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Objectives This study aimed to generate mutant mice containing the Acvrl1 gene flanked with LoxP sequences to allow conditional deletion of Acvrl1 by the LoxP/Cre system. Such mice may facilitate the development of brain arteriovenous malformation (BAVM) models. Methods The CRISPR/Cas9 technique was used to edit Acvrl1 . Two single guide RNAs (sgRNAs) with recognition sites on intron 3 and 8 and a donor vector that was homologous with the targeted gene and contained two LoxP sequences were designed and constructed. The in vitro -synthesized sgRNA, Cas9 mRNA and donor vectors were injected into mouse zygotes, which were then transferred into pseudopregnant mice. Neonatal mutant mice were identified by genotyping and sequencing. Results Two mice with a floxed Acvrl1 allele were generated at a success rate of 8.7%. The target mice, which were healthy and fertile, were obtained through interbreeding. Conclusion CRISPR/Cas9 is a reliable gene-editing tool, and is able to efficiently modify Acvrl1 and create the target mice. [ABSTRACT FROM AUTHOR]

Background Intraoperative ultrasonography is widely used in neurosurgery for the management of intracerebral hematoma and brain tumor. However, the clinical value of this method in the surgery of cerebral arteriovenous malformations (AVMs) has not been reported. In this study, the application of intraoperative ultrasonography for AVM surgery was evaluated prospectively. Methods This prospective clinical study comprised 41 patients who underwent microsurgical resection of cerebral AVMs at our institute. After routine craniotomy, ultrasonographic imaging with color Doppler ultrasonography and real-time contrast-enhanced ultrasonographic angiography if necessary were applied as navigated images on the monitor during the operation. Results Ultrasonographic imaging made it easier to understand the vascular architecture during the operation. Color Doppler flow imaging clearly delineated the shape and margin of the AVMs. Intraoperative real-time contrast-enhanced ultrasonographic angiography enabled the surgeons to categorically identify AVM feeders both on the surface and deep in the tissue. Conclusions Microneurosurgery with intraoperative ultrasonographic image guidance was a safe, effective, and reliable method for identifying the afferent and efferent vessels and for confirming the complete resection of AVMs. These benefits of image-guided microsurgery were mostly apparent for deep-seated AVMs that were not visible on the surface of the brain. [ABSTRACT FROM AUTHOR]

Purpose Aberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-β, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. Methods We enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-β, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. Results The baseline plasma VEGF content was 222.63 pg/mL (range 43.25–431.25 pg/mL). At three months post surgery, there was a significant −34.29% decline in plasma VEGF content versus baseline ( P   =  0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm 3 ) than those with a nidus volume < 10 cm 3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P  = 0.057]. The baseline plasma TGF-β content was 556.17 pg/mL (range 44.44–1486.11 pg/mL) and there was a significant −27.47% decline in plasma TGF-β content at 3 months post radiosurgery versus baseline ( P   =  0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14–453.76 pg/mL). There was an immediate and significant −12.47% decline in plasma ANG-2 content post surgery versus baseline ( P   =  0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline ( P   =  0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67–36.78 pg/mL). No significant difference in plasma bFGF content was observed immediately post surgery and 3 months post surgery versus baseline ( P   =  0.05). Conclusions Radiosurgery for brain AVM patients significantly reduced the plasma levels of angiogenic factors. The plasma angiogenic factors may be candidate markers for aberrant agniogenesis of brain AVM and patient response to radiosurgery. [ABSTRACT FROM AUTHOR]