Dynamic Evolution of the Glymphatic System at the Early Stages of Subarachnoid Hemorrhage

Hou, Changkai; Li, Jian; Wang, Bangyue; Liu, Quanlei; Zhao, Yan; Zhang, Hao; Wang, Weihan; Ren, Wen; Cui, Xiaopeng; Yang, Xinyu

doi:10.3389/fneur.2022.924080

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…The impact of the glymphatic system has also been studied in relation to SAH. An overview of the 13 studies can be found in Supplemental Table 1 , which includes 11 animal studies, 1 study with human participants, and 1 study with both human and animal subjects [ 21 – 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…In mice, decreased fluorescent tracer penetration and enlarged PVS, along with an increase in P-tau (phosphorylated tau) and tau-protein presence, decreased neurological scoring, and AQP4 depolarization, were observed after SAH, indicating glymphatic dysfunction [ 21 , 23 ]. Deletion of the AQP4 gene in mice and rats has also been observed to aggravate glymphatic dysfunction, neuronal damage, and neurological deficits following SAH [ 24 , 33 ].…”

Section: Resultsmentioning

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%

The glymphatic system for neurosurgeons: a scoping review

Al Masri,

Corell,

Michaëlsson

et al. 2024

Neurosurg Rev

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“…Recent stroke research analyzing AQP4 has just begun to focus on the periinfarct cortex 12 , 36 . As indicated in Figure 3 A-B , analysis of the AQP4 polarity in the periinfarct cortex revealed a decreased AQP4 polarity at 1, 7, and 21 dpi when compared to non-ischemic sham mice.…”

Section: Resultsmentioning

confidence: 99%

Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation

Xin¹,

Pan²,

Wei³

et al. 2023

Theranostics

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Background: Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow. Methods: Primary microglia and astrocytes were exposed to oxygen-glucose deprivation (OGD) injury. For analyzing the role of AQP4 expression patterns under hypoxic conditions, a co-culture model of astrocytes and microglia was established. Further studies applied a stroke model, where some mice also received an intracisternal tracer infusion of rhodamine B. As such, these in vivo studies involved the analysis of AQP4 polarization, CSF flow, astrogliosis, and neuroinflammation as well as ischemia-induced brain injury. Results: Preconditioned EVs decreased periinfarct AQP4 depolarization, brain edema, astrogliosis, and inflammation in stroke mice. Likewise, EVs promoted postischemic CSF flow and cerebral blood perfusion, and neurological recovery. Under in vitro conditions, hypoxia stimulated M2 microglia polarization, whereas EVs augmented M2 microglia polarization and repressed M1 microglia polarization even further. In line with this, astrocytes displayed upregulated AQP4 clustering and proinflammatory cytokine levels when exposed to OGD, which was reversed by preconditioned EVs. Reduced AQP4 depolarization due to EVs, however, was not a consequence of unspecific inflammatory regulation, since LPS-induced inflammation in co-culture models of astrocytes and microglia did not result in altered AQP4 expression patterns in astrocytes. Conclusions: These findings show that hypoxic microglia may participate in protecting against stroke-induced brain damage by regulating poststroke inflammation, astrogliosis, AQP4 depolarization, and CSF flow due to EV release.

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“…This may be related to the GS concept introduced in 2012 [3]. Some studies have predicted that the GS in cognition will continue to gain strong attention in the future [25].…”

Section: Development Of Gs In Cognitionmentioning

confidence: 93%

A bibliometric analysis of the glymphatic system in cognition from 2009 to 2023

Ying,

Xu,

et al. 2024

Preprint

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Background: Since the discovery of the glymphatic system in mice with clearance functions distributed throughout the brain, more and more scholars have begun to study the glymphatic system. However, there are a limited number of correlations between glymphatic system and cognition. Therefore, this study aimed to evaluate the research trends, hotspots, and frontiers of glymphatic system in cognition using bibliometric analysis. Methods: Publications from the Web of Science Core Collection (WoSCC) database spanning 15 years from 1 January 2009 to 31 December 2023 were screened. All eligible publication were included based on our comprehensive search strategy. The analysis of annual publications, countries/regions, institutions, journals, authors, co-cited journals, co-cited authors, and keywords was conducted using CiteSpace and VOSviewer, and the hotspots and major ﬁndings of the glymphatic system in cognition were summarised. In addition, ArcGIS software was used to geovisualize the count of publications. Results: A total of 625 publications were included in this study. Overall, the number of publications has been increasing steadily per year. These publications were published in 59 countries/regions and 149 institutions. Of these, American institutions had the highest number of publications, and their international inﬂuence also ranked first. The journal “Neurology” published the most publications and was considered the most co-cited journal. Wardlaw, Joanna M was the author of the most published articles and the most cited authors. The article entitled “The glymphatic pathway in neurological disorders” published in Lancet neurology had the most citations. The keywords with the highest number of occurrences were “Alzheimer disease” and “small vessel disease”, which were regarded as research hotspots. Three main clusters were shown in the keywords clustering network. Alzheimer's disease and perivascular spaces had been a hot topic for a long time and from 2017 research on GS increased. Among 19 emergent terms, “Virchow robin spaces”, “vascular dementia”, and “autosomal dominant arteriopathy” were the ﬁrst, and “white matter lesions” were the strongest. Conclusion: Previous research has focused mainly on perivascular spaces, however, with the concept of the glymphatic system was introduced, the correlation of the glymphatic system in cognition have gradually increased. Currently, limited studies have been conducted on the glymphatic system in cognition , and we hope that this study will provide the recommendation for the future research.

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Dynamic Evolution of the Glymphatic System at the Early Stages of Subarachnoid Hemorrhage

Cited by 8 publications

References 45 publications

The glymphatic system for neurosurgeons: a scoping review

The glymphatic system for neurosurgeons: a scoping review

Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation

A bibliometric analysis of the glymphatic system in cognition from 2009 to 2023

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