Browsing by Author "Horner, Philip J."

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    Assessing Gq-GPCR–induced human astrocyte reactivity using bioengineered neural organoids
    (Rockefeller University Press, 2022) Cvetkovic, Caroline; Patel, Rajan; Shetty, Arya; Hogan, Matthew K.; Anderson, Morgan; Basu, Nupur; Aghlara-Fotovat, Samira; Ramesh, Srivathsan; Sardar, Debosmita; Veiseh, Omid; Ward, Michael E.; Deneen, Benjamin; Horner, Philip J.; Krencik, Robert; Bioengineering
    Astrocyte reactivity can directly modulate nervous system function and immune responses during disease and injury. However, the consequence of human astrocyte reactivity in response to specific contexts and within neural networks is obscure. Here, we devised a straightforward bioengineered neural organoid culture approach entailing transcription factor–driven direct differentiation of neurons and astrocytes from human pluripotent stem cells combined with genetically encoded tools for dual cell-selective activation. This strategy revealed that Gq-GPCR activation via chemogenetics in astrocytes promotes a rise in intracellular calcium followed by induction of immediate early genes and thrombospondin 1. However, astrocytes also undergo NF-κB nuclear translocation and secretion of inflammatory proteins, correlating with a decreased evoked firing rate of cocultured optogenetic neurons in suboptimal conditions, without overt neurotoxicity. Altogether, this study clarifies the intrinsic reactivity of human astrocytes in response to targeting GPCRs and delivers a bioengineered approach for organoid-based disease modeling and preclinical drug testing.
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    Assessment of spinal cord injury using ultrasound elastography in a rabbit model in vivo
    (Springer Nature, 2023) Tang, Songyuan; Weiner, Bradley; Taraballi, Francesca; Haase, Candice; Stetco, Eliana; Mehta, Shail Maharshi; Shajudeen, Peer; Hogan, Matthew; De Rosa, Enrica; Horner, Philip J.; Grande-Allen, K. Jane; Shi, Zhaoyue; Karmonik, Christof; Tasciotti, Ennio; Righetti, Raffaella; Bioengineering
    The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young’s modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.