Glymphatic transport is reduced in rats with spontaneous pituitary tumor

Li, Lian; Ding, Guangliang; Zhang, Li; Luo, Haiyan; Davoodi‐Bojd, Esmaeil; Li, Qingjiang; Chopp, Michael; Zhang, Zheng Gang; Jiang, Quan

doi:10.3389/fmed.2023.1189614

Cited by 3 publications

(5 citation statements)

References 90 publications

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“… Decrease in glymphatic function may be linked to the formation of PTBE. Li et al [ 52 ] Rats with spontaneous pituitary tumor Rat 22–24 months n = 14 Intracisternal contrast injection, evaluated with MRI T2-weighted and dynamic 3D T1-weighted. A lower incidence of enhancement of glymphatic influx nodes and pituitary and pineal recesses in rats with pituitary tumors.…”

Section: Resultsmentioning

confidence: 99%

“…This provides evidence for the role of glymphatic dysfunction in the formation of PTBE [ 50 , 51 ]. The glymphatic system also seems to be affected in rat model with spontaneous pituitary tumor, which could result in cognitive impairment [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

“…The link between brain tumors and the glymphatic system has been explored in six studies, as detailed in Table 3 [47][48][49][50][51][52]. Of these, three studies were conducted on human subjects and three involved animal models.…”

Section: Intracranial Tumorsmentioning

confidence: 99%

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The glymphatic system for neurosurgeons: a scoping review

Al Masri,

Corell,

Michaëlsson

et al. 2024

Neurosurg Rev

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The discovery of the glymphatic system has revolutionized our understanding of cerebrospinal fluid (CSF) circulation and interstitial waste clearance in the brain. This scoping review aims to synthesize the current literature on the glymphatic system’s role in neurosurgical conditions and its potential as a therapeutic target. We conducted a comprehensive search in PubMed and Scopus databases for studies published between January 1, 2012, and October 31, 2023. Studies were selected based on their relevance to neurosurgical conditions and glymphatic function, with both animal and human studies included. Data extraction focused on the methods for quantifying glymphatic function and the main results. A total of 67 articles were included, covering conditions such as idiopathic normal pressure hydrocephalus (iNPH), idiopathic intracranial hypertension (IIH), subarachnoid hemorrhage (SAH), stroke, intracranial tumors, and traumatic brain injury (TBI). Significant glymphatic dysregulation was noted in iNPH and IIH, with evidence of impaired CSF dynamics and delayed clearance. SAH studies indicated glymphatic dysfunction with the potential therapeutic effects of nimodipine and tissue plasminogen activator. In stroke, alterations in glymphatic activity correlated with the extent of edema and neurological recovery. TBI studies highlighted the role of the glymphatic system in post-injury cognitive outcomes. Results indicate that the regulation of aquaporin-4 (AQP4) channels is a critical target for therapeutic intervention. The glymphatic system plays a critical role in the pathophysiology of various neurosurgical conditions, influencing brain edema and CSF dynamics. Targeting the regulation of AQP4 channels presents as a significant therapeutic strategy. Although promising, the translation of these findings into clinical practice requires further human studies. Future research should focus on establishing non-invasive biomarkers for glymphatic function and exploring the long-term effects of glymphatic dysfunction.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The glymphatic system for neurosurgeons: a scoping review

Al Masri,

Corell,

Michaëlsson

et al. 2024

Neurosurg Rev

View full text Add to dashboard Cite

show abstract

“…While studies to understand the significance of these networks in maintaining brain health and function are ongoing [9,10], there is limited knowledge regarding glymphatic function in the presence of a brain tumor. In addition to biochemical effects from cancer cells, tumor-induced mechanical forces may damage the brain [11] and severely impact waste clearance in brain tumor patients [12][13][14][15][16][17][18]. However, the mechanisms of this effect have yet to be fully elucidated [2].…”

Section: Introductionmentioning

confidence: 99%

“…This is best illustrated by the edema that results from brain tumors, which is associated with worse prognosis and decreased glymphatic function [13,18]. In vivo studies of a range of brain tumor types consistently demonstrate reduced rates of tracer influx and outflux, with a net lower rate of clearance and increased residual tracer [12][13][14][16][17][18]. This may be mediated in part by decreased AQP4 expression in perivascular astrocytes and heavily disrupted vasculature associated with brain tumors [14,24,33,34].…”

Section: Introductionmentioning

confidence: 99%

Simulating the Impact of Tumor Mechanical Forces on Glymphatic Networks in the Brain Parenchyma

Siri,

Burchett,

Datta

2024

Preprint

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Background: The brain glymphatic system is currently being explored in the context of many neurological disorders and diseases, including traumatic brain injury, Alzheimer's disease, and ischemic stroke. However, little is known about the impact of brain tumors on glymphatic function. Mechanical forces generated during tumor development and growth may be responsible for compromised glymphatic transport pathways, reducing waste clearance and cerebrospinal fluid (CSF) transport in the brain parenchyma. One such force is solid stress, i.e., growth-induced forces from cell hyperproliferation and excess matrix deposition. Because there are no prior studies assessing the impact of tumor-derived solid stress on glymphatic system structure and performance in the brain parenchyma, this study serves to fill an important gap in the field. Methods: We adapted a previously developed Electrical Analog Model using MATLAB Simulink for glymphatic transport coupled with Finite Element Analysis for tumor mechanical stresses and strains in COMSOL. This allowed simulation of the impact of tumor mechanical force generation on fluid transport within brain parenchymal glymphatic units, which include paravascular spaces, astrocytic networks, interstitial spaces, and capillary basement membranes. We conducted a parametric analysis to compare the contributions of tumor size, tumor proximity, and ratio of glymphatic subunits to the stress and strain experienced by the glymphatic unit and corresponding reduction in flow rate of CSF. Results:. Mechanical stresses intensify with proximity to the tumor and increasing tumor size, highlighting the vulnerability of nearby glymphatic units to tumor-derived forces. Our stress and strain profiles reveal compressive deformation of these surrounding glymphatics and demonstrate that varying the relative contributions of astrocytes vs. interstitial spaces impact the resulting glymphatic structure significantly under tumor mechanical forces. Increased tumor size and proximity caused increased stress and strain across all glymphatic subunits, as does decreased astrocyte composition. Indeed, our model reveals an inverse correlation between extent of astrocyte contribution to the composition of the glymphatic unit and the resulting mechanical stress. This increased mechanical strain across the glymphatic unit decreases the venous efflux rate of CSF, dependent on the degree of strain and the specific glymphatic subunit of interest. For example, a 20% mechanical strain on capillary basement membranes does not significantly decrease venous efflux (2% decrease in flow rates), while the same magnitude of strain on astrocyte networks and interstitial spaces decreases efflux flow rates by 7% and 22%, respectively. Conclusion: Our simulations reveal that solid stress from brain tumors directly reduces glymphatic fluid transport, independently from biochemical effects from cancer cells. Understanding these pathophysiological implications is crucial for developing targeted interventions aimed at restoring effective waste clearance mechanisms in the brain. This study opens potential avenues for future experimental research in brain tumor-related glymphatic dysfunction.

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Simulating the impact of tumor mechanical forces on glymphatic networks in the brain parenchyma

Siri,

Burchett,

Datta

2024

Biomech Model Mechanobiol

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The brain glymphatic system is currently being explored in the context of many neurological disorders and diseases, including traumatic brain injury, Alzheimer’s disease, and ischemic stroke. However, little is known about the impact of brain tumors on glymphatic function. Mechanical forces generated during tumor development and growth may be responsible for compromised glymphatic transport pathways, reducing waste clearance and cerebrospinal fluid (CSF) transport in the brain parenchyma. One such force is solid stress, i.e., growth-induced forces from cell hyperproliferation and excess matrix deposition. Because there are no prior studies assessing the impact of tumor-derived solid stress on glymphatic system structure and performance in the brain parenchyma, this study serves to fill an important gap in the field. We adapted a previously developed Electrical Analog Model using MATLAB Simulink for glymphatic transport coupled with Finite Element Analysis for tumor mechanical stresses and strains in COMSOL. This allowed simulation of the impact of tumor mechanical force generation on fluid transport within brain parenchymal glymphatic units—which include perivascular spaces, astrocytic networks, interstitial spaces, and capillary basement membranes. We conducted a parametric analysis to compare the contributions of tumor size, tumor proximity, and ratio of glymphatic subunits to the stress and strain experienced by the glymphatic unit and corresponding reduction in flow rate of CSF. Mechanical stresses intensify with proximity to the tumor and increasing tumor size, highlighting the vulnerability of nearby glymphatic units to tumor-derived forces. Our stress and strain profiles reveal compressive deformation of these surrounding glymphatics and demonstrate that varying the relative contributions of astrocytes vs. interstitial spaces impact the resulting glymphatic structure significantly under tumor mechanical forces. Increased tumor size and proximity caused increased stress and strain across all glymphatic subunits, as does decreased astrocyte composition. Indeed, our model reveals an inverse correlation between extent of astrocyte contribution to the composition of the glymphatic unit and the resulting mechanical stress. This increased mechanical strain across the glymphatic unit decreases the venous efflux rate of CSF, dependent on the degree of strain and the specific glymphatic subunit of interest. For example, a 20% mechanical strain on capillary basement membranes does not significantly decrease venous efflux (2% decrease in flow rates), while the same magnitude of strain on astrocyte networks and interstitial spaces decreases efflux flow rates by 7% and 22%, respectively. Our simulations reveal that solid stress from growing brain tumors directly reduces glymphatic fluid transport, independently from biochemical effects from cancer cells. Understanding these pathophysiological implications is crucial for developing targeted interventions aimed at restoring effective waste clearance mechanisms in the brain. This study opens potential avenues for future experimental research in brain tumor-related glymphatic dysfunction.

show abstract

Glymphatic transport is reduced in rats with spontaneous pituitary tumor

Cited by 3 publications

References 90 publications

The glymphatic system for neurosurgeons: a scoping review

The glymphatic system for neurosurgeons: a scoping review

Simulating the Impact of Tumor Mechanical Forces on Glymphatic Networks in the Brain Parenchyma

Simulating the impact of tumor mechanical forces on glymphatic networks in the brain parenchyma

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