Clinical and microscopic analysis of cellular-molecular communications in focal cortical dysplasia IIIс

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Abstract

Cortical dyslamination with neuronal dysmorphism that occurs adjacent to an arteriovenous malformation (AVM) and is accompanied by epilepsy (E) is classified as FCD IIIc. Its etiology and pathogenesis have yet to be determined.

Objective: to clarify the cellular composition and expression of various receptors in the AVM and its perifocal zone with and without FCD IIIc

Material and methods. A morphological study of the surgical material of the brain of 14 patients with FCD IIIc and 13 patients with AVM without E was carried out using antibodies to: Ang1, Ang2, Ki-67, MHC1, CD34, NeuroD1, NG2, CD117, PrgRc, ErgRc, SSTR2, GH, SMA, GFAP and electron microscopy of the AVM of 1 patient with FCD IIIc.

Results. There were CD34+ endotheliocytes, CD34+/CD117+/NeuroD1+ telocytes, SMA+ smooth muscle cells, NG2+ pericytes in the walls of AVM vessels with E and without it. A scar zone of CD117+-telocytes forming a 3D structure was determined in 50% of patients with FCD IIIc and in 46% with AVMs. Electron microscopy confirmed the presence of pericytes and telocytes in the small AVM vessels. In no case was the expression of PrgRc, ErgRc, and GH, while SSTR2 was detected in vascular cells of all AVMs and the perifocal zone. The expression level of MHC1 was statistically significantly higher in the AVM vessels than around the vessels (p<0.001), and NeuroD1 was higher in the AVM vessels than in the vascular kidneys (p<0.001), while there were significantly more NG2+-pericytes in the perifocal zone than in AVM (p=0.02), and CD117+-telocytes – in AVM and perifocal zone than in vascular kidneys (p<0.001).

Conclusion. Our study made it possible to clarify the cellular composition of the AVM and its perifocal zone, revealing pericytes and telocytes; did not reveal differences in malformation with and without E. The pronounced expression of SSTR2 in AVM opens up new possibilities for therapy with somatostatin analogs.

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About the authors

Lyubov B. Mitrofanova

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Email: lubamitr@yandex.ru

associate professor Research Laboratory of Pathomorphology, head department of Pathological Anatomy, pathologist of the pathoanatomical department, Almazov National Medical Research Centre, doctor of Medical Sciences, professor

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

Zaur M. Rasulov

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Email: zaurneuro@yandex.ru

postgraduate student Department of Neurosurgery Almazov National Medical Research Centre

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

Olga M. Vorobeva

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Email: olgarasp@yandex.ru

pathologist of the pathoanatomical Department of the Clinic, associate professor of the Department of Pathological Anatomy, Almazov National Medical Research Centre, candidate of medical sciences

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

Andrey N. Gorshkov

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Email: angorsh@yahoo.com

head of the Laboratory of Intracellular Transport and Signaling Smorodintsev Research Institute of Influenza, senior researcher, Research Laboratory of Pathomorphology, Almazov National Medical Research Centre, candidate of biological sciences

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

Ksenia A. Sterkhova

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Email: ks.sterhova@gmail.com
ORCID iD: 0009-0000-0623-0040

resident, Almazov National Medical Research Centre

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

Alexey Yu. Ulitin

FSBI «NMIC named after V.A. Almazov»; FGBU «A.A. Smorodintsev Influenza Research Institute»

Author for correspondence.
Email: ulitinaleks@mail.ru
ORCID iD: 0000-0002-8343-4917

head of the Department of Neurosurgery, Almazov National Medical Research Centre, doctor of Medical Sciences, professor

Russian Federation, Akkuratova str., 2, St. Petersburg, 197341; Prof. Popov str., 15/17, St. Petersburg, 197022

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2. Fig. 1. AVM without association with epilepsy: a – brain tissue between dilated vessels. b – Vessels of the perifocal zone with embolizate in the walls (black); stained with hematoxylin and eosin. c, d – Tears (indicated by arrows) and lysis of elastic fibers with their absence over a large extent of the wall and hemorrhage (highlighted by an oval); coloring according to Weigert – van Gieson. e, f – Discomplexation and uneven distribution of smooth muscle cells (expression of SMA) with their complete absence in some areas (circled); ×100

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3. Fig. 2. Patient K., 32 years old with FCD IIIc. a – Ang1; b – Ang 2 on AVM vessel wall cells. c – MHC1; d – CD34; e – NG2; f – NeuroD1 (vascular kidneys are circled), g – CD117, h – Ki-67 in vascular kidney cells; ×200

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4. Fig. 3. AVM without epilepsy. a – AVM with embolization (black embolizate in the lumen of vessels) with CD34 expression on telocytes along the outer edge of the vessel (arrowed); ×100. b – Expression of NG2 on pericytes of the wall of a large vessel; ×200

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5. Fig. 4. AVM without epilepsy. a – Expression of CD117 on scar telocytes forming a 3D structure in the perifocal zone; b – Expression of CD117 on telocytes located along the outer edge of the vessel walls; ×400; c, d – Expression of GFAP on glia surrounding AVM; ×100; e – Expression of NeuroD1 on telocytes in the scar zone; ×200; f – Expression of CD34 on scar telocytes; ×100

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6. Fig. 5. Electron microscopy of the AVM of the patient with FCD IIIc. a–c – vessels with perivascular cells (pericytes and telocytes). Micrographs show edematous extracellular matrix without organized collagen structures. d – area of cell necrosis. Symbols: E – endothelium, EC – erythrocytes, EM – extracellular matrix.

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7. Fig. 6. Patient S. 43 years old with FCD IIIc. Expression of somatostatin receptors SSTR2: a – in the cells of the walls of blood vessels (indicated by arrows) and b – in vascular kidneys (circled); ×200

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8. Fig. 7. Distribution diagrams: a – MHC1 in AVM (1) and perifocal zone (2); b – NG2+-pericytes in AVM (1) and perifocal zone (2)

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