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Publication : Glioma-Induced Alterations in Neuronal Activity and Neurovascular Coupling during Disease Progression.

First Author  Montgomery MK Year  2020
Journal  Cell Rep Volume  31
Issue  2 Pages  107500
PubMed ID  32294436 Mgi Jnum  J:299207
Mgi Id  MGI:6488847 Doi  10.1016/j.celrep.2020.03.064
Citation  Montgomery MK, et al. (2020) Glioma-Induced Alterations in Neuronal Activity and Neurovascular Coupling during Disease Progression. Cell Rep 31(2):107500
abstractText  Diffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption, and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms and causal relationships to disease progression are poorly characterized. Here, we follow glioma progression in awake Thy1-GCaMP6f mice using in vivo wide-field optical mapping to monitor alterations in both neuronal activity and functional hemodynamics. The bilateral synchrony of spontaneous neuronal activity gradually decreases in glioma-infiltrated cortical regions, while neurovascular coupling becomes progressively disrupted compared to uninvolved cortex. Over time, mice develop diverse patterns of high amplitude discharges and eventually generalized seizures that appear to originate at the tumors' infiltrative margins. Interictal and seizure events exhibit positive neurovascular coupling in uninfiltrated cortex; however, glioma-infiltrated regions exhibit disrupted hemodynamic responses driving seizure-evoked hypoxia. These results reveal a landscape of complex physiological interactions occurring during glioma progression and present new opportunities for exploring novel biomarkers and therapeutic targets.
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