Impaired glymphatic system in secondary degeneration areas after ischemic stroke in rats

Lin, Lixing; Hao, Xiang; Li, Chanchan; Sun, Congjian; Wang, Xiaohong; Yin, Lina; Zhang, Xiaoxue; Tian, Jiaqi; Yang, Yanmei

doi:10.1016/j.jstrokecerebrovasdis.2020.104828

Cited by 34 publications

(37 citation statements)

References 40 publications

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“…Researchers injected fluorescent tracers into the infarction area of a rodent MCAO stereotactically to evaluate the clearance of solutes, and the results showed that tracers were trapped in the infarct core ( Zbesko et al, 2018 ). Further results from Yang et al (2015) are consistent with this finding ( Lin et al, 2020 ). They used contrast-enhanced MRI by injecting Gd-DTPA into the cisterna magna to assess the GS function in the acute and subacute phases of ischemic stroke induced by MCAO.…”

Section: The Gs Dysfunction In Strokesupporting

confidence: 85%

“…In murine models of acute ischemic stroke (AIS), CSF inflow in the ipsilateral cortex has been verified to be impaired at 3 h after AIS induction via MRI and histological examination (Gaberel et al, 2014). Consistently, researchers found that the influx of CSF was slow even 7 days after ischemic stroke (Lin et al, 2020). However, a recent study found a conflicting conclusion; researchers discovered that the influx of CSF in the GS increased rapidly within minutes of an ischemic insult (Mestre and Du, 2020).…”

Section: Ischemic Strokementioning

confidence: 98%

“…They used contrast-enhanced MRI by injecting Gd-DTPA into the cisterna magna to assess the GS function in the acute and subacute phases of ischemic stroke induced by MCAO. They evaluated the time course of the signal-to-noise ratio (SNR) in the substantia nigra (SNe) and ventral thalamic nucleus (VTN) and found that the SNR time-to-peak on the ipsilateral side was longer in SN both in the acute phase and in the subacute phase than in the contralateral phase ( Lin et al, 2020 ). In addition, the GS dysfunction contributes to the accumulation of toxic solutes and proinflammatory cytokines within the core infarction area.…”

Section: The Gs Dysfunction In Strokementioning

confidence: 99%

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The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Zhao

et al. 2021

Front. Aging Neurosci.

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The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. The complicated network of the GS consists of the periarterial CSF influx pathway, astrocytes-mediated convective transport of fluid and solutes supported by AQP4 water channels, and perivenous efflux pathway. Recent researches indicate that the GS dysfunction is associated with various neurological disorders, including traumatic brain injury, hydrocephalus, epilepsy, migraine, and Alzheimer’s disease (AD). Meanwhile, the GS also plays a pivotal role in the pathophysiological process of stroke, including brain edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, and neuronal apoptosis. In this review, we illustrated the key anatomical structures of the GS, the relationship between the GS and the meningeal lymphatic system, the interaction between the GS and the BBB, and the crosstalk between astrocytes and other GS cellular components. In addition, we contributed to the current knowledge about the role of the GS in the pathology of stroke and the role of AQP4 in stroke. We further discussed the potential use of the GS in early risk assessment, diagnostics, prognostics, and therapeutics of stroke.

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Section: The Gs Dysfunction In Strokesupporting

confidence: 85%

Section: Ischemic Strokementioning

confidence: 98%

Section: The Gs Dysfunction In Strokementioning

confidence: 99%

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The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Zhao

et al. 2021

Front. Aging Neurosci.

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“…In the glymphatic system, the physiological pulsations have been shown to drive water and brain metabolite convection along perivascular spaces and within the brain interstitium in both mice and men (Kiviniemi et al, 2016 ; Meng et al, 2019 ; Mestre et al, 2018 ; Wang et al, 2017 ). Importantly, a failure of glymphatic convection has been shown to precede the onset of neurodegeneration (Iliff et al, 2012 ) and to affect the clinical trajectory of several diseases such as epilepsy, trauma, and stroke (Lin et al, 2020 ; Liu et al, 2020 ; Rasmussen, Mestre, & Nedergaard, 2018 ; Sullan, Asken, Jaffee, DeKosky, & Bauer, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Spectral analysis of physiological brain pulsations affecting the BOLD signal

Raitamaa

Huotari

Korhonen

et al. 2021

Human Brain Mapping

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Physiological pulsations have been shown to affect the global blood oxygen level dependent (BOLD) signal in human brain. While these pulsations have previously been regarded as noise, recent studies show their potential as biomarkers of brain pathology. We used the extended 5 Hz spectral range of magnetic resonance encephalography (MREG) data to investigate spatial and frequency distributions of physiological BOLD signal sources. Amplitude spectra of the global image signals revealed cardiorespiratory envelope modulation (CREM) peaks, in addition to the previously known very low frequency (VLF) and cardiorespiratory pulsations. We then proceeded to extend the amplitude of low frequency fluctuations (ALFF) method to each of these pulsations. The respiratory pulsations were spatially dominating over most brain structures. The VLF pulsations overcame the respiratory pulsations in frontal and parietal gray matter, whereas cardiac and CREM pulsations had this effect in central cerebrospinal fluid (CSF) spaces and major blood vessels. A quasi‐periodic pattern (QPP) analysis showed that the CREM pulsations propagated as waves, with a spatiotemporal pattern differing from that of respiratory pulsations, indicating them to be distinct intracranial physiological phenomenon. In conclusion, the respiration has a dominant effect on the global BOLD signal and directly modulates cardiovascular brain pulsations.

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“…However, this process only works at the very early stage of cerebral ischemia. Studies with longer observation times demonstrated reduced CSF influx within the PVS after ischemic stroke ( 12 , 37 ). Unlike ischemic stroke, cerebral edema is undetectable in the very early stage (5 hours) after SE and usually becomes apparent after 1 day ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus

Liu¹,

Zhu²,

Chang³

et al. 2021

JCI Insight

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Status epilepticus (SE) is a neurological emergency usually accompanied by acute cerebral edema and long-term cognitive impairment, and is characterized by neurodegeneration and aberrant hyperphosphorylated tau protein (p-tau) aggregation. The glia-lymphatic (glymphatic) system plays a central role in facilitating the clearance of metabolic waste from the brain, but its relationship with cerebral edema and cognitive dysfunction after SE is unclear. We hypothesized that cerebral edema after SE might impair glymphatic system function through compression, thus leading to impaired removal of metabolic waste, and ultimately affecting long-term cognitive function. Our results showed that glymphatic system function was temporarily impaired, as evidenced by 2-photon imaging, MRI enhancement, imaging of brain sections, and astrocytic water channel aquaporin 4 (AQP4) protein polarization. The severity of cerebral edema on MRI correlated well with glymphatic system dysfunction within 8 days following SE. Moreover, when cerebral edema was alleviated by glibenclamide treatment or genetic deletion of Trpm4 , post-SE glymphatic system function recovered earlier, along with fewer p-tau–deposited neurons and neuronal degeneration and better cognitive function. These findings suggest that SE-induced cerebral edema may cause glymphatic system dysfunction and render the post-SE brain vulnerable to p-tau aggregation and neurocognitive impairment.

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Impaired glymphatic system in secondary degeneration areas after ischemic stroke in rats

Cited by 34 publications

References 40 publications

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

Spectral analysis of physiological brain pulsations affecting the BOLD signal

Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus

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