Abstract
Traumatic brain injury (TBI) is a critical health problem worldwide, with a high incidence rate and potentially severe long-term consequences. Depending on the level of mechanical stress, astrocytes react with complex morphological and functional changes known as reactive astrogliosis. In cases of severe tissue injury, astrocytes proliferate in the area immediately adjacent to the lesion to form the glial scar, which is a major barrier to neuronal regeneration in the central nervous system. The flavonoid agathisflavone has been shown to have neuroprotective, neurogenic, and immunomodulatory effects and could have beneficial effects in situations of TBI. In this study, we investigated the effects of agathisflavone on modulating the responses of astrocytes and neurons to injury, using the in vitro scratch wound model of TBI in primary cultures of rat cerebral cortex. In control conditions, the scratch wound induced an astroglial injury response, characterized by upregulation of glial fibrillary acidic protein (GFAP) and hypertrophy, together with the reduction in proportion of neurons within the lesion site. Treatment with agathisflavone (1 μM) decreased astroglial GFAP expression and hypertrophy and induced an increase in the number of neurons and neurite outgrowth into the lesion site. Agathisflavone also induced increased expression of the neurotrophic factors NGF and GDNF, which are associated with the neuroprotective profile of glial cells. These results demonstrate that in an in vitro model of TBI, the flavonoid agathisflavone modulates the astrocytic injury response and glial scar formation, stimulating neural recomposition.
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Acknowledgments
This work was supported by the Coordination of Personnel Improvement of Higher Level (CAPES, PGCI-Process No. 88881.117666/2016-01), the Foundation for Research Support of the State of Bahia (Process No. INT 0016/2016), the National Council for Scientific and Technological Development (CNPq, MCTI/CNPq/Universal 14/2014 Process 443723/2014-1), and the INCT/CNPq for Excitotoxicity and Neuroprotection. We would like to thank the Laboratory of Neurochemistry and Cell Biology and the Postgraduate Program in Animal Science in the Tropics of the Federal University of Bahia for the support and CAPES for the Master fellowships to VCMA (Process 0001).
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VCMA performed all the experimentation, analyzed and interpreted the data, and was a major contributor in writing the manuscript. MSOJ and ABS helped with the maintenance of the cell culture and to perform RT-qPCR. JMD and JPD performed the chemical extraction of the flavonoid agathisflavone. MFDC, VDAS, and AMB revised it critically for intellectual content. SLC supervised the stud and edited and reviewed the manuscript. All authors read and approved the final manuscript.
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de Amorim, V.C.M., Júnior, M.S.O., da Silva, A.B. et al. Agathisflavone modulates astrocytic responses and increases the population of neurons in an in vitro model of traumatic brain injury. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1921–1930 (2020). https://doi.org/10.1007/s00210-020-01905-2
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DOI: https://doi.org/10.1007/s00210-020-01905-2