Cerebral small vessel disease: from a focal to a global perspective

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(7), P. 387 - 398

Published: May 25, 2018

Language: Английский

---

Impaired glymphatic function and clearance of tau in an Alzheimer’s disease model

Brain, Journal Year: 2020, Volume and Issue: 143(8), P. 2576 - 2593

Published: May 14, 2020

Abstract The glymphatic system, that is aquaporin 4 (AQP4) facilitated exchange of CSF with interstitial fluid (ISF), may provide a clearance pathway for protein species such as amyloid-β and tau, which accumulate in the brain Alzheimer’s disease. Further, tau transference via extracellular space, compartment cleared by pathway, allows its neuron-to-neuron propagation, regional progression tauopathy disorder. system therefore represents an exciting new target Here we aim to understand involvement CSF-ISF pathology. First, demonstrate impaired AQP4 polarization mouse model tauopathy, suggesting this have potential exacerbate or even induce pathogenic accumulation tau. Subsequently, establish central role from brain; showing marked using novel inhibitor, TGN-020. As such, show presents druggable treatment disease, possibly other neurodegenerative diseases alike.

Language: Английский

---

Development and plasticity of meningeal lymphatic vessels

The Journal of Experimental Medicine, Journal Year: 2017, Volume and Issue: 214(12), P. 3645 - 3667

Published: Nov. 15, 2017

The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement neuropathological processes, yet little is known about development or maintenance. We show here that LVs develop postnatally, appearing first around the foramina basal parts skull and spinal canal, sprouting along blood cranial nerves to various meninges surrounding central nervous system (CNS). VEGF-C, expressed mainly vascular smooth muscle cells, VEGFR3 endothelial cells were essential for development, whereas VEGF-D deletion had no effect. Surprisingly, adult mice, showed regression after VEGF-C deletion, administration tyrosine kinase inhibitor sunitinib, expression VEGF-C/D trap, which also compromised drainage function. Conversely, an excess induced lymphangiogenesis. plasticity regenerative potential should allow manipulation cerebrospinal fluid processes CNS.

Language: Английский

---

Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

---

Astrocyte Heterogeneity: Impact to Brain Aging and Disease

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: March 19, 2019

Astrocytes, one of the largest glial cell population in Central Nervous System, play key function several events brain development and function, such as synapse formation control neurotransmitters release uptake, production trophic factors neuronal survival. Initially described a homogenous population, evidences have pointed that astrocytes are highly heterogeneous, both morphologically functionally, within same region, across different regions. Recent findings suggest heterogeneity expression profile proteins involved astrocyte may predict selective vulnerability regions to specific diseases, well age-related cognitive decline. However, molecular mechanisms underlying these changes, either aging disease scarce. Neuroinflammation, hallmark neurodegenerative diseases aging, is reported dubious impact on activation, cells pro- anti-inflammatory cytokines chemokines, anti-oxidants, free radicals, neurotrophic factors. Despite emerging evidence supporting reactive duality their phenotype, neurotoxic or neuroprotective properties, depending age stimuli, cellular interplays regional still matter discussion. In this review, we will summarize recent phenotypes, likely for during neural diseases. We focus molecules triggered by Finally, discuss new how modulation phenotype could synaptic deficits dysfunction present pathological states.

Language: Английский

---