Acupuncture Ameliorates Cognitive Dysfunction by Modulating the Apoptosis of Hippocampal Neuron in Severe Hand Foot and Mouth Disease Infant Rats Through the p38 MAPK/CREB Pathway

The infection of Enterovirus A 71 (EV-A71) could cause severe hand-foot-mouth disease (HFMD), which poses a grave threat to the lives of children. Moreover, in some cases where the children survive, long-term neurological sequelae may occur. Acupuncture can alleviate cognitive dysfunction, however, its role in HFMD has not been investigated. HFMD models caused by EV-A71 infection were constructed in Sprague-Dawley infant rats. Morris water maze test was employed to evaluate the spatial learning and memory function administered by the interventions of SB203580 or/and acupuncture. The changes and apoptosis degree of hippocampus tissues were evaluated by H&E staining and TUNEL staining assay. Furthermore, the western blot was utilized to detect the apoptosis-related proteins as well as the proteins involved in the p38 MAPK/CREB pathway within the tissues. After induction with EV-A71, compared to the control group, the rat's escape latency increased noticeably, while the time duration spent on the platform and the number of platform-crossing times decreased significantly. Moreover, in the hippocampal tissues of EV-A71-infected rats, pyramidal cells were loosely arranged, of different sizes and disorganized, as well as the numbers of neuronal cell apoptosis were significantly elevated, accompanied by increased expression of phosphorylated p38 and down-regulations of phosphorylated CREB. Interestingly, these effects could be relieved by acupuncture or SB203580 intervention, and acupuncture could additionally enhance the influence of SB203580. Acupuncture might modulate the p38 MAPK/CREB pathway, thus alleviating the impairment of spatial learning and memory, as well as the apoptosis in the hippocampus of rats infected with EV-A71.