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Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

ABSTRACT: Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

SUBMITTER: Wu Z

PROVIDER: S-EPMC7538419 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

Wu Zheng Z Sun Fangling F Li Zijie Z Liu Min M Tian Xin X Guo Deyu D Wei Penghu P Shan Yongzhi Y Liu Tingting T Guo Min M Zhu Zixin Z Zheng Wenrong W Wang Yufeng Y Zhao Guoguang G Wang Wen W

Scientific reports 20201006 1

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the l ...[more]

PMID: 33024145

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Project description:Background Electrical stimulation of the cerebellar fastigial nucleus (FNS) has been shown to protect animals against cerebral ischemic injury. However, the changes in cortical activation as a response to FNS have not been illustrated in humans. Objective This study aims to detect functional connectivity changes in the brain of stroke patients, and investigate the cortical activation caused by FNS through measuring the oxygenated hemoglobin concentration (HBO) in the cerebral cortex of stroke patients and healthy controls (HCs). Methods This study recruited 20 patients with stroke and 20 HCs with all the following factors matched: age, gender and BMI. The experiment session was made up of the pre-task baseline, FNS task period, and post-task baseline. FNS task period contains 5 blocks, each block encompassing the resting state (30 s) and the FNS state (30 s). HBO signals were acquired by functional near-infrared spectroscopy (fNIRS) from the Prefrontal Cortex (PFC), the Motor Cortex (MC) and the Occipital Cortex (OC) throughout the experiment. The Pearson correlation coefficient was used to calculate the resting-state functional connectivity strength between the two groups, and the general linear model (GLM) was used to calculate the activation of 39 fNIRS channels during FNS in stroke patients and HCs, respectively. Results The coupling strength of stroke patients were significantly decreased in the following regions: right MC and left MC (t = 4.65, p = 0.0007), right MC and left OC (t = 2.93, p = 0.04), left MC and left OC (t = 2.81, p = 0.04). In stroke patients, the changes in cerebral oxygenated hemoglobin (ΔHBO) among 12 channels (CH) in the bilateral PFC and bilateral MC regions were significantly increased during the FNS state (FDR corrected p < 0.05) compared with the resting state. In HCs, only 1 channel was increased (FDR corrected p < 0.05) in the left PFC during FNS. Conclusion By using the FNS and fNIRS techniques, the characteristics of functional connectivity were found to decrease in stroke patients. It was also noticed that FNS activates the PFC and MC regions. These findings may help to guide functional rehabilitation in stroke patients.

Project description:BackgroundThe vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN) as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications, but the anti-inflammatory efficacy of electrical DMN stimulation (eDMNS) was not previously investigated. Here, we examined the effects of eDMNS on heart rate (HR) and cytokine levels in murine endotoxemia as well as the cecal ligation and puncture (CLP) model of sepsis.MethodsAnesthetized male 8-10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (50, 250 or 500 μA and 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24h after CLP. CLP survival was monitored for 14 days.ResultsEither left or right eDMNS at 250 μA and 500 μA decreased HR, compared with pre- and post-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and were not associated with serum corticosterone alterations. Right side eDMNS suppressed serum TNF levels but had no effects on serum IL-10 and on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum TNF and IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice.ConclusionsFor the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation and these effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.

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Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

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Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

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