Agathisflavone modulates astrocytic responses and increases the population of neurons in an in vitro model of traumatic
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ORIGINAL ARTICLE
Agathisflavone modulates astrocytic responses and increases the population of neurons in an in vitro model of traumatic brain injury Vanessa Cristina Meira de Amorim 1 & Markley Silva Oliveira Júnior 1 & Alessandra Bispo da Silva 1 & Jorge M. David 2 & Juceni Pereira Lima David 3 & Maria de Fátima Dias Costa 1 & Arthur Morgan Butt 4 & Victor Diogenes Amaral da Silva 1 & Silvia Lima Costa 1 Received: 13 September 2019 / Accepted: 10 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Flavonoids . Agathisflavone . 6,8”-Bisapigenin . NGF . GDNF
Introduction Traumatic brain injury (TBI) is a critical health problem worldwide, with a high incidence rate and potentially severe
* Silvia Lima Costa [email protected] 1
Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon, Salvador, BA 40100-902, Brazil
2
Department of General and Inorganic Chemistry, Institute of Chemistry, Federal University of Bahia, R. Barão de Jeremoabo, Salvador, BA 40170-115, Brazil
3
Department of Medication, Faculty of Pharmacy, Federal University of Bahia, R. Barão de Jeremoabo, Salvador, BA 40170-115, Brazil
4
School of Pharmacy and Biomedical Science, University of Portsmouth, Winston Churchill Avenue, Portsmouth PO1 2UP, UK
long-term consequences (Langlois et al. 2006; Helmy et al. 201
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