Therapeutic Efficiency of Proteins Secreted by Glial Progenitor Cells in a Rat Model of Traumatic Brain Injury

Traumatic brain injuries account for 30–50% of all physical traumas and are the most common pathological diseases of the brain. Mechanical damage of brain tissue leads to the disruption of the blood–brain barrier and the massive death of neuronal, glial, and endothelial cells. These events trigger a neuroinflammatory response and neurodegenerative processes locally and in distant parts of the brain and promote cognitive impairment. Effective instruments to restore neural tissue in traumatic brain injury are lacking. Glial cells are the main auxiliary cells of the nervous system, supporting homeostasis and ensuring the protection of neurons through contact and paracrine mechanisms. The glial cells’ secretome may be considered as a means to support the regeneration of nervous tissue. Consequently, this study focused on the therapeutic efficiency of composite proteins with a molecular weight of 5–100 kDa secreted by glial progenitor cells in a rat model of traumatic brain injury. The characterization of proteins below 100 kDa secreted by glial progenitor cells was evaluated by proteomic analysis. Therapeutic effects were assessed by neurological outcomes, measurement of the damage volume by MRI, and an evaluation of the neurodegenerative, apoptotic, and inflammation markers in different areas of the brain. Intranasal infusions of the composite protein product facilitated the functional recovery of the experimental animals by decreasing the inflammation and apoptotic processes, preventing neurodegenerative processes by reducing the amounts of phosphorylated Tau isoforms Ser396 and Thr205. Consistently, our findings support the further consideration of glial secretomes for clinical use in TBI, notably in such aspects as dose-dependent effects and standardization. © 2023 by the authors.

Authors
Salikhova D.I. , Golovicheva V.V. , Fatkhudinov T.K. , Shevtsova Y.A. , Soboleva A.G. , Goryunov K.V. , Dyakonov A.S. , Mokroysova V.O. , Mingaleva N.S. , Shedenkova M.O. , Makhnach O.V. , Kutsev S.I. , Chekhonin V.P. , Silachev D.N. , Goldshtein D.V.
Publisher
MDPI AG
Issue number
15
Language
English
State
Published
Number
12341
Volume
24
Year
2023
Organizations
  • 1 Institute of Molecular and Cellular Medicine, RUDN University, Moscow, 117198, Russian Federation
  • 2 Research Centre for Medical Genetics, Moscow, 115478, Russian Federation
  • 3 A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russian Federation
  • 4 Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Moscow, 117418, Russian Federation
  • 5 V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, 117997, Russian Federation
  • 6 Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russian Federation
  • 7 Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, 119034, Russian Federation
Keywords
glial cells; iPSCs; proteomic analysis; secretome; traumatic brain injury
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