Electrical Stimulation of the Mesencephalic Locomotor Region Attenuates Neuronal Loss and Cytokine Expression in the Perifocal Region of Photothrombotic Stroke in Rats.

Michael K. Schuhmann,Arne Bohr,Jens Volkmann,Felix Fluri,Guido Stoll

doi:10.3390/ijms20092341

Michael K. Schuhmann, Arne Bohr + Show 3 more

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https://doi.org/10.3390/ijms20092341

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Abstract

Deep brain stimulation of the mesencephalic locomotor region (MLR) improves the motor symptoms in Parkinson’s disease and experimental stroke by intervening in the motor cerebral network. Whether high-frequency stimulation (HFS) of the MLR is involved in non-motor processes, such as neuroprotection and inflammation in the area surrounding the photothrombotic lesion, has not been elucidated. This study evaluates whether MLR-HFS exerts an anti-apoptotic and anti-inflammatory effect on the border zone of cerebral photothrombotic stroke. Rats underwent photothrombotic stroke of the right sensorimotor cortex and the implantation of a microelectrode into the ipsilesional MLR. After intervention, either HFS or sham stimulation of the MLR was applied for 24 h. The infarct volumes were calculated from consecutive brain sections. Neuronal apoptosis was analyzed by TUNEL staining. Flow cytometry and immunohistochemistry determined the perilesional inflammatory response. Neuronal apoptosis was significantly reduced in the ischemic penumbra after MLR-HFS, whereas the infarct volumes did not differ between the groups. MLR-HFS significantly reduced the release of cytokines and chemokines within the ischemic penumbra. MLR-HFS is neuroprotective and it reduces pro-inflammatory mediators in the area that surrounds the photothrombotic stroke without changing the number of immune cells, which indicates that MLR-HFS enables the function of inflammatory cells to be altered on a molecular level.

Highlights

Considerable progress has been achieved in the treatment of acute ischemic stroke by the introduction of mechanical thrombectomy [1]
In a first set of experiments, we assessed whether mesencephalic locomotor region (MLR)-high-frequency stimulation (HFS) in rats had an impact on lesion size after photothrombotic stroke
hematoxylin and eosin (HE) staining yielded a slight variability of electrode placement in relation to midbrain structures, with non-visible tissue damage, except for the electrode tracks toward the MLR

Summary

Introduction

Considerable progress has been achieved in the treatment of acute ischemic stroke by the introduction of mechanical thrombectomy [1]. Around 86% of all stroke survivors present permanent limb paresis, and up to 11% are no longer able to walk, even after intensive physical training [3] This might be due to limited neuroplasticity, but it might be a result of local processes around the infarcted brain area, such as neuroinflammation. We have shown that high-frequency stimulation (HFS) of the mesencephalic locomotor region (MLR) enables gait restoration after photothrombotic lesioning of the sensorimotor cortex in rats [4]. We examined the effect of MLR-HFS on apoptotic and inflammatory processes in the peri-infarcted brain region (sensorimotor cortex) of male Wistar rats within the first 24 h after stroke onset, with these considerations in mind

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