NG2 cells, also known as oligodendrocyte progenitors or polydendrocytes, are a major component of the glial scar that forms after spinal cord injury. NG2 cells react to injury by proliferating around the lesion site and differentiating into oligodendrocytes and astrocytes, but the molecular mechanism is poorly understood. In this study, we tested the role of the transcription factor STAT3, and its suppressor SOCS3, in NG2 cell proliferation and differentiation after spinal cord injury. Using knockout mice in which STAT3 or SOCS3 are genetically deleted specifically in NG2 cells, we found that deletion of STAT3 led to a reduction in oligodendrogenesis, while deletion of SOCS3 led to enhanced proliferation of NG2 cells within the glial scar after spinal cord injury. Additionally, STAT3 and SOCS3 were not required for astrogliogenesis from NG2 cells after spinal cord injury. Interestingly, genetic deletion of STAT3 and SOCS3 did not have opposing effects, suggesting that SOCS3 may have targets other than STAT3 pathway in NG2 cells after spinal cord injury. Altogether, our data show that both STAT3 and SOCS3 play important, yet unexpected, roles in NG2 cell proliferation and differentiation after spinal cord injury.

The histological assessment of spinal cord tissue in three dimensions has previously been very time consuming and prone to errors of interpretation. Advances in tissue clearing have significantly improved visualization of fluorescently labelled axons. While recent proof-of-concept studies have been performed with transgenic mice in which axons were prelabeled with GFP, investigating axonal regeneration requires stringent axonal tracing methods as well as the use of animal models in which transgenic axonal labeling is not available. Using rodent models of spinal cord injury, we labeled axon tracts of interest using both adeno-associated virus and chemical tracers and performed tetrahydrofuran-based tissue clearing to image multiple axon types in spinal cords using light sheet and confocal microscopy. Using this approach, we investigated the relationships between axons and scar-forming cells at the injury site as well as connections between sensory axons and motor pools in the spinal cord. In addition, we used these methods to trace axons in nonhuman primates. This reproducible and adaptable virus-based approach can be combined with transgenic mice or with chemical-based tract-tracing methods, providing scientists with flexibility in obtaining axonal trajectory information from transparent tissue.

IntroductionTreatment of brain arteriovenous malformations (BAVMs) is achieved by embolization, surgery, radiosurgery or any combination of these modalities. The aim of endovascular management of BAVMs before surgical resection is to minimize intraoperative blood loss, to occlude the entire BAVM or at least minimize the size of the nidus. Endovascular treatment is achieved by using n-butyl cyanoacrylate (n-BCA) or Onyx embolic agent.Methods14 Onyx and 15 n-BCA cases who were treated via endovascular procedures were randomly selected from 2003 to 2009 and were retrospectively analyzed. We began by comparing patient demographics, complication rates, Spetzler–Martin grading scale, BAVM volumes, pre- and post-embolization volumes, contrast loads, radiation times, as well as the number of feeder arteries. Volume of the nidus was calculated after three angiographic diameters of the lesion were obtained. The horizontal and vertical diameters were obtained from the anteroposterior projection and the longitudinal diameter from the lateral projection. We considered the BAVM to take an ellipsoid shape and we used Pasqualin method in calculating the volume of the BAVM: V= (wxhxl)/2ResultsThe mean pre-embolization nidal volume for Onyx and n-BCA cases were 5.59±4.84 cm3 and 4.11±4.30 cm3, respectively. No significant statistical difference between Onyx and n-BCA pre-embolization volumes was observed. The mean post-embolization volume for Onyx and n-BCA were 2.68±2.72 cm3 and 1.68±1.38 cm3, respectively. The per cent of obliteration of the BAVM was observed to be 71% in Onyx cases compared with n-BCA cases, which was 62.5% (p=0.2). Contrast load was observed to be higher in n-BCA cases compared with Onyx cases (p=0.8). However, fluoroscopy time was observed to be significantly higher in Onyx cases compared with n-BCA cases (P=0.0009). On the other hand, patients treated with Onyx as the sole embolic agent had fewer staged embolizations compared with n-BCA patients.ConclusionThe purpose of our study is to report our experience in using Onyx versus n-BCA and report our anatomic and clinical results accomplished using these two forms of treatment. Both modalities of treatment are comparable with regard to percentage of obliteration of the BAVM. However, Onyx requires a fewer number of staged embolizations to achieve the same degree of obliteration as one would achieve with n-BCA.