Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy

Semyachkina-Glushkovskaya, O.; Fedosov, Ivan V.; Shirokov, Alexander; Водовозова, Е. Л.; Алексеева, А. С.; Khorovodov, Alexander; Blokhina, Inna; Terskov, Andrey; Mamedova, Aysel; Klimova, Maria; Dubrovsky, Alexander; Ageev, Vasily; Agranovich, Ilana; Vinnik, Valeria; Tsven, Anna; Sokolovski, Sergey; Rafailov, Edik U.; Penzel, Thomas; Kurths, Jürgen

doi:10.1515/nanoph-2021-0212

Cited by 25 publications

(69 citation statements)

References 43 publications

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“…These data reflect the FAβ distribution from the ventricle to the basal MLVs, playing an important role in the brain drainage and clearance [16,17,[30][31][32][33]. The dcLNs are the first anatomical station of the CSF exit with dissolved unneeded substances for the brain [16,17,[30][31][32][33]. Therefore, the more intensively the substance is released from the brain, the stronger is its level in dcLNs.…”

Section: Ps-mediated Stimulation Of Lymphatic Clearance Of Faβ From the Mouse Brain At Night And During The Daymentioning

confidence: 80%

“…Figure 2e shows that the spread of FAβ was higher on the ventral than on the dorsal aspect of the brain 3 h after its injection. These data reflect the FAβ distribution from the ventricle to the basal MLVs, playing an important role in the brain drainage and clearance [16,17,[30][31][32][33]. The dcLNs are the first anatomical station of the CSF exit with dissolved unneeded substances for the brain [16,17,[30][31][32][33].…”

Section: Ps-mediated Stimulation Of Lymphatic Clearance Of Faβ From the Mouse Brain At Night And During The Daymentioning

confidence: 82%

“…In our previous works, we studied the mechanisms of the PS effects on the lymphatics. Our data demonstrate that PS induces relaxation of the lymphatic vessels, which is associated with an increase in the permeability of the lymphatic endothelium [ 30 , 31 , 32 , 35 ]. We show that a decrease in the transepithelial electrical resistance and in the expression of tight junction (TJ) proteins, such as CLDN-5, VE-cadherin, and ZO-1, might be a possible mechanism underlying a PS-mediated increase in the lymphatic permeability.…”

Section: Discussionmentioning

confidence: 99%

“…PS increases the lymphatic contractility [ 30 , 35 ] that is regulated by NO [ 62 , 63 ]. Our recent findings show that PS dilates the MLVs and increases NO production in the isolated lymphatic endothelial cells, which is associated with an increase in the lymphangion contraction [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, there has been accumulating evidence suggesting that PS can reduce Aβ-mediated hippocampal neurodegeneration and memory impairments in rodents, inhibit Aβ-induced brain cell apoptosis, and cause reduction in Aβ plaques in the cerebral cortex [ 26 , 27 , 28 , 29 ]. In our previous animal experiments, we clearly showed that PS effectively stimulates the clearing function of the meningeal lymphatic vessels (MLVs), which play a crucial role in Aβ clearance [ 30 , 31 , 32 , 33 ]. We also demonstrated that the course of PS during 9 days effectively reduces the Aβ level in mice with AD [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

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Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

Semyachkina-Glushkovskaya

Penzel

Blokhina

et al. 2021

Cells

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The deposition of amyloid-β (Aβ) in the brain is a risk factor for Alzheimer’s disease (AD). Therefore, new strategies for the stimulation of Aβ clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aβ removal from the brain. There is increasing evidence that sleep plays an important role in Aβ clearance. Here, we tested our hypothesis that PS at night can stimulate Aβ clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aβ clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aβ accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aβ accumulation in the brain of people with disorder of Aβ metabolism, sleep deficit, elderly age, and jet lag.

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Section: Ps-mediated Stimulation Of Lymphatic Clearance Of Faβ From the Mouse Brain At Night And During The Daymentioning

confidence: 80%

Section: Ps-mediated Stimulation Of Lymphatic Clearance Of Faβ From the Mouse Brain At Night And During The Daymentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

Semyachkina-Glushkovskaya

Penzel

Blokhina

et al. 2021

Cells

Self Cite

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Mechanisms of Photostimulation of Brain’s Waste Disposal System: The Role of Singlet Oxygen

Semyachkina-Glushkovskaya,

Bragin,

Fedosov

et al. 2023

Advances in Experimental Medicine and Biology

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A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer’s Disease

Shan,

Lu,

Luo

et al. 2024

ACS Nano

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Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aβ accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

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Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy

Cited by 25 publications

References 43 publications

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

Mechanisms of Photostimulation of Brain’s Waste Disposal System: The Role of Singlet Oxygen

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer’s Disease

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