Inhibition of Glial Activation and Subsequent Reduction in White Matter Damage through Supplementation with a Combined Extract of Wheat Bran, Citrus Peel, and Jujube in a Rat Model of Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O2) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.

Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats.

Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood-brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood-brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus.

BACKGROUND: Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH. METHODS: Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings. RESULTS: The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5 ± 5.4 versus 24.0 ± 4.5, p = 0.041; iNPHGS cognitive score: 2 ± 0.9 versus 1 ± 0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1 ± 1.0 versus 0 ± 0.9, p = 0.012; postoperative iNPHGS urinary score:1 ± 1.0 versus 0 ± 0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1 ± 0.7 versus high vitamin D group: 2 ± 0.4, p = 0.031). CONCLUSION: Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: its clinical and angiographic perspectives.

BACKGROUND: To assess the efficacy of stereotactic radiosurgery (SRS) for intracranial dural arteriovenous fistulas (DAVFs), the authors retrospectively reviewed our 7-year experience. We evaluated the obliteration rate, improvement in clinical symptoms, and complications. METHODS: Thirty patients with DAVF underwent SRS using a Gamma Knife between 2009 and 2015. Twenty-three patients were treated with SRS alone, and seven patients underwent SRS for residual or recurrent DAVFs after embolization or surgery. Chemosis, diplopia, and pulsating tinnitus were the most common symptoms. Median target volume was 2.9 cm3 (range, 0.8-13.6 cm3), and median radiation dose to the target was 17 Gy (range, 12-20 Gy). Median follow-up period was 33 months (range, 6-82 months). RESULTS: At the last neuroimaging follow-up, DAVFs were totally obliterated in 23 patients (77%) and subtotally in 7 (23%). At the last clinical follow-up, 21 patients (70%) showed complete recovery, and 9 (30%) showed incomplete recovery in symptoms or signs. None experienced worsening symptoms or signs. Asymptomatic perilesional edema after SRS occurred in one patient (3%). Total obliteration rates after SRS were 43% at 1 year, 79% at 2 years, and 95% at 5 years. Improvement rates of neurological function after SRS were 12% at 1 month, 52% at 2 months, 72% at 3 months, and 96% at 6 months. A multivariate analysis revealed that Borden type 1 (p = 0.019, hazard ratio, 3.254, 95% confidence interval, 1.216-8.707) was significantly associated with symptom improvement. CONCLUSIONS: SRS for intracranial DAVFs provided a high obliteration rate and a relatively low risk of radiation-induced complications. In selected benign cases without cortical venous drainage, SRS is a safe and effective treatment for symptom relief and fistula obliteration, even though the time course of improvement is longer than those of embolization and surgery.

The clinical significance of fascin expression in a newly diagnosed primary glioblastoma.

The actin-binding protein fascin has been associated with clinically aggressive tumors and poor prognosis. The purpose of this study was to investigate possibility of fascin expression as a prognostic factor in a newly diagnosed primary glioblastoma (GBM). Between July 2007 and December 2013, 37 out of 126 patients diagnosed with GBM satisfied the following inclusion criteria: (1) the presence of immunohistochemically-available tissue, (2) a new primary GBM, (3) gross-total resection, and (4) standardized adjuvant treatment, known as the Stupp regimen. The median follow-up period was 18 months (range 5-95). According to the staining intensity of fascin, progression-free survival (PFS) in the low-intensity fascin group (median PFS 9.0 months; 95 % CI 6.0-12.0) was longer than PFS in the high-intensity fascin group (median PFS 7.0 months; 95 % CI 5.6-10.4; p = 0.024). Overall survival (OS) in the low-intensity fascin group (median OS 20.0 months; 95 % CI 17.7-22.4) was longer than OS in the high-intensity fascin group (median OS 13.0 months; 95 % CI 8.2-17.8; p = 0.031). And, the staining intensity of fascin was a statistically significant factor in PFS and OS according to univariate and multivariate analyses (univariate analysis p = 0.043 and p = 0.043; multivariate analysis p = 0.041 and p = 0.044). Our clinical study showed that fascin expression intensity may be correlated with clinical outcomes of a newly diagnosed primary GBM, especially with regard to PFS and OS.

Pituitary carcinoma with fourth ventricle metastasis: treatment by excision and Gamma-knife radiosurgery.

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Border Zone Maybe Correlated with Radiation Necrosis After Radiosurgery in Metastatic Brain Tumor.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) in brain metastases has been extensively evaluated, and RN is correlated with various risk factors. However, no study comprehensively analyzed the correlation between RN and the border zones of the brain that are vulnerable to ischemia. We hypothesized that patients with tumors in the border zone are at high risk of RN. Hence, the current study aimed to assess the correlation between border zone lesions and RN, with consideration of other predetermined factors. METHODS: This retrospective study included 117 patients with 290 lesions who underwent Gamma Knife SRS. Radiological and clinical analyses were performed to identify factors possibly correlated with RN. Notably, the lesion location was classified into 2 groups (border zone and nonborder zone) based on the blood supply. RESULTS: In total, 22 (18.8%) patients with 22 (7.5%) lesions developed RN. Univariate analysis revealed a significant correlation between RN and external border zone lesions, second course of SRS administered at the same site of the previous SRS, prescribed dose, and tumor volume. Multivariate analysis showed that border zone lesions, second course of SRS at the same site of the previous SRS, and tumor volume were significantly correlated with RN. CONCLUSIONS: Patients with tumors in the border zone are at high risk of RN. The potential risks of RN can be attributed hypothetically to hypoperfusion. Hence, the association between RN and border zone lesions seems reasonable.

Switching strategy for mechanical thrombectomy of acute large vessel occlusion in the anterior circulation.

BACKGROUND AND PURPOSE: We introduce the concept of a switching strategy for mechanical thrombectomy with period-to-period analysis. In period 1, forced arterial suction thrombectomy with a Penumbra reperfusion catheter was performed, even in difficult cases; in period 2, forced arterial suction thrombectomy was initially performed, with switching to Solitaire in difficult cases. METHODS: We analyzed 135 consecutive patients treated with mechanical thrombectomy with acute large vessel occlusion in the anterior circulation, 61 from period 1 and 74 from period 2. We defined difficult case for both periods as ≥3 failed attempts at recanalization. RESULTS: Period 2 showed a trend for better angiographic outcome of Thrombolysis in Cerebral Infarction 2b-3 (73.8%, period 1 versus 85.1%, period 2; P=0.10). In interperiod subgroup analysis of difficult cases, switching significantly outperformed nonswitching in Thrombolysis in Cerebral Infarction 2b-3 recanalization (52.7% versus 82.9%; P=0.030). Differences in puncture-to-recanalization time, symptomatic intracranial hemorrhage incidence, and procedure-related complications were not statistically significant. CONCLUSIONS: A switching strategy using 2 mechanical thrombectomy techniques (forced arterial suction thrombectomy to Solitaire) may harbor better angiographic outcomes than a 1 technique only strategy (forced arterial suction thrombectomy).

Rescue strategy for acute carotid stent thrombosis during carotid stenting with distal filter protection using forced arterial suction thrombectomy with a reperfusion catheter of the Penumbra System: a technical note.

BACKGROUND: Among the procedural complications related to carotid artery stenting (CAS), internal carotid artery (ICA) flow arrest is one of the most drastic complications, as it can cause major ischemic stroke. Acute carotid stent thrombosis (ACST) is a rare etiology of ICA flow arrest during carotid artery stenting with distal filter protection, but the most devastating. Moreover, no definitive management strategy has been established so far for treating ACST. METHODS: We introduce a rescue management strategy for differential diagnosis of ICA flow arrest and for recanalization of ACST with a simple endovascular mechanical thrombectomy technique. RESULTS: In three cases of ICA flow arrest caused by ACST, selective angiography with a 1.7 F microcatheter provided confirmative diagnosis. Recanalization was then achieved with a Penumbra System (PS) reperfusion catheter using the forced arterial suction thrombectomy (FAST) technique. Successful recanalization with a Thrombolysis In Cerebral Infarction score of 3 was achieved for all three patients. Recanalization was confirmed with follow-up angiography at least 24 h after the procedure. No complications associated with this technique occurred. CONCLUSIONS: Based on our preliminary experiences, selective microangiography can be helpful for rapid diagnosis of ACST, and the present mechanical thrombectomy technique, using a modification of the PS, can play a role in adjuvant management or as a last resort for the treatment of ACST during CAS.

Intramedullary spinal cord metastasis in renal cell carcinoma: a case report of the surgical experience.

Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is rare manifestation and most of them are treated by adjuvant treatment modalities like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy has been preferred as the first-line treatment modality of ISCM from RCC and only a few cases underwent surgical treatment. We describe a case of ISCM from RCC, which underwent surgical excision and pathologically confirmed. A 44-yr-old man was presented with rapid deterioration of motor weakness during focal radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass and spinal cord decompression, his motor power was dramatically improved to ambulate by himself. We report the first published Korean case of ISCM from RCC confirmed pathologically and describe our surgical experience and his clinical characteristics.

Venous ectasia preceding intra-tumoral hemorrhage in a case of gliosarcoma with transverse sinus involvement.

Although intratumoral hemorrhage is common in patients with malignant brain tumors, reports on its clinical course are scarce. This report presents a rare case of a patient with intratumoral hemorrhage with gliosarcoma invading the venus sinus. This invasion and a small draining vein were observed at diagnosis. Magnetic resonance imaging performed 1 week later showed new-onset venous ectasia, which caused intratumoral hemorrhage. This case provides insight into the mechanisms underlying intratumoral hemorrhage and highlights the emergence of new intratumoral vasculature as a potential warning sign for hemorrhage.

Neuromyelitis Optica Spectrum Disorders Mimicking Multiple Brain Tumors.

We report a rare case of neuromyelitis optica spectrum disorders (NMOSD), mimicking multiple brain tumors. A 53-year-old woman presented with weakness and paresthesia in her right arm and leg. Upon admission, brain MRI showed about 10 multiple brain tumors, which had to be differentiated from multiple brain metastases, lymphoma, and high-grade glioma in both hemispheres. No primary cancer was found in the chest-abdomen-pelvis CT. Subsequent spine MRI revealed multifocal cord signal change involving C2-T7, suggesting myelitis. A decrease in visual acuity was noted when taking a medical history, and optic neuritis was diagnosed upon ophthalmologic examination. With clinical and radiological appearances, multiple brain and spinal cord lesions have been diagnosed as NMOSD. Steroid and immunosuppressive drugs were administered. We should consider the possibility of an autoimmune disease, such as NMOSD, involving the optic nerve, spinal cord, and central nervous system when multiple hemispheric tumefactive lesions are observed.

Arrested Pneumatization of the Sphenoid Sinus in the Skull Base.

We report 2 cases of arrested pneumatization of the sphenoid sinus, a normal variant commonly misdiagnosed as a serious condition of the skull base. A 65-year-old man visited a local clinic for regular checkups. Brain CT showed a non-expansile lesion of the soft tissue with a well-defined sclerotic margin in the clivus but without destruction or mass effect on the surrounding bony structures. Subsequent brain MRI revealed that the lesion within the clivus was a high-signal lesion on the T2-weighted image, containing a low-signal round mass seen on a high-intensity signal on the T1-weighted image without contrast enhancement. Thus, the lesion was considered to contain internal fat. A 70-year-old woman diagnosed with a tumor in the greater sphenoid bone visited our hospital. Her brain CT revealed a non-expansile lesion of mixed density and a well-demarcated lesion and internal curvilinear calcification in the left greater wing of the sphenoid bone. The margin was osteosclerotic and the adjacent bony structure was intact. Her brain MRI showed that the lesion within the greater sphenoid bone had multiple low-signal lesions within a high-signal lesion on the T2-weighted image, suggesting internal fat contents. The lesions were diagnosed as arrested pneumatization of the sphenoid sinus and no further examination or treatment was performed. Arrested pneumatization of the sphenoid sinus should be considered in the presence of non-expansile lesion with an osteosclerotic boundary and internal fat component in the skull base.

Spindle cell oncocytoma of the sella turcica with anaplastic features and rapid progression in short-term follow-up: a case report with proposal of distinctive radiologic features.

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

Effect of Cadherin-11 Expression on the Prognosis of a Newly Diagnosed Primary Glioblastoma.

BACKGROUND: Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). METHODS: Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. RESULTS: In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). CONCLUSION: Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

Factors related to the local treatment failure of γ knife surgery for metastatic brain tumors.

PURPOSE: Radiosurgery (RS) is regarded as a standard therapy for metastatic brain tumors, but local failure requiring repeated therapy for the same lesion remains an unsolved problem. The authors analyzed outcomes of gamma knife surgery (GKS) for metastatic lesions to identify factors of local treatment failure. MATERIALS AND METHODS: The hospital records of 103 patients with a metastatic brain tumor and monitored for more than 6 months were analyzed. Lesion response to RS was analyzed in 77 patients with available gamma plan data. Local treatment failure was defined as lesion regrowth or repeat GKS within 6 months. In cases with multiple lesions, largest masses were evaluated. Primary sites, metastatic location, Karnofsky scale, tumor size, number of metastatic lesions, and various radiosurgical prescription parameters, namely, Paddick's conformity index (CI), Radiation Therapy Oncology Group (RTOG)-CI, and gradient index, were analyzed. RESULTS: Of the 103 study subjects, 58 were male and 45 were female. Primary sites were lung (n = 58), breast (n = 12), colon (n = 6), kidney (n = 7), rectum (n = 6), and others (n = 14). Median survival duration from the diagnosis of brain metastasis was 25 months. Local treatment failure occurred in 14 of 77 the patients (77 lesions) with available gamma plan data. A lung cancer primary site was found to have a lower GKS failure rate than a breast or a renal site (p < 0.05). Lesions with a high Paddicks' CI or a low RTOG-CI had a higher rate of treatment failure (p < 0.05). Multivariate analysis revealed that primary tumor site and Paddick's CI were related to treatment failure (p < 0.05). CONCLUSION: Brain metastases from renal and breast cancers had higher rates of local GKS treatment failure than those from lung cancer. Furthermore, high Paddick's CI revealed higher rate of local recurrence, and was not contributory to prevent local treatment failure. However, the enlargement of the diameter of the tumor after RS in the early follow-up period does not necessarily represent the poor outcome or need of retreatment.

The retrogasserian zone versus dorsal root entry zone: comparison of two targeting techniques of gamma knife radiosurgery for trigeminal neuralgia.

BACKGROUND: We performed a comparative study of the retrogasserian zone (RGZ) with the dorsal root entry zone (DREZ) target to determine effective gamma knife radiosurgery (GKRS) technique in patients with medically refractory trigeminal neuralgia (TN). METHODS: We retrospectively reviewed the records of 39 patients with refractory TN undergoing GKRS between April 2005 and October 2008. Until October 2007, DREZ was used as the primary target point. Since November 2007, RGZ has been targeted, located anterior to DREZ. The pain outcome of patient, pain recurrence, and treatment-related complications were evaluated. FINDINGS: Using the Barrow Neurologic Index (BNI) pain score, 15 (93.8%) RGZ and 20 (87.0%) DREZ cases achieved treatment success (BNI pain score I-IIIb) (p = 0.631). Seven (43.8%) RGZ and four (17.4%) DREZ patients reported complete pain relief without medications (BNI pain score I). The time to a response after the GKRS was significantly shorter in the RGZ group (mean 4.1 weeks) than in the DREZ group (mean 6.4 weeks) (p = 0.044). The total complication rate (25.0%) in the RGZ group was similar to the DREZ group (26.1%); however, frequency of bothersome facial numbness and dry eye syndrome was lower in the RGZ group (0%, 0%) compared to the DREZ group (13.1%, 8.7%) (p = 0.255 and 0.503). CONCLUSIONS: The RGZ targeting technique in the GKRS for TN had a better treatment success, with fewer bothersome complications compared to the DREZ target.

Sinonasal Teratocarcinosarcoma, a Rare Tumor Involving Both the Nasal Cavity and the Cranial Cavity.

Sinonasal teratocarcinosarcoma (SNTCS), a very rare tumor, is known to be a heterogeneous with epithelial, mesenchymal, and neuroepithelial components and shows a very aggressive clinical course. Due to the heterogeneity of this tumor, it is often misdiagnosed. No definitive treatment modality has been reported because it is a very rare tumor. A 44-year-old man presented to a rhinologist with headache and nasal obstruction, and an intranasal tumor was found that invaded into the cranial cavity. He underwent combined surgery with a rhinologist and a neurosurgeon following cognitive decline that worsened after a transnasal biopsy. The patient was diagnosed with SNTCS and underwent radiotherapy. However, residual tumor was found during radiotherapy and additional chemotherapy was administered. Follow-up brain MRI revealed no remnant or recurrent lesion. SNTCS is a tumor that has not yet been well researched and should be further investigated for proper treatment.

Studies of combined NO-eluting/CD47-modified polyurethane surfaces for synergistic enhancement of biocompatibility.

The blood compatibility of various intravascular (IV) devices (e.g., catheters, sensors, etc.) is compromised by activation of platelets that can cause thrombus formation and device failure. Such devices also carry a high risk of microbial infection. Recently, nitric oxide (NO) releasing polymers/devices have been proposed to reduce these clinical problems. CD47, a ubiquitously expressed transmembrane protein with proven anti-inflammation/anti-platelet properties when immobilized on polymeric surfaces, is a good candidate to complement NO release in both effectiveness and longevity. In this work, we successfully appended CD47 peptides (pepCD47) to the surface of biomedical grade polyurethane (PU) copolymers. SIRPα binding and THP-1 cell attachment experiments strongly suggested that the pepCD47 retains its biological properties when bound to PU films. In spite of the potentially high reactivity of NO toward various amino acid residues in CD47, the efficacy of surface-immobilized pepCD47 to prevent inflammatory cell attachment was not inhibited after being subjected to a high flux of NO for three days, demonstrating excellent compatibility of the two species. We further constructed a CD47 surface immobilized silicone tubing filled with NO releasing S-nitrosoglutathione/ascorbic acid (GSNO/AA) solution for synergistic biocompatibility evaluation. Via an ex vivo Chandler loop model, we demonstrate for the first time that NO release and CD47 modification could function synergistically at the blood/material interface and produce greatly enhanced anti-inflammatory/anti-platelet effects. This concept should be readily implementable to create a new generation of thromboresistant/antimicrobial implantable devices.