Abstract
Significance:
Low frequency whole body vibration (LFV) at 40 Hz, a low impact form of exercise, for a month following mild transient middle-cerebral artery occlusion (tMCAO) reduces infarct volume and improves motor function in reproductively senescent, middle-aged female rats (1). In humans, LFV was shown to increase circulating levels of irisin, a skeletal muscle-derived hormone. Irisin has also been shown to play a crucial role in preserving mitochondrial function, preventing oxidative stress, and elevating expression of BDNF, among other neuroprotective measures. The current study aims to investigate the efficacy of LFV in ameliorating post-tMCAO cognitive deficits and to determine the putative role of irisin in conferring the benefits of LFV in middle-aged rats.
Methods:
Middle-aged rats of both sexes (5-8) were randomly assigned to tMCAO (90 min), or sham surgery followed by exposure to either LFV (twice a day for 15 min each for 5 days a week over a month) or no LFV treatment groups. Following the last LFV treatment, rats were tested for hippocampus-dependent learning and memory using a water maze followed harvesting brain and blood samples for histopathological and inflammatory marker analyses, respectively. In a parallel experiment in the absence of LFV, middle-aged female rats were randomly assigned to either saline or irisin treatment following tMCAO. Recombinant irisin was purchased from PeproTech (Rocky Hill, NJ). Rats were treated with irisin (0.2 μg/g BW; IP) or saline for a month followed by their brains were assessed by histopathology.
Results:
Post-tMCAO LFV significantly lessens cognitive deficits in rats of both sexes. It also significantly decreased circulating pro-inflammatory cytokines and increased serum levels of native irisin. Quantification of infarct volume irisin-treated rats demonstrated that, compared to saline, infarct volume was significantly reduced. Saline treatment resulted in 234 ± 30 mm
3
, while irisin treatment yielded 128 ± 34 mm
3
(p<0.05) of infarct volume.
Conclusion:
Irisin, either as elicited by LFV or administered exogenously without LFV, regulates brain metabolism and inflammation and its beneficial effects can be stimulated by LFV.Reference: 1. Raval, A.P., et al., Int J Mol Sci, 2018.
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