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Neuroinflammatory Cytokine Response, Neuronal Death, and Microglial Proliferation in the Hippocampus of Rats During the Early Period After Lateral Fluid Percussion-Induced Traumatic Injury of the Neocortex

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Abstract  

Time course of changes in neuroinflammatory processes in the dorsal and ventral hippocampus was studied during the early period after lateral fluid percussion-induced neocortical traumatic brain injury (TBI) in the ipsilateral and contralateral hemispheres. In the ipsilateral hippocampus, neuroinflammation (increase in expression of pro-inflammatory cytokines) was evident from day 1 after TBI and ceased by day 14, while in the contralateral hippocampus, it was mainly limited to the dorsal part on day 1. TBI induced an increase in hippocampal corticosterone level on day 3 bilaterally and an accumulation of Il1b on day 1 in the ipsilateral hippocampus. Activation of microglia was observed from day 7 in different hippocampal areas of both hemispheres. Neuronal cell loss was detected in the ipsilateral dentate gyrus on day 3 and extended to the contralateral hippocampus by day 7 after TBI. The data suggest that TBI results in distant hippocampal damage (delayed neurodegeneration in the dentate gyrus and microglia proliferation in both the ipsilateral and contralateral hippocampus), the time course of this damage being different from that of the neuroinflammatory response.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files). Primary datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Acknowledgements

All authors thank their institutes for the support and encouragements.

Funding

This work was supported by RFBR grants 19–315-90081 (NG, LT) and 19–015-00258 (NG, IK, MN).

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Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485, Moscow, Russia

    Ilia G. Komoltsev, Liya V. Tret’yakova, Stepan O. Frankevich, Natalia I. Shirobokova, Aleksandra A. Volkova, Alexey V. Butuzov, Margarita R. Novikova, Alexey A. Kvichansky, Yulia V. Moiseeva, Mikhail V. Onufriev, Alexey P. Bolshakov & Natalia V. Gulyaeva

  2. Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 115419, Moscow, Russia

    Ilia G. Komoltsev, Stepan O. Frankevich, Mikhail V. Onufriev & Natalia V. Gulyaeva

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  1. Ilia G. Komoltsev
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Contributions

Study concept and design were elaborated by NG and IK. TBI modeling, biomaterial preparation, data collection, and analysis were performed by IK, LT, SF, NS, AV, AB, MN, AK, YM, and MO. The first draft of the manuscript was written by LT, IK, and AK. NG and AB supervised the study and read and accomplished the final version of the manuscript. IK and LT equally contributed to the study.

Corresponding author

Correspondence to Natalia V. Gulyaeva.

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Ethics Approval

All experiments were conducted in compliance with the ARRIVE guidelines and the UK Animals (Scientific Procedures) Act 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, or the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978) and the Ethics Committee of Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences (protocol number 10, December 10, 2012).

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Komoltsev, I.G., Tret’yakova, L.V., Frankevich, S.O. et al. Neuroinflammatory Cytokine Response, Neuronal Death, and Microglial Proliferation in the Hippocampus of Rats During the Early Period After Lateral Fluid Percussion-Induced Traumatic Injury of the Neocortex. Mol Neurobiol 59, 1151–1167 (2022). https://doi.org/10.1007/s12035-021-02668-4

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