Biology subjects

Connolly, E. S.

Publications and source records attributed to Connolly, E. S..

3 recordsLinked to original sources

bioRxiv2026

A Fully Endovascular Neural Interface

Electrical stimulation of neural circuits is expanding therapeutic strategies to modulate brain, autonomic, and immune functions. Devices delivered endovascularly offer a less invasive alternative to conventional implanted electrodes, while delivering spatio-temporal specificity superior to noninvasive techniques. We demonstrate a fully endovascular sub-1-mm3 implant, utilizing ultrasound for wireless power delivery and data telemetry in a fashion invariant to device orientation. The implant consists of piezoelectric transducers, an energy storage capacitor, an application-specific integrated circuit, and electrodes packaged on a 7-{micro}m-thick polyimide scaffold. The implant can be delivered through a microcatheter in a manner analogous to conventional neurovascular stents, and self-expands upon deployment to appose the vessel walls. We demonstrate intravascular stimulation of the autonomic nervous system from the carotid artery, achieving modulation of blood pressure in rabbits. This approach establishes a broadly applicable platform for neural interfaces enabling both stimulation and recording.

neuroscience↗

bioRxiv2024

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes

ObjectivesAlthough lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. MethodsICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE ([≥]33% and/or [≥]6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed. ResultsAmong 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice. ConclusionsThese results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

pathology↗

bioRxiv2023

Atherosclerosis is a smooth muscle cell-driven tumor-like disease

Atherosclerosis, the leading cause of cardiovascular disease, is a chronic inflammatory disease involving pathological activation of multiple cell types, such as immunocytes (e.g., macrophage, T cells), smooth muscle cells (SMCs), and endothelial cells. Multiple lines of evidence have suggested that SMC "phenotypic switching" plays a central role in atherosclerosis development and complications. Yet, SMC roles and mechanisms underlying the disease pathogenesis are poorly understood. Here, employing SMC lineage tracing mice, comprehensive molecular, cellular, histological, and computational profiling, coupled to genetic and pharmacological studies, we reveal that atherosclerosis, in terms of SMC behaviors, share extensive commonalities with tumors. SMC-derived cells in the disease show multiple characteristics of tumor cell biology, including genomic instability, replicative immortality, malignant proliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. SMC-specific expression of oncogenic KrasG12D accelerates SMC phenotypic switching and exacerbates atherosclerosis. Moreover, we present a proof of concept showing that niraparib, an anti-cancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. Our work provides systematic evidence that atherosclerosis is a tumor-like disease, deepening the understanding of its pathogenesis and opening prospects for novel precision molecular strategies to prevent and treat atherosclerotic cardiovascular disease.

cell biology↗