The effect of extremely low frequency electromagnetic fields on the proliferation and differentiation of endogenous neural stem cells in rats with cerebral ischemia

Abstract

Traumatic brain injury (TBI) is the head injury caused by a direct or indirect external force, which is very common in disaster victims hitting by falling of heavy objects. Cerebral ischemia is discussed as one secondary injury mechanism that may participate in TBI. In recent decades, a focus on the neuroplasticity of the brain provides a brand-new research direction with regard to the recovery of brain damage. Neural stem cells (NSCs) which are mainly generated in the subgranular zone (SGZ) and the subventricular zone (SVZ) play an important role in the process of self-repair and neuroplasticity of the brain and represent a main line of current research. The Notch signaling pathway regulated the proliferation and differentiation of NSCs. When the Notch signaling pathway is upgraded, the expression of the key factors of the pathway including Hes1, Hes5 and Notch1 will be increased, the number of NSCs might be increased. A number of studies have found that extremely low frequency electromagnetic fields (ELF-EMF) can promote the differentiation of NSCs in vitro or in healthy adult rats. Experimental results also show that ELF-EMF could become an important treatment strategy in regenerative medicine. However, reports on the effect of ELF-EMF in cerebral ischemia are still lacking, and the underlying mechanism remains unclear. In this experiment, Longa's MCAO surgery was performed to establish the animal model of ischemia brain injury. Sprague-Dawley (SD) rats were divided into sham-surgery group, control group and experiment group randomly, the last two groups received Longa's MCAO surgery. The experiment group further received ELF-EMF (50Hz, 1mT) intervention. Then in different time points, mNSS, De Ryck's Scale and Morris water maze were used to assess neurological function, BrdU labeling method was applied to observe the NSCs' proliferation and differentiation and the new born neurons, RT-PCR and Western blot analysis were used to analyze gene and protein expression of Notch1, Hes1 and Hes5 in the SVZ and SGZ. The results showed that ELF-EMF (50Hz, 1mT) : 1) significantly improved learning ability and memory, however had no significant effect on mNSS and De Ryck's scores in rats with cerebral ischemia; 2) significantly promoted the proliferation and differentiation of NSCs, and increased the number of new born neurons in SVZ and SGZ in rats with cerebral ischemia; 3) significantly increased the expression of Hes1, Hes5 and Notch1 in the SVZ and SGZ and 4) probably promoted the proliferation and differentiation of NSCs by regulating the Notch signaling pathway in cerebral ischemia. These findings provide a theoretical basis for the application of ELF-EMF in cerebral ischemia. ELF-EMF may be benefit for TBI and ischemic diseases in central never system.