Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

Abstract

Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in the activity of excitatory and inhibitory systems, restores these functions and suppresses the progression of disability in experimental autoimmune encephalitis (EAE). The structural type of TMS, the arrangement as theta burst stimulation (TBS) has been applied as intermittent TBS (iTBS) and continuous TBS (cTBS) protocols to female adult DA rats. The animals were randomly divided into experimental groups: control group (C), group treated with complete Freund's adjuvant (CFA), experimental autoimmune encephalomyelitis (EAE) group, group treated with iTBS post EAE immunization (EAE + iTBS), group treated with cTBS post EAE immunization (EAE + cTBS), group of healthy animals treated with iTBS or cTBS. Therapeutic protocols of iTBS or cTBS in all EAE groups of animals were performed starting from 14 days post immunization (dpi), for 10 days with time point decapitation at 24 dpi. After decapitation, spinal cords were analysed for BDNF and Ki67 expression. The results revealed reduced BDNF expression in the rat's spinal cord of EAE animals in the stage of remission, which was associated with increased Ki67 and GFAP expressions. Decreased Iba 1 and BDNF expression, contrary to increased Iba 1 and Ki67 expression, suggests clustered microglia in the resolution phase of EAE. Enhanced GABA expression in spinal cord sections indicates higher GABA metabolic turnover, and also GAD activity in astrocytes, or prominent activity of GABAergic neurons. Both TBS protocols induced advance BDNF expression; amongst iTBS application provoked elevating of BDNF and stabilizing of GFAP and Ki67 expressions.

Compensatory Neuroprotective Response of Thioredoxin Reductase Against Oxidative-Nitrosative Stress Induced by Experimental Autoimmune Encephalomyelitis in Rats: Modulation by Theta Burst Stimulation

“…DiscussionSubtle pathological changes occur in the brain or spinal cord of rats immunized for EAE before the onset of EAE signs. Astrogliosis has been reported as an underlying mechanism of EAE[12]. Gliosis is usually established after two to three weeks of a CNS injury in rats, which coincided with our results that the peak of the EAE clinical score was achieved at 14dpi and overlapped with the highpoint of ONS measured in the spinal cord of treated rats ([30]).…”

“…It has been shown that repetitive transcranial stimulation arouses remyelination and fosters the expression of neurotrophic factors that are of significant importance for neuro-regeneration in EAE animals [12]. In the cerebral cortex, it may promote neuronal activities in remote zones of the spinal cord, which is interconnected with the main motor pathway -corticospinal tract.…”

“…The underlying neuroprotective role of the Trx/TrxR system may derive from its vigorous release from an astroglia-derived cell line exposed to hydrogen peroxide. Accordingly, the extreme upregulation of TrxR in EAE rats may be explained by the ONS-associated astrogliosis [12,49,50].…”

Continuous versus intermittent theta burst stimulation in the treatment of experimental autoimmune encephalomyelitis: a glutamate transporters study

“…Blood removal from minimizes interferences for immunostaining of microscopic preparations [19]. The assessed experimental outcomes referred to iTBS and cTBS impact on the astroglial glutamate transporters capacity in EAE rats model.…”

“…Decapitation was performed 24 hours after the last TBS treatment. Prior decapitation, all animals were intraperitoneally anesthetized with sodium pentobarbital [19].…”