Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate

Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, M; Pasquet, Nolwenn; Gakuba, Clément; Emery, Évelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

doi:10.1161/strokeaha.117.017014

Cited by 123 publications

(128 citation statements)

References 11 publications

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“…Since the initial description of glymphatic exchange of CSF and ISF along perivascular spaces (1), several additional related studies have been published (22)(23)(24). In light of this increased understanding of fluid movement in the brain, it is critical that we assess how these data fit with the glymphatic hypothesis as it was initially proposed and thus identify elements of the hypothesis that require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-4 dependent glymphatic solute transport in rodent brain

Mestre

Kress

Zou

et al. 2017

Preprint

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The glymphatic system is a brain-wide metabolite clearance pathway, impairment of which in post-traumatic and ischemic brain or healthy aging is proposed to contribute to intracerebral accumulation of amyloid-β and tau proteins. Glymphatic perivascular influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent publication that failed to find an effect of Aqp4 knockout on perivascular CSF tracer influx and interstitial fluid (ISF) tracer dispersion, four independent research groups have herein re-examined the importance of Aqp4 in glymphatic fluid transport. We concur in finding that CSF tracer influx, as well as fluorescently-tagged amyloid-β efflux, are significantly faster in wild-type mice than in three different transgenic lines featuring disruption of the Aqp4 gene and one line in which AQP4 expression lacks the critical perivascular localization (Snta1 knockout). These data validate the role of AQP4 in supporting fluid and solute transport and efflux in brain in accordance with the glymphatic system model.

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Section: Discussionmentioning

confidence: 99%

Aquaporin-4 dependent glymphatic solute transport in rodent brain

Mestre

Kress

Zou

et al. 2017

Preprint

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“…In 2015 and 2016, two studies also demonstrated the existence of true cerebral lymphatic vessels in the dura [13,71], which may support the glymphatic system's functions. Although the majority of studies of the glymphatic system have so far been done in rodents, there is evidence of the existence of a similar cerebral lymphatic system in the non-human primate [18] and the human brains [16,87,88].…”

Section: Aβ Clearance Through the Glymphatic Systemmentioning

confidence: 99%

“…The glymphatic system may play an important role in the transport of nutrients, such as glucose, from the blood to brain tissue [73], which can be impaired during physiological aging [14] and AD [15]. By calculating the MRI-detected contrast enhancement ratio between the olfactory bulbs and the cerebellum of mice after contrast agent injection in the cisterna magna, Gaberel and colleagues have observed that the glymphatic system is impaired after ischemic stroke (signal intensity ratio: 1.0 in controls vs. 0.7 after stroke, p < 0.05) and after subarachnoid hemorrhage (signal intensity ratio: 1.3 in controls vs. 0.5 after subarachnoid hemorrhage, p < 0.05) [17,18]. Up to 40% of glymphatic system impairment may develop during aging, accompanied by a 27% reduction in the vessel wall pulsatility of intracortical arterioles, and widespread loss of AQP4 polarization along the penetrating arteries, which could contribute to Aβ deposition [14].…”

Section: Aβ Clearance Through the Glymphatic Systemmentioning

confidence: 99%

“…Post-stroke loss of BBB integrity influences perivascular space integrity and glymphatic system efficiency [17,18,138]. Several studies, in animal models as well as in patients, have shown that impaired CSF and glymphatic clearance could contribute to accumulation and aggregation of waste products and other compounds in the CSF and brain parenchyma [139].…”

Section: Glymphatic System Impairmentmentioning

confidence: 99%

“…For example, Aβ drainage via the cerebral perivascular space has been found to be impaired with aging leading to increase in Aβ deposits in an AD mouse model [14][15][16]. Furthermore, it has been reported that this perivascular pathway is impaired after both hemorrhagic and ischemic stroke, as observed in rodents and non-human primates [17,18]. Abnormal perivascular space integrity, potentially correlated with malfunction of the glymphatic system and Aβ drainage, could therefore be considered as a possible mechanism explaining the link between CAA, stroke, and dementia [6,16,19].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

Goulay

Romo

Hol

et al. 2019

Transl. Stroke Res.

Self Cite

100

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Stroke and Alzheimer's disease (AD) are cerebral pathologies with high socioeconomic impact that can occur together and mutually interact. Vascular factors predisposing to cerebrovascular disease have also been specifically associated with development of AD, and acute stroke is known to increase the risk to develop dementia. Despite the apparent association, it remains unknown how acute cerebrovascular disease and development of AD are precisely linked and act on each other. It has been suggested that this interaction is strongly related to vascular deposition of amyloid-β (Aβ), i.e., cerebral amyloid angiopathy (CAA). Furthermore, the blood-brain barrier (BBB), perivascular space, and the glymphatic system, the latter proposedly responsible for the drainage of solutes from the brain parenchyma, may represent key pathophysiological pathways linking stroke, Aβ deposition, and dementia. In this review, we propose a hypothetic connection between CAA, stroke, perivascular space integrity, and dementia. Based on relevant pre-clinical research and a few clinical case reports, we speculate that impaired perivascular space integrity, inflammation, hypoxia, and BBB breakdown after stroke can lead to accelerated deposition of Aβ within brain parenchyma and cerebral vessel walls or exacerbation of CAA. The deposition of Aβ in the parenchyma would then be the initiating event leading to synaptic dysfunction, inducing cognitive decline and dementia. Maintaining the clearance of Aβ after stroke could offer a new therapeutic approach to prevent post-stroke cognitive impairment and development into dementia.

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Very Low‐Intensity Ultrasound Facilitates Glymphatic Influx and Clearance via Modulation of the TRPV4‐AQP4 Pathway

Wu,

Liao,

Chu

et al. 2024

Advanced Science

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Recently, the glymphatic system has been proposed as a mechanism for waste clearance from the brain parenchyma. Glymphatic dysfunction has previously been shown to be associated with several neurological diseases, including Alzheimer's disease, traumatic brain injury, and stroke. As such, it may serve as an important target for therapeutic interventions. In the present study, very low‐intensity ultrasound (VLIUS) (center frequency, 1 MHz; pulse repetition frequency, 1 kHz; duty factor, 1%; spatial peak temporal average intensity [Ispta] = 3.68 mW cm2; and duration, 5 min) is found to significantly enhance the influx of cerebrospinal fluid tracers into the paravascular spaces of the brain, and further facilitate interstitial substance clearance from the brain parenchyma, including exogenous β‐amyloid. Notably, no evidence of brain damage is observed following VLIUS stimulation. VLIUS may enhance glymphatic influx via the transient receptor potential vanilloid‐4‐aquaporin‐4 pathway in astrocytes. This mechanism may provide insights into VLIUS‐regulated glymphatic function that modifies the natural course of central nervous system disorders related to waste clearance dysfunction.

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Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate

Abstract: The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH.

Cited by 123 publications

References 11 publications

Aquaporin-4 dependent glymphatic solute transport in rodent brain

Aquaporin-4 dependent glymphatic solute transport in rodent brain

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

Very Low‐Intensity Ultrasound Facilitates Glymphatic Influx and Clearance via Modulation of the TRPV4‐AQP4 Pathway

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