Microphysiological systems for studying neuroplasticity and cerebral microcirculation

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Abstract

This review systematizes modern bioengineering strategies for modeling tissue barriers, neurovascular unit (NVU) and perivascular unit (PVU) for translational neuroscience. The aim is to provide a critical analysis of the current understandings of neuroplasticity, organization of NVU, PVU and blood-brain barrier as well as advantages and limitations of currently available in vitro microphysiological models. It is clear that, despite progress in replicating three-dimensional architecture, the next key challenge is to imitate the temporal dynamics of histogenesis (angiogenesis, barrierogenesis, neurogenesis). This defines the transition towards the development of a novel class of 4D models capable of spatiotemporal self-organization. The analysis reveals the necessity to adapt model complexity to the target function: highly complex systems are a priority for fundamental research into plasticity and pathogenesis of nervous system disorders, while standardized platforms are well-suited for high-throughput pharmacological screening. It is concluded that creating relevant, validated platforms remains a critical interdisciplinary task. This will help bridge the gap between preclinical and clinical research, enhancing the reliability of studying pathological mechanisms and the preclinical evaluation of therapeutic agents.

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About the authors

Alla B. Salmina

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Author for correspondence.
Email: allasalmina@mail.ru
ORCID iD: 0000-0003-4012-6348
SPIN-code: 6504-7657

MD, PhD, Professor, Corresponding Member of the RAS

Russian Federation, Moscow; Moscow

Anton S. Averchuk

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: antonaverchuk@yandex.ru
ORCID iD: 0000-0002-1284-6711
SPIN-code: 7276-8713

PhD in Biology, Assistant Professor

Russian Federation, Moscow; Moscow

Yulia K. Komleva

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: yuliakomleva@mail.ru
ORCID iD: 0000-0001-5742-8356
SPIN-code: 1585-8130

MD, PhD

Russian Federation, Moscow; Moscow

Natalia A. Kolotyeva

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: bortnikova.n@gmail.com
SPIN-code: 5815-0989

MD, PhD, Assistant Professor

Russian Federation, Moscow; Moscow

Natalia A. Rozanova

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: nataliarozanovaa@gmail.com
ORCID iD: 0000-0001-9619-4679
SPIN-code: 7696-1738
Russian Federation, Moscow; Moscow

Ilya V. Potapenko

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: iluminator@snkip.ru
ORCID iD: 0000-0001-9743-8700
SPIN-code: 4229-9507

PhD 

Russian Federation, Moscow; Moscow

Olga P. Alexandrova

Russian Сenter of Neurology and Neurosciences

Email: molka-molka@yandex.ru
ORCID iD: 0009-0006-9109-1463
SPIN-code: 2705-7186

PhD in Biology

Russian Federation, Moscow

Dmitry A. Lifanov

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: dmtlifnv@gmail.com
ORCID iD: 0009-0001-6127-8044
SPIN-code: 5367-8372
Russian Federation, Moscow; Moscow

Denis A. Abaimov

Russian Сenter of Neurology and Neurosciences; Moscow State Technical University named after N.E. Bauman

Email: abaimov@neurology.ru
ORCID iD: 0000-0001-6888-3223
SPIN-code: 7548-0933

PhD in Biology

Russian Federation, Moscow; Moscow

Maksim A. Dragun

Moscow State Technical University named after N.E. Bauman

Email: drmaksim@icloud.com
ORCID iD: 0000-0002-2319-4894
SPIN-code: 5400-0828
Russian Federation, Moscow

Ivan A. Kushnir

Moscow State Technical University named after N.E. Bauman

Email: ivankushnir.x@gmail.com
ORCID iD: 0009-0007-5034-6244
SPIN-code: 2083-6046
Russian Federation, Moscow

Sofia A. Korsakovа

Moscow State Technical University named after N.E. Bauman

Email: sofia.korsakova@gmail.com
ORCID iD: 0000-0001-9269-8300
SPIN-code: 6918-5588
Russian Federation, Moscow

Stanislav O. Yurchenko

Moscow State Technical University named after N.E. Bauman

Email: st.yurchenko@mail.ru
ORCID iD: 0000-0001-6821-904X
SPIN-code: 3313-1005

PhD in Physical and Mathematical Sciences, Professor

Russian Federation, Moscow

Sergey N. Illarioshkin

Russian Сenter of Neurology and Neurosciences

Email: illarioshkin@neurology.ru
ORCID iD: 0000-0002-2704-6282
SPIN-code: 8646-9426

MD, PhD, Professor, Academician of the RAS

Russian Federation, Moscow

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2. Fig. 1. Microphysiological systems for solving current clinical problems Note. BBB — blood-brain barrier; NVE — neurovascular unit; PVE — perivascular unit.

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3. Fig. 2. Schematic diagram of the neurovascular (A) and perivascular (B) units with images of the main cellular components: 1, 11 — astrocyte end stalk; 2 — pia mater; 3 — Virchow-Robin space; 4 — perivascular macrophage; 5 — smooth muscle cells; 6, 12 — basement membrane; 7, 14 — endothelial cell; 8, 15 — blood vessel lumen; 9 — neuron cell body; 10 — microglial cell; 13 — pericyte

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