Electroacupuncture promotes neural stem cell proliferation and neurogenesis in the dentate gyrus of rats following stroke via upregulation of Notch1 expression

Abstract

Abstract. Neural stem cells (NSCs) are important in rehabilitation following stroke. Electroacupuncture (EA) treatment has been observed to promote the recovery of neurological functions subsequent to stroke, however, the effects of EA on the proliferation and differentiation of NSCs and its potential mechanisms remain to be elucidated. In the present study, rats, in which a stroke was induced through middle cerebral artery occlusion (MCAO), were treated with EA or control manipulation for 21 days. The modified Neurological Severity score and Morris water maze tests were used to assess the neurological functions of the rats. Bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP) or BrdU/neuronal marker (NeuN) double immunofluorescence staining were used to examine the proliferation and differentiation of the NSCs. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to detect the expression levels of Notch1 and Hes1 in the dentate gyrus (DG) of the hippocampus of rats following MCAO. The results demonstrated that EA treatment significantly improved the neurological functional recovery of rats following stroke. A significant increase was observed in the number of BrdU + /GAFP + and BrdU + /NeuN + cells in the DG area in the EA-treated rats compared with that of the control group. RT-qPCR analysis revealed that EA treatment significantly increased the expression levels of Notch1 and Hes1, which may account for the enhanced proliferation and differentiation of NSCs. In conclusion, to the best of our knowledge, the present study was the first to demonstrate that EA treatment promoted NSC proliferation and neurogenesis in the DG area through the upregulation of Notch signaling following a stroke; therefore, EA may be a useful novel therapeutic strategy in future stroke treatment. IntroductionCerebrovascular diseases are one of the prominent causes of mortality and permanent disability worldwide, the occurrence of which is predicted to further increase due to increasing life expectancies (1). The pharmaceutical industry has developed numerous potential neuroprotective drugs for the treatment of stroke, which have been observed to decrease cerebral damage and enhance the recovery of motor and cognitive abilities following ischemic insult in preclinical studies using animal models. However, these results have not been reproduced in phase III clinical trials and none of the assessed compounds led to the successful post-ischemic treatment of patients (2,3). Therefore, further investigation in this field is required in order to examine novel therapeutic strategies, which may ameliorate the recovery of post-ischemic patients.Stem cells, with self-renewal and pluripotent differentiation potentials, are a promising source for tissue regeneration, including neural regeneration (4). Neural stem cells (NSCs) have been identified in the subventricular zone (SVZ) and dentate gyrus (DG) of adult brain and these NSCs proliferate and generate neurons throughout the a...

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

“…1I, K). This inconsistency might be ascribed to some factors induced by hypoxia that are involved in hypoxia-induced neurogenesis such as Notch 1 signaling [33][34][35]. Notch 1 is known to be crucial for the self-renewal and fate-decision of NSCs and promotes ischemia-induced neurogenesis in the hippocampus by cleaving Notch 1 and increasing the level of NICD (notch intracellular domain), the active form of Notch 1 that translocates to the nucleus and regulates transcription [36,37].…”

Combined Effects of Electroacupuncture and Behavioral Training on Learning-Memory Ability and Event-Related Potential P300 in Rats with Mid/Advanced Cerebral Infarction

“…[ 23 ] Animal experiments have confirmed that continuous EA stimulation can improve the cerebral blood flow, confront free radical damage, inhibit cell apoptosis, reduce nerve cell damage, regulate neurotransmitters, promote angiogenesis, regulate vasoactive substances, promote secretion and metabolism of brain neurotransmitters, and regulate the inhibitory status of the ischemic cortex, thus increasing its compensatory function, promoting the ordering of EEG activities, and improving the basic electrical activities of the cortical cells. [ 24 25 26 27 ] The experimental rats' brain perception capacity can thus be increased, their brain execution function is enhanced, and their ability of processing external information and regulating behaviors are also promoted. In this study, we have found that the P latency in the M/ACI rats is shortened, while the amplitude is increased, and the learning-memory ability in the Y-maze is also improved.…”

Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

“…Pretreatment or treatment of EA worked against cerebral ischemia and reperfusion damage through regulation of neuronal excitotoxicity, apoptosis, oxidative stress, and inflammation in ischemic stroke [ 37 – 39 ]. It had also been shown that EA took definite benefits on the improvement of neural repairing after stroke [ 40 – 42 ]. In addition, the study by Chuang et al stated that EA intervention at the acute stage of TBI resulted in a decrease of transforming growth-interacting factor in injured area and an increase of the regional cerebral blood flow in rats, which contributed to reduce neuronal apoptosis and improve neurological outcomes posttrauma [ 43 ].…”