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Efficiency of Pexidartinib, an Inhibitor of Receptor Tyrosine Kinases, in Reducing Radiation-Induced Neuroinflammation and Improving Cognitive Functions

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Pharmaceutical Chemistry Journal Aims and scope

Colony-stimulating factor 1 receptor (CSF1R) possesses tyrosine kinase activity. Activation of CSF1R expressed on the surface of brain microglia allows repopulation of microglial cells. Administration of pexidartinib (PD, 40 mg/kg, gavage, 7 d), a CSF1R inhibitor, to mice decreased the number of microglial cells by 90%. Head irradiation at a dose of 8 Gy caused the development of neuroinflammation, as evidenced by the increased fraction of activated microglia in brain-cell preparations, and cognitive impairments two months after the exposure. Administration of PD prior to head irradiation prevented microglia activation. An analysis of episodic memory in the novel-object recognition test and of hippocampus-dependent spatial memory in the Morris water maze test showed that decreasing the number of microglial cells by PD administration prior to irradiation preserved episodic and spatial memory in irradiated mice.

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Authors and Affiliations

  1. National Research Center Kurchatov Institute, 1 Acad. Kurchatov Sq., Moscow, 123182, Russia

    A. V. Rodina, A. S. Zhirnik, Yu. P. Semochkina, O. D. Smirnova, M. G. Ratushnyak, D. A. Shaposhnikova & E. Yu. Moskaleva

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  1. A. V. Rodina
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  2. A. S. Zhirnik
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  3. Yu. P. Semochkina
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  4. O. D. Smirnova
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  5. M. G. Ratushnyak
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  6. D. A. Shaposhnikova
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  7. E. Yu. Moskaleva
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Correspondence to A. V. Rodina.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 57, No. 4, pp. 12 – 16, April, 2023.

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Rodina, A.V., Zhirnik, A.S., Semochkina, Y.P. et al. Efficiency of Pexidartinib, an Inhibitor of Receptor Tyrosine Kinases, in Reducing Radiation-Induced Neuroinflammation and Improving Cognitive Functions. Pharm Chem J 57, 476–480 (2023). https://doi.org/10.1007/s11094-023-02908-y

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  • DOI: https://doi.org/10.1007/s11094-023-02908-y

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