Interaction between muscle and bone, and improving the effects of electrical muscle stimulation on amyotrophy and bone loss in a denervation rat model via sciatic neurectomy

Abstract

Abstract. The side-to-side difference in bone mineral content and soft tissue composition of extremities and their associations have been observed in patients with stroke and the results are inconsistent. The aim of the present study was to investigate the interaction between bone mineral content (BMC), lean mass (LM) and fat mass (FM) in the paretic extremities in patients following stroke and to determine the effectiveness of electrical muscle stimulation (EMS) following sciatic neurectomy (SN) in rats. BMC, LM and FM were measured by dual-energy X-ray absorptiometry in 61 hemiplegic patients following stroke. In the rat model study, groups of 10 Sprague-Dawley rats were divided into EMS and non-EMS subgroups. Myostatin expression and tetracycline interlabel width were measured. There were significant decreases in BMC, LM and FM in paretic limbs compared to non-paretic limbs. Compared to non-EMS, downregulated myostatin mRNA, and upregulated mechano growth factor (MGF) and insulin-like growth factor 1 (IGF-1) mRNA expression levels were observed in the EMS subgroup (P<0.05). In conclusion, muscle may have an important role in maintaining BMC. EMS-induced muscle contraction effectively downregulated myostatin mRNA, upregulated MGF and IGF-1 mRNA expression in muscle fiber, and mitigated amyotrophy and cortical bone loss from SN. IntroductionThere is a higher risk of bone fracture in patients with stroke compared to the healthy controls. A significant reason for this is the decreased use of paretic extremities, which induced disuse amyotrophy and bone loss (1). In a few previous studies the associations of bone mineral content (BMC) and soft tissue composition of the extremities were observed in patients with stroke and the results were inconsistent (2,3). One of the reasons was that different methodologies for rehabilitation were used.There is a hypothesis that skeletal muscle should not be only treated as a locomotorium, but also as an endocrine organ (4,5). Increasing research over the past 20 years has demonstrated that muscle is a source of myokines that can influence muscle and bone growth in positive or negative ways. Myostatin, insulin-like growth factor 1 (IGF-1) and mechano growth factor (MGF) are three significant myokines, which are produced, expressed and released by muscle fibers following external stimulation, and have their own roles in mediating bone and muscle metabolism by exerting either paracrine or endocrine effects (6-9).The present study was divided to two sections; the clinical research and animal experiment. The clinical research was designed to investigate the association between BMC, lean mass (LM) and fat mass (FM) in the hemiplegic extremities in patients following a stroke, while the animal experiment was designed to determine the effectiveness of electrical muscle stimulation (EMS) to the hindlimbs following sciatic neurectomy (SN) in attenuating disuse amyotrophy and cortical bone loss in Sprague-Dawley female rats by regulating the myostatin, IGF-1, and MGF mRNA or protein expre...

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Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art

“…Animal models support this hypothesis. Muscle is involved in maintaining the bone mineral content and in electrical muscle stimulation following sciatic neurectomy in rats; muscle fibers downregulated myostatin gene expression, a model that should suggest the downregulation of this myokine in stroke-derived paretic limbs [ 95 ]. Cerebral ischemia causes also the activation of the bone morphogenetic protein (BMP)/Smad/5/8 signaling in muscle atrophy occurring following stroke.…”