Browsing by Author "Obermann, Mark"

Lithium at serum concentrations up to 1 mmol/L has been used in patients suffering from bipolar disorder for decades and has recently been shown to reduce the risk for ischemic stroke in these patients. The risk for stroke and thromboembolism depend not only on cerebral but also on general endothelial function and health; the entire endothelium as an organ is therefore pathophysiologically relevant. Regardless, the knowledge about the direct impact of lithium on endothelial function remains poor. We conducted an experimental study using lithium as pharmacologic pretreatment for murine, porcine and human vascular endothelium. We predominantly investigated endothelial vasorelaxation capacities in addition to human basal and dynamic (thrombin-/PAR-1 receptor agonist-impaired) barrier functioning including myosin light chain (MLC) phosphorylation (MLC-P). Low-dose therapeutic lithium concentrations (0.4 mmol/L) significantly augment the cholinergic endothelium-dependent vasorelaxation capacities of cerebral and thoracic arteries, independently of central and autonomic nerve system influences. Similar concentrations of lithium (0.2-0.4 mmol/L) significantly stabilized the dynamic thrombin -induced and PAR-1 receptor agonist-induced permeability of human endothelium, while even the basal permeability appeared to be stabilized. The lithium attenuated dynamic permeability was mediated by a reduced endothelial MLC-P known to be followed by a lessening of endothelial cell contraction and paracellular gap formation. The well-known lithium-associated inhibition of inositol monophosphatase/glycogen synthase kinase-3-beta signaling-pathways involving intracellular calcium concentrations in neurons seems to similarly occur in endothelial cells, too, but with different down-stream effects such as MLC-P reduction. This is the first study discovering low dose lithium as a drug directly stabilizing human endothelium and ubiquitously augmenting cholinergic endothelium-mediated vasorelaxation. Our findings have translational and potentially clinical impact on cardiovascular and cerebrovascular disease associated with inflammation explaining why lithium can reduce, e.g., the risk for stroke. However, further clinical studies are warranted.

Objective: The study was conducted to investigate the after-effect of transcranial direct current stimulation (tDCS) applied over the human primary motor cortex (M1) on trigeminal and extracranial nociceptive processing. Basic procedures: Nineteen healthy volunteers were stimulated using cathodal, anodal (both 1 mA) or sham tDCS for 20 minutes. Pain processing was assessed by recording trigeminal and extracranial pain-related evoked potentials (PREPs) following electrical stimulation of the contralateral forehead and hand at baseline, 0, 20 and 50 minutes post-tDCS. Main findings: Cathodal tDCS resulted in decreased peak-to-peak amplitudes (PPAs) by 18% while anodal tDCS lead to increased PPAs of PREPs by 35% (p <. 05). Principal conclusions: The decreased PPAs suggest an inhibition and the increased PPAs of PREPs suggest an excitation of trigeminal and extracranial pain processing induced by tDCS of the M1. These results may provide evidence for the effectiveness of tDCS as a therapeutic instrument in treating headache disorders.