Abstract: Rosmarinic acid, a common ester extracted from Rosemary, Perilla frutescens, and Salvia miltiorrhiza Bunge, has been shown to have protective effects against various diseases. This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury. The right common carotid artery of 3-day-old rats was ligated for 2 hours. The rats were then prewarmed in a plastic container with holes in the lid, which was placed in 37°C water bath for 30 minutes. Afterwards, the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models. The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days. At 22 days after birth, rosmarinic acid was found to improve motor, anxiety, learning and spatial memory impairments induced by hypoxia/ischemia injury. Furthermore, rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone. After hypoxia/ischemia injury, rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure. Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2. These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum. This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University, China (approval No. 20161636721) on September 16, 2017.

Key words: cognitive dysfunction, corpus callosum, differentiation/DNA binding factor 2, hypoxia/ischemia, myelin basic protein, myelin sheath,
remyelination, rosmarinic acid