http://www.sciencedirect.com/science/article/pii/S0361923017302381
Highlights
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- Rehabilitation training reduced apoptosis of hippocampal neurons.
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- Rehabilitation training activated PI3K/Akt and Nrf2/ARE signaling pathways.
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- Activated PI3K/Akt and Nrf2/ARE pathways improved neural and motor functions.
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- Activated PI3K/Akt and Nrf2/ARE pathways reduced apoptosis of hippocampal neurons.
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- Rehabilitation training is an effective treatment for neural deficits.
Abstract
This
study was designed in order to investigate the effects between
rehabilitation training on the apoptosis of nerve cells and the recovery
of neural and motor functions of rats with ischemic stroke by way of
the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and
nuclear factor E2-related factor 2/antioxidant responsive element
(Nrf2/ARE) signaling pathways. In total, 110 healthy adult male
Sprague-Dawley (SD) rats were selected in order to take part in this
study. Ninety SD rats were used in order to establish the middle
cerebral artery occlusion (MCAO), among which 80 rats were randomly
assigned as part of the natural recovery, natural recovery + Rp-PI3K
(the rats injected with PI3K/Akt inhibitor LY294002), rehabilitation
training, and rehabilitation training + Rp-PI3K groups. Meanwhile, 20
rats were selected as part of the sham operation group. The neural and
motor functions of these rats were evaluated using a balance beam test
and the Bederson score. The mRNA expressions of PI3K, Akt, Nrf2 and HO-1
were measured using an RT-qPCR. The protein expressions of PI3K,
p-PI3K, Akt, p-Akt, Nrf2 and HO-1 were also detected by using western
blotting and the immunohistochemistry process. The cell cycle and cell
apoptosis were detected by using a flow cytometry and TUNEL assay. The
sham operation group exhibited lower neural and motor function scores
than other groups. At the 7, 14, and 21 d marks of this study, the
neural and motor function scores were increased in the natural recovery,
natural recovery + Rp-PI3K, and rehabilitation training + Rp-PI3K
groups in comparison with the rehabilitation training group but found to
be decreased in the natural recovery group in comparison with the
natural recovery + Rp-PI3K group. In comparison with the sham operation
group, expressions of PI3K, Nrf2 and HO-1, and proportions of
p-PI3 K/PI3 K and p-Akt/Akt were all higher in the natural recovery,
rehabilitation training, and rehabilitation training + Rp-PI3K groups.
Same trends were found in the rehabilitation training group in
comparison with the natural recovery and rehabilitation
training + Rp-PI3K groups, as well as in the natural recovery group in
comparison with the natural recovery + Rp-PI3K group. In comparison with
the sham operation and rehabilitation training groups, hippocampal
nerve cells at G1 phase and the cells apoptosis were both elevated in
the other three groups which were found to be decreased in the natural
recovery group in comparison with the natural recovery + Rp-PI3K group.
Our results indicated that the rehabilitation training can inhibit the
apoptosis of nerve cells as well as promote the recovery of both neural
and motor functions in rats with ischemic stroke by activation of the
PI3K/Akt and Nrf2/ARE signaling pathways.
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