Abstract:
Traumatic Brain Injury (TBI) is a complex and multifactorial pathology,
being a major cause of death and disability for humans. Immediately after TBI,
astrocytes and microglia react with complex morphological and functional changes
known as reactive gliosis and forms, in the area immediately adjacent to the lesion, the
glial scar, the major barrier to neuronal regeneration in the central nervous system.
The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis
leaves, has been shown to have neurogenic, neuroprotective, and anti-inflammatory
effects, demonstrated in vitro models of glutamate-induced toxicity, neuroinflammation,
and demyelination. The present study investigated, the effect of agathisflavone in
neuronal integrity and in the modulation of gliosis in ex vivo models of TBI.
Methodology: Microdissections from the encephalon of Wistar rats (P6-8), were
prepared and subjected to mechanical injury (MI) and treated or not daily with
agathisflavone (5 μM) for 3 days. Astrocyte reactivity was investigated by measuring
mRNA and expression of GFAP protein in the lesioned area by immunofluorecence
and westernblot; proportion of microglia was determined by immunofluorescence for
Iba-1; mRNA expression for inflammasome NRPL3 and interleukin -1 beta (IL-1β) was
determined by RT-qPCR. Results: It was observed that lesion of the cortical tissue
induced astrocytes over expressing GFAP in the typical glial scar formed, and
agathisflavone modulated GFAP expression at transcriptional and pos-transcriptional
level associated with reduction of glial scar. MI induced increase in the proportion of
microglia (Iba-1+) that was not observed in agathisflavone treated cultures. Moreover,
the flavonoid modulated negatively both NRLP3 and IL-1β mRNA expression that was
increases in the lesioned area of the tissue. Conclusion: All of these findings reiterate
the regulatory property of the inflammatory response of glial cells by the flavonoid
agathisflavone, which can impact in neuroprotection and should be considered for
future pre-clinical and clinical studies for CNS pathologies, including TBI.
