasm. There were no mortality and complications. No re-rupture occurred in the follow-up. CONCLUSION: Less invasive and with less risk and complication, early GDC embolization is one of the ideal therapeutic methods to manage acute ruptured aneurysms.