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Gastric electrical stimulation improves enteric neuronal survival.

ABSTRACT: Research and clinical experience with vagotomy have confirmed that damage to the central nervous system severely affects physiological movement in the gastrointestinal system. The aim of this study was to investigate the effects of synchronized dual-pulse gastric electrical stimulation (SGES) on the apoptosis of enteric neurons and the possible pathways involved in these effects in vagotomized rats. For this purpose, Male Sprague-Dawley (SD) rats were randomized into a control group, an early subdiaphragmatic vagotomized group (ESDV group), an early subdiaphragmatic vagotomized group with short-term SGES (ESDV + SSGES group), a terminal subdiaphragmatic vagotomized group (TSDV group) and a terminal subdiaphragmatic vagotomized group with long-term SGES (TSDV + LSGES group). The expression levels of connexin 43 (Cx43), glial cell line-derived neurotrophic factor (GDNF), p-Akt, pan-Akt and PGP9.5 were assessed by RT-qPCR, western blot analysis and immunofluorescence staining. Apoptosis was determined by terminal-deoxynucleoitidyl transferase‑mediated nick-end labeling (TUNEL) assay. We found that Cx43 expression was decreased in the ESDV and TSDV groups, but was significantly upregulated in the SSGES and LSGES groups. In addition, the GDNF and PGP9.5 expression levels were significantly decreased in the ESDV group compared with the control and TSDV groups and were upregulated in both the SSGES and LSGES groups. The LSGES group exhibited a clear increase in p-Akt expression compared with the TSDV group. Fewer TUNEL-positive cells were observed in the SSGES and LSGES groups than in the ESDV and TSDV groups. More TUNEL-positive cells were found in the stomach of rats subjected to subdiaphragmatic vagotomy. On the whole, our data indicate that SGES improved enteric neuronal survival, possibly through GDNF and the phosphatidylinositol 3-kinase (PI3K)/Akt pathways.

SUBMITTER: Wang N

PROVIDER: S-EPMC5504986 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and 1) determine the refractory periods of MCs, 2) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and 3) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs. 70.6 ± 15.7 s, P = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% confidence interval (CI) = 2.8-5.7 s, R2 = 0.7315, n = 8). Electrical stimulation applied during fluid distention-evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility.NEW & NOTEWORTHY Maintained physiological distension of the isolated mouse colon induces rhythmic cyclic myoelectric complexes (MCs). MCs evoked repeatedly by closed-loop electrical stimulation entrain MCs more frequently than spontaneously occurring MCs. Electrical stimulation delivered at the onset of a contraction temporarily suppresses the propagation of MC contractions. Controlled electrical stimulation can either evoke MCs or temporarily delay MCs in the isolated mouse colon, depending on timing relative to ongoing activity.

Project description:ObjectiveTo determine if Functional Electrical Stimulation (FES) would improve ischemic pain, walking distance, and quality of life of patients with intermittent claudication.DesignSingle blind, randomized block, two factorial design.PatientsPatients diagnosed with Peripheral Artery Disease (PAD) and intermittent claudication (IC). Ankle Brachial Index ranged 0.4-0.9 on at least one leg. Patients were randomly assigned to experimental (FES+Walk, N=13) or control (WALK, N=14) groups.InterventionExperimental group patients received FES to the dorsiflexor and plantarflexor muscles while walking for 1h/day, six days/week for eight weeks. Control group patients received similar intervention without FES. A Follow-up period of both groups lasted eight weeks.Outcome measuresOutcome measures were taken at baseline (T0), after intervention (T1), and after follow-up (T2). Primary measures included Perceived Pain Intensity (PPI), Six minute walk (6MW), and Peripheral Arterial Disease Quality of Life (PADQOL). Secondary measures included Intermittent Claudication Questionnaire (ICQ) and Timed Up and Go (TUG).ResultsGroup by time interactions in PPI were significant (P<0.001) with differences of 27.9 points at T1 and 36.9 points at T2 favoring the FES+Walk group. Groups difference in Symptoms and Limitations in Physical Function of the PADQOL reached significance (T1=8.9, and T2=8.3 improvements; P=0.007). ICQ was significant (T1=9.3 and T2=13.1 improvements; P=0.003). Improvement in 6MW and TUG tests were similar between groups.Conclusions and relevanceWalking with FES markedly reduced ischemic pain and enhanced QOL compared to just walking. FES while walking may offer an effective treatment option for the elderly with PAD and Intermittent Claudication.Trial registrationNIH-NIA 1R21AG048001 https://projectreporter.nih.gov/project_info_description.cfm?aid=8748641&icde=30695377&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC. https://clinicaltrials.gov/ct2/show/NCT02384980?term=David+Embrey&rank=1.

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Gastric electrical stimulation improves enteric neuronal survival.

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