Danielle Edwards

The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) protocol: novel method for evaluating human stroke

Background Ischemic stroke research faces difficulties in translating pathology between animal models and human patients to develop treatments. Mechanical thrombectomy, for the first time, offers a momentary window into the changes occurring in ischemia. We developed a tissue banking protocol to capture intracranial thrombi and the blood immediately proximal and distal to it. Objective To develop and share a reproducible protocol to bank these specimens for future analysis. Methods We established a protocol approved by the institutional review board for tissue processing during thrombectomy (www.clinicaltrials.gov NCT03153683). The protocol was a joint clinical/basic science effort among multiple laboratories and the NeuroInterventional Radiology service line. We constructed a workspace in the angiography suite, and developed a step-by-step process for specimen retrieval and processing. Results Our protocol successfully yielded samples for analysis in all but one case. In our preliminary dataset, the process produced adequate amounts of tissue from distal blood, proximal blood, and thrombi for gene expression and proteomics analyses. We describe the tissue banking protocol, and highlight training protocols and mechanics of on-call research staffing. In addition, preliminary integrity analyses demonstrated high-quality yields for RNA and protein. Conclusions We have developed a novel tissue banking protocol using mechanical thrombectomy to capture thrombus along with arterial blood proximal and distal to it. The protocol provides high-quality specimens, facilitating analysis of the initial molecular response to ischemic stroke in the human condition for the first time. This approach will permit reverse translation to animal models for treatment development.

Edema and BBB Breakdown in Stroke

Abstract Stroke is a leading cause of death and disability affecting 15 million people worldwide. Although rapid recognition and treatment have dropped mortality rates, many are left with permanent disability. Approximately 87% of all strokes result from the occlusion of cerebrovasculature (ischemic strokes). Current research distinguishes between zones of core infarct and areas of metabolically compromised but potentially viable tissue receiving collateral circulation known as penumbra. Research has long focused on how endogenous mechanisms of neuroprotection and neurorepair affect penumbral expansion. Such therapeutic approaches have included antiinflammatory interventions, reactive oxygen species scavengers, and many other targets with the common goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. This chapter will discuss acute and chronic molecular mechanisms underlying edema following ischemic stroke.

Understanding nanomaterial synthesis with in situ transmission electron microscopy

The vapor-liquid-solid (VLS) nanowire growth technique is a synthesis method widely used to grow high-quality, single-crystalline semiconductor nanowires [1-3]. First introduced in 1964 by Wagner and Ellis to grow silicon nanowires, this method has evolved to utilize many different metal catalyst materials to grow a wide variety of inorganic nanowires with facile control of diameter, length, and dopant concentration [1,4]. These inorganic nanowires have many applications, such as for Li-ion battery electrodes, gas sensors, and solar cell components [5-7]. While VLS is a ubiquitous growth method, understanding of the growth kinetics is limited, especially for binary and ternary crystal systems. Theoretical predictions suggest that the growth of such nanowires is governed by steady-state kinetics, and that the crystal chemistry of the reverse process may be different from that which governs the nanowire growth [8]. The use of in situ techniques has advanced the understanding of the VLS process and the kinetics of VLS growth [9]. By use of heating in a transmission electron microscope (TEM), we have developed a method to observe the Au-catalyzed VLS growth of metal oxide nanowires occurring in reverse; this nanowire dissolution is dubbed the solid-liquid-vapor (SLV) process.