Local Glioma Cells Are Associated with Vascular Dysregulation

Bowden, Stephen; Gill, Brian J A; Englander, Zachary; Horenstein, C.I.; Zanazzi, George; Chang, Peter D.; Samanamud, Jorge; Lignelli, Angela; Bruce, Jeffrey N.; Canoll, Peter; Grinband, Jack

doi:10.3174/ajnr.a5526

Cited by 18 publications

(14 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In regard to resting-state fMRI, our results suggest that both neuronal desynchronization and neurovascular disruption could contribute to apparent changes in fMRI-based measures of “functional connectivity” related to tumor progression ( Dierker et al, 2017 ; Hadjiabadi et al, 2018 ). Nevertheless, these results do suggest a firm physiological basis for studies that have noted the ability of resting state fMRI data to delineate glioma tumor boundaries ( Agarwal et al, 2016 ; Bowden et al, 2018 ; Chow et al, 2016 ).…”

Section: Discussionmentioning

confidence: 73%

“…Tumor-dependent alterations in neurovascular coupling could lead to misinterpretation of fMRI data, and errors in the localization of functional boundaries. Several recent human resting-state fMRI studies have also shown that gliomas can cause focal changes in the BOLD signals detected in the tumor and surrounding infiltrated cortex, characterized by a loss of synchrony between the tumor and the contralateral hemisphere ( Agarwal et al, 2016 ; Bowden et al, 2018 ; Chow et al, 2016 ). Although these studies could not disambiguate whether changes in BOLD were caused by altered neuronal activity, neurovascular coupling, or both, they suggest that vascular signals could be helpful biomarkers of tumor progression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

View full text Add to dashboard Cite

SUMMARY 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.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The slides were then scanned and digitized at 40x magnification on a Leica SCN400 system (Leica Biosystems). Total cell density and SOX2 + nuclei were measured using a semi-automated cell-counting algorithm as previously described (49). Algorithm-derived cell counts were manually verified, and total cell density and SOX2 cell density were assessed for one representative high-power field from each sample.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma

Yuan

Levitin

Frattini

et al. 2018

Preprint

View full text Add to dashboard Cite

Despite extensive molecular characterization, we lack a comprehensive picture of lineage identity, differentiation, and microenvironmental composition in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq. While HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, implying a molecular interaction between glioma and immune cells. Finally, we found that myeloid cells are highly diverse in HGG with high expression of pro-inflammatory cytokines and microglial markers on one extreme to a macrophage-like phenotype on the other. However, enrichment of either gene signature is predictive of poor survival. Statement of SignificanceWe used large-scale single-cell RNA-Seq to establish the extent of neural and non-neural lineage diversity in high-grade gliomas, discovery a tight coupling between proliferation and cell type, and identify disparate myeloid phenotypes that are predictive of poor survival.

show abstract

“…In regards to resting-state fMRI, our results suggest that both neuronal desynchronization and neurovascular disruption could contribute to apparent changes in fMRI-based measures of 'functional connectivity' related to tumor progression (Hadjiabadi et al, 2018) (Dierker et al, 2017). Nevertheless, these results do suggest a firm physiological basis for studies which have noted the ability of resting state fMRI data to delineate glioma tumor boundaries (Bowden et al, 2018) (Chow et al, 2016) (Agarwal et al, 2016).…”

Section: Progressive Disruption Of Neurovascular Couplingmentioning

confidence: 66%

“…Tumor-dependent alterations in neurovascular coupling could lead to misinterpretation of fMRI data, and errors in the localization of functional boundaries. Several recent human resting-state fMRI studies have also shown that gliomas can cause focal changes in the blood oxygen level dependent (BOLD) signals in the tumor and surrounding infiltrated cortex, characterized by a loss of synchrony between the tumor and the contralateral hemisphere (Bowden et al, 2018) (Chow et al, 2016) (Agarwal et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Glioma-induced alterations in neuronal activity and neurovascular coupling during disease progression

Montgomery

Kim

Dovas

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractDiffusely 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.

show abstract

Local Glioma Cells Are Associated with Vascular Dysregulation

Cited by 18 publications

References 41 publications

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

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

Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma

Glioma-induced alterations in neuronal activity and neurovascular coupling during disease progression

Contact Info

Product

Resources

About