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Administration of all‐ trans retinoic acid after experimental traumatic brain injury is brain protective
Author(s) -
Hummel Regina,
Ulbrich Sebastian,
Appel Dominik,
Li Shuailong,
Hirnet Tobias,
Zander Sonja,
Bobkiewicz Wieslawa,
Gölz Christina,
Schäfer Michael K.E.
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15259
Subject(s) - astrogliosis , traumatic brain injury , medicine , neuroprotection , gliosis , microglia , brain damage , hippocampal formation , lesion , pharmacology , pathology , central nervous system , inflammation , psychiatry
Background and Purpose All‐ trans retinoic acid (ATRA) is a vitamin A metabolite, important in the developing and mature brain. Pre‐injury ATRA administration ameliorates ischaemic brain insults in rodents. This study examined the effects of post‐traumatic ATRA treatment in experimental traumatic brain injury (TBI). Experimental Approach Male adult mice were subjected to the controlled cortical impact model of TBI or sham procedure and killed at 7 or 30 days post‐injury (dpi). ATRA (10 mg kg−1, i.p.) was given immediately after the injury and 1, 2 and 3 dpi. Neurological function and sensorimotor coordination were evaluated. Brains were processed for (immuno‐) histological, mRNA and protein analyses (qPCR and western blot). Key Results ATRA treatment reduced brain lesion size, reactive astrogliosis and axonal injury at 7 dpi, and hippocampal granule cell layer (GCL) integrity was protected at 7 and 30 dpi, independent of cell proliferation in neurogenic niches and blood–brain barrier damage. Neurological and motor deficits over time and the brain tissue loss at 30 dpi were not affected by ATRA treatment. ATRA decreased gene expression of markers for damage‐associated molecular pattern (HMGB1), apoptosis (caspase‐3 and Bax), activated microglia (TSPO), and reactive astrogliosis (GFAP, SerpinA3N) at 7 dpi and a subset of markers at 30 dpi (TSPO, GFAP). Conclusion and Implications In experimental TBI, post‐traumatic ATRA administration exerted brain protective effects, including long‐term protection of GCL integrity, but did not affect neurological and motor deficits. Further investigations are required to optimize treatment regimens to enhance ATRA's brain protective effects and improve outcomes.