TY - JOUR A1 - Schuhmann, Michael K. A1 - Stoll, Guido A1 - Bohr, Arne A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Electrical stimulation of the mesencephalic locomotor region attenuates neuronal loss and cytokine expression in the perifocal region of photothrombotic stroke in rats JF - International Journal of Molecular Science N2 - 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. KW - photothrombotic stroke KW - deep brain stimulation KW - mesencephalic locomotor region KW - neuroprotection KW - neuronal apoptosis KW - neuroinflammation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201355 SN - 1422-0067 VL - 20 IS - 9 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Stoll, Guido A1 - Papp, Lena A1 - Bohr, Arne A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Electrical stimulation of the mesencephalic locomotor region has no impact on blood–brain barrier alterations after cerebral photothrombosis in rats JF - International Journal of Molecular Science N2 - Blood–brain barrier (BBB) disruption is a critical event after ischemic stroke, which results in edema formation and hemorrhagic transformation of infarcted tissue. BBB dysfunction following stroke is partly mediated by proinflammatory agents. We recently have shown that high frequency stimulation of the mesencephalic locomotor region (MLR-HFS) exerts an antiapoptotic and anti-inflammatory effect in the border zone of cerebral photothrombotic stroke in rats. Whether MLR-HFS also has an impact on BBB dysfunction in the early stage of stroke is unknown. In this study, rats were subjected to photothrombotic stroke of the sensorimotor cortex and implantation of a stimulating microelectrode into the ipsilesional MLR. Thereafter, either HFS or sham stimulation of the MLR was applied for 24 h. After scarifying the rats, BBB disruption was assessed by determining albumin extravasation and tight junction integrity (claudin 3, claudin 5, and occludin) using Western blot analyses and immunohistochemistry. In addition, by applying zymography, expression of pro-metalloproteinase-9 (pro-MMP-9) was analyzed. No differences were found regarding infarct size and BBB dysfunction between stimulated and unstimulated animals 24 h after induction of stroke. Our results indicate that MLR-HFS neither improves nor worsens the damaged BBB after stroke. Attenuating cytokines/chemokines in the perilesional area, as mediated by MLR-HFS, tend to play a less significant role in preventing the BBB integrity. KW - photothrombotic stroke KW - deep brain stimulation KW - mesencephalic locomotor region KW - blood-brain barrier KW - tight junctions Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201284 SN - 1422-0067 VL - 20 IS - 16 ER - TY - THES A1 - Bohr, Arne T1 - Über den Einfluss einer kontinuierlichen tiefen Hirnstimulation des pedunkulopontinen tegmentalen Nucleus auf motorische Defizite in einem Ratten-Schlaganfallmodell T1 - Deep Brain Stimulation for Stroke: Continuous Stimulation of the Pedunculopontine Tegmental Nucleus has no Impact on Skilled Walking in Rats After Photothrombotic Stroke N2 - Bei einem ischämischen Schlaganfall bestehen neben dem Verlust von neuronalen Zellen auch dysfunktionale Signale, die sich pathologisch auf die tieferen motorischen Zentren des zentralen Nervensystems auswirken können. Mittels tiefer Hirnstimulation kann die Weiterleitung pathologischer Signale im Bereich des neuronalen Netzwerks unterbrochen werden. In dieser Arbeit wurde ein Tiermodell verwendet, in welchem bei insgesamt 18 Ratten ein photothrombotischer Schlaganfall des rechten sensomotorischen Kortex induziert wurde. Nachdem bei jedem Tier eine Mikroelektrode in den Bereich des pedunkulopontinen tegmentalen Nucleus implantiert worden war, wurde eine kontinuierliche tiefe Hirnstimulation über 10 Tage durchgeführt. Die Gegenüberstellung der Fall- und Kontrollgruppe im Beam-Walking- und Ladder-Rung-Walking-Test ergab hierbei keine Verbesserung der motorischen Defizite durch die Intervention. Das Ergebnis lässt sich vor dem Hintergrund neuerer Erkenntnisse einordnen, nach welchen der pedunkulopontine tegmentale Nucleus nicht für die Bewegungsinitiierung verantwortlich ist. N2 - Abstract: Background: Gait impairment after stroke is considered as a loss of cerebral function but is also the result of dysfunctional cerebral signals travelling to the spinal motor centres. A therapeutic option to restore disturbed cerebral network activity is deep brain stimulation (DBS). Methods: A promising target for neuromodulation might be the pedunculopontine tegmental nucleus (PPTg), which contributes to the initiation and control of gait. To test this hypothesis, we trained eighteen rats to cross a horizontal ladder and a wooden beam before inflicting a photothrombosis in the right sensorimotor cortex and implanting a stimulating electrode in the ipsilateral PPTg. Results: Continuous high-frequency DBS (130 Hz; amplitude 55 ± 5 μA) of rats for 10 days yielded no significant improvement of skilled walking when examined with the ladder rung walking test and beam walking test compared to sham-stimulation. Conclusion: In contrast to DBS of the cuneiform nucleus, PPTg-stimulation improves neither control of gait nor balance after stroke. KW - Schlaganfall KW - Hirnstimulation KW - Tiefe Hirnstimulation KW - Ischämischer Schlaganfall KW - Ladder-Rung-Walking-Test KW - Beam-Walking-Test KW - Photothrombotic Stroke KW - Deep Brain Stimulation KW - Mesencephal Locomotor Region KW - Mesenzephale Lokomotor Region KW - Pedunculopontiner tegmentaler Nukleus Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271876 PB - Current Neurovascular Research ER -