Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling

Abstract

BackgroundAcupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events.Materials and methodsWe used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models.ResultsBoth WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3β. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice.ConclusionThe results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.

Electroacupuncture exerts prolonged analgesic and neuroprotective effects in a persistent dental pain model induced by multiple dental pulp injuries: GABAergic interneurons-astrocytes interaction

“…To further support our results, we report molecular evidence of various mechanisms associated with persistent orofacial pain that were effectively modulated for at least 49 days after the end of cumulative EA treatment. For instance, mounting evidence suggests that the analgesic effects of EA may be facilitated by the inhibition of glial cells (37). Similarly, our previous study demonstrated that cumulative EA treatment effectively relieved dental pain and inhibited microglial and astrocyte activation (16).…”

“…Mice in the EA groups were initially placed in an induction chamber for 15 min, with the oxygen flow meter adjusted to approximately 2.0 L/min (37). For each 20 min acupuncture session, a mask was connected to a non-rebreathing circuit (Bain) with 1.5% isoflurane (Panion & BF Biotech Inc., Taoyuan, Taiwan).…”

Correlation analysis of serum exosomal miR-133a-3p, miR-206, and miR-549a-3p with diagnosis and prognosis in patients with traumatic head injury

“…BDNF is one of the most widely distributed and widely studied neurotrophic factors in the mammalian brain and is considered a guiding mediator of central nervous system function and structural plasticity, providing the function of effective factors to protect against neurodegeneration 39 . Several studies have shown that BDNF plays an important protective role in TBI and may improve TBI-induced dysfunction 40,41 . Recent studies have shown that BDNF-mediated bone marrow stem cell-derived exosomes protect against TBI through miR-216a-5p and that BDNF-stimulated human umbilical cord mesenchymal stem cell-derived EXO promote remodeling of neural networks after TBI 42,43 .…”