Woven Endobridge embolization: Indications and innovation.

The treatment of intracranial aneurysms has seen incredible advancements over the last few decades. Long-term occlusion of wide-neck bifurcation aneurysms remains technically challenging. The Woven Endobridge (WEB) embolization device is innovative in its construction and uses. The design of the device has evolved over the last decade. Pre-clinical and clinical trials are ongoing and continue to inform the development of intrasaccular flow-diverting devices. The WEB device is currently approved by the U.S. Food and Drug Administration (FDA) for treating wide-neck aneurysms. The safety and efficacy of the WEB device have yielded promising clinical results that may have additional indications. This review aims to discuss the development of the WEB device and the current state of the WEB device in the treatment of wide-neck aneurysms. We also summarize ongoing clinical studies and potential innovative uses.

Complementary Medicine and Expressive Arts Therapy: Adjuvant for Recovery Following Neurosurgical Procedures.

Art as a way of healing is primordial in many cultures. Expressive Arts Therapy (ExAT) uses art, music, dance, and writing to help individuals navigate their healing journey. Patient self-expression as a mode of recovery has been observed in patients with Parkinson's disease, epilepsy, Amyotrophic Lateral Sclerosis (ALS) and cancer. Complementary medical approaches such as acupuncture and mindfulness have also demonstrated benefits in patients suffering from neurological injury. Complementary medicine and ExAT are not mainstream approaches following neurosurgical procedures. There are very few systematic studies evaluating the benefits of expressive arts in neurosurgery. Advances in telemedicine and mobile applications may facilitate the incorporation of complementary medicine and ExAT into patient recovery. The purpose of our study is to explore the use of complementary medicine and ExAT in neurosurgical recovery. We start with a brief introduction of ExAT followed by available treatments offered. We discuss the benefits of multidisciplinary care and emerging technologies and how they can facilitate incorporation of complementary medicine and ExAT in neurosurgery. Finally, we review several clinical studies that have demonstrated success in using complementary medicine. Our goal is to provide alternative approaches to neurosurgery recovery so that patients may receive with the best care possible.

Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK.

Cell migration within 3D interstitial microenvironments is sensitive to extracellular matrix (ECM) properties, but the mechanisms that regulate migration guidance by 3D matrix features remain unclear. To examine the mechanisms underlying the cell migration response to aligned ECM, which is prevalent at the tumor-stroma interface, we utilized time-lapse microscopy to compare the behavior of MDA-MB-231 breast adenocarcinoma cells within randomly organized and well-aligned 3D collagen ECM. We developed a novel experimental system in which cellular morphodynamics during initial 3D cell spreading served as a reductionist model for the complex process of matrix-directed 3D cell migration. Using this approach, we found that ECM alignment induced spatial anisotropy of cells' matrix probing by promoting protrusion frequency, persistence, and lengthening along the alignment axis and suppressing protrusion dynamics orthogonal to alignment. Preference for on-axis behaviors was dependent upon FAK and Rac1 signaling and translated across length and time scales such that cells within aligned ECM exhibited accelerated elongation, front-rear polarization, and migration relative to cells in random ECM. Together, these findings indicate that adhesive and protrusive signaling allow cells to respond to coordinated physical cues in the ECM, promoting migration efficiency and cell migration guidance by 3D matrix structure.

Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks.

Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.

Mechanisms of antagonism of the GluR2 AMPA receptor: structure and dynamics of the complex of two willardiine antagonists with the glutamate binding domain.

Ionotropic glutamate receptors mediate the majority of vertebrate excitatory synaptic transmission. The development of selective antagonists for glutamate receptor subtypes is of interest in the treatment of a variety of neurological disorders. This study presents the crystal structure of the binding domain of GluR2 bound to two antagonists (UBP277 and UBP282) that are derivatives of the natural product, willardiine. The antagonists bind to one lobe of the protein with interactions similar to agonists. Interaction with the second lobe differs between the two antagonists, resulting in a different position of the uracil ring and different orientations of the bilobed structure. UBP277 binding produces a stable lobe orientation that is similar to the apo state, but the binding of UBP282 produces the largest hyperextension of the lobes yet reported for an AMPA receptor. The carboxyethyl (UBP277) and carboxybenzyl (UBP282) substituents in the N(3) position keep the lobes separated by a "foot-in-the-door" mechanism and the internal dynamics are minimal compared to the CNQX-bound form of the protein (which makes minimal contacts with one of the two lobes). In contrast to the antagonists CNQX and DNQX, UBP277 and UBP282 produce complexes with higher thermal stability, but affinities that are more than 100-fold lower. These structures support the idea that antagonism is associated with the overall orientation of the lobes rather than with specific interactions, and antagonism can rise either from specific interactions with both lobes ("foot-in-the-door" mechanism) or from the lack of extensive interactions with one of the two lobes.