Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders

Yao, Di; Zhang, Ruoying; Xie, Mingxing; Ding, Feng; Wang, Minghuan; Wang, Wei

doi:10.1007/s12264-022-00977-9

Cited by 22 publications

(7 citation statements)

References 177 publications

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“…The glymphatic system, an efficient CSF‐ISF exchange mediated by the astrocytic AQP4, serves to remove neurotoxic proteins such as Aβ, tau, and α‐syn from the brain 1,6,27,42,43 . The age‐related evolution of this system has been investigated in elderly rodents 7 and humans 44 .…”

Section: Discussionmentioning

confidence: 99%

“…The glymphatic system, an efficient CSF‐ISF exchange mediated by the astrocytic AQP4, serves to remove neurotoxic proteins such as Aβ, tau, and α‐syn from the brain. 1 , 6 , 27 , 42 , 43 The age‐related evolution of this system has been investigated in elderly rodents 7 and humans. 44 For instance, the glymphatic activity is reported to dramatically decrease in old mice, partly owing to a decrease in arterial pulsatility and loss of AQP4 polarization.…”

Section: Discussionmentioning

confidence: 99%

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Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life

Song,

Li,

Xue

et al. 2024

CNS Neurosci Ther

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IntroductionNeonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown.MethodsNeonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno‐associated virus expressing A53T‐α‐synuclein (α‐syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using in vivo magnetic resonance imaging, ex vivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin‐4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α‐syn overexpression were observed using behavioral tests.ResultsGlymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet‐derived growth factor B (PDGF‐B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α‐syn accumulation was increased and PD‐like symptoms were aggravated in adult NMD mice.ConclusionThe results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF‐B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life

Song,

Li,

Xue

et al. 2024

CNS Neurosci Ther

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“…Being a component of the neurovascular unit (NVU) and glial–vascular unit (GVU), ongoing studies indicate a critical role of microglia in the disruption of perivascular niche and BBB integrity [ 116 , 117 ]. Microglia activated by ischemic stroke can secrete TNF, adipocyte fatty acid-binding protein (A-FABP) and metalloproteinase 9 (MMP-9) to trigger endothelial necroptosis and BBB leakage [ 118 – 120 ].…”

Section: Biological Functions Of Microgliamentioning

confidence: 99%

Noteworthy perspectives on microglia in neuropsychiatric disorders

Zhu,

Guan,

Liu

et al. 2023

J Neuroinflammation

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Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia.

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“…The glymphatic system is a functional system involved in brain cleaning that was first proposed by Nedergaard et al in 2012 [1]. The discovery of this system has led to substantial increases in our understanding of the cerebrospinal fluid (CSF) dynamics in the brain, and many studies have been conducted on this system [2, 3]. This enhanced understanding of the glymphatic system has led to the concept of central nervous system (CNS) interstitial fluidopathy, in which changes in the interstitial fluid (ISF), intracellular fluid, and blood belonging to the CNS fluid have been used to explain many neurological diseases such as sleep disorders, Alzheimer's disease, traumatic brain injury, and small‐vessel disease [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

Kim,

Lee

et al. 2023

Euro J of Neurology

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Background and purposeWe aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti‐seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI‐ALPS).MethodsWe retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as “poor” or “good” ASM responders according to their seizure control at the time of brain MRI. We also included 79 age‐ and sex‐matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI‐ALPS index was calculated using the DSI studio program.ResultsOf the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI‐ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI‐ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI‐ALPS index was negatively correlated with age (r = −0.234, p = 0.019) and duration of epilepsy (r = −0.240, p = 0.016) in patients with focal epilepsy.ConclusionOur study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed.

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Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders

Cited by 22 publications

References 177 publications

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life

Noteworthy perspectives on microglia in neuropsychiatric disorders

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

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