RT Journal Article
SR Electronic
T1 Glioma-induced alterations in neuronal activity and neurovascular coupling during disease progression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 763805
DO 10.1101/763805
A1 Mary Katherine Montgomery
A1 Sharon H. Kim
A1 Athanassios Dovas
A1 Kripa Patel
A1 Angeliki Mela
A1 Nelson Humala
A1 Hanzhi T. Zhao
A1 David N. Thibodeaux
A1 Mohammed Shaik
A1 Ying Ma
A1 Jack Grinband
A1 Daniel S. Chow
A1 Catherine Schevon
A1 Elizabeth M. C. Hillman
A1 Peter Canoll
YR 2019
UL http://biorxiv.org/content/early/2019/09/10/763805.abstract
AB 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 followed 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 in glioma-infiltrated cortex gradually decreased, while neurovascular coupling was also progressively disrupted compared to uninvolved cortex. Over time, mice developed diverse patterns of high amplitude discharges and eventually generalized seizures that begin at the infiltrative margin of the tumors. Interictal and seizure events exhibited positive neurovascular coupling in uninfiltrated cortex, however glioma-infiltrated regions exhibited inverted 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 new biomarkers and therapeutic targets.Highlights- Glioma disrupts neural synchrony between bilateral cortical regions.- WFOM reveals frequent interictal discharges and seizures during glioma progression.- Tumor development is accompanied by local changes in neurovascular coupling.- Altered neurovascular coupling drives hypoperfusion of the tumor during seizures.