Beschreibung: Background and Purpose— Aside from the primary motor cortex, the corticospinal tract (CST) also receives fibers from dorsal and ventral premotor cortices and supplementary motor area, all of which might potentially contribute to motor function after stroke. We sought to quantify the microstructural integrity of CST originating from the hand representations in these 4 motor cortices separately and examined how these values related to hand motor impairment. Methods— Probabilistic tractography from functional MRI-defined cortical sites demonstrated continuous CST originating from hand representations within each motor area in a group of healthy subjects. Microstructural integrity for each tract was calculated using fractional anisotropy at the level of the posterior limb of the internal capsule in a group of patients with chronic stroke. Results— Fractional anisotropy was reduced in all 4 CSTs in the affected hemisphere. Grip strength correlated with the integrity of the CSTs originating from primary motor and dorsal premotor cortices, whereas, in a multiple regression model, the latter improved the ability of primary motor cortex CST to explain variability in grip strength. Conclusion— Handgrip critically depends on the CST originating in primary motor cortex but microstructural integrity of CST originating from premotor cortices appears to play a role in supporting motor function after stroke.

Beschreibung: Monoamine oxidases (MAOs) generate H 2 O 2 as a by-product of their catalytic cycle. Whether MAOs are mediators of endothelial dysfunction is unknown and was determined here in the angiotensin II and lipopolysaccharide-models of vascular dysfunction in mice. Quantitative real-time polymerase chain reaction revealed that mouse aortas contain enzymes involved in catecholamine generation and MAO-A and MAO-B mRNA. MAO-A and -B proteins could be detected by Western blot not only in mouse aortas but also in human umbilical vein endothelial cells. Ex vivo incubation of mouse aorta with recombinant MAO-A increased H 2 O 2 formation and induced endothelial dysfunction that was attenuated by polyethylene glycol-catalase and MAO inhibitors. In vivo lipopolysaccharide (8 mg/kg IP overnight) or angiotensin II (1 mg/kg per day, 2 weeks, minipump) treatment induced vascular MAO-A and -B expressions and resulted in attenuated endothelium-dependent relaxation of the aorta in response to acetylcholine. MAO inhibitors reduced the lipopolysaccharide- and angiotensin II–induced aortic reactive oxygen species formation by 50% (ferrous oxidation xylenol orange assay) and partially normalized endothelium-dependent relaxation. MAO-A and MAO-B inhibitors had an additive effect; combined application completely restored endothelium-dependent relaxation. To determine how MAO-dependent H 2 O 2 formation induces endothelial dysfunction, cyclic GMP was measured. Histamine stimulation of human umbilical vein endothelial cells to activate endothelial NO synthase resulted in an increase in cyclic GMP, which was almost abrogated by MAO-A exposure. MAO inhibition prevented this effect, suggesting that MAO-induced H 2 O 2 formation is sufficient to attenuate endothelial NO release. Thus, MAO-A and MAO-B are both expressed in the mouse aorta, induced by in vivo lipopolysaccharide and angiotensin II treatment and contribute via the generation of H 2 O 2 to endothelial dysfunction in vascular disease models.

Beschreibung: Background and Purpose— Ischemic strokes with motor deficits lead to widespread changes in neural activity and interregional coupling between primary and secondary motor areas. Compared with frontal circuits, the knowledge is still limited to what extent parietal cortices and their interactions with frontal motor areas undergo plastic changes and might contribute to residual motor functioning after stroke. Methods— Fifteen well-recovered patients were evaluated 3 months after stroke by means of functional magnetic resonance imaging while performing visually guided hand grips with their paretic hand. Dynamic causal modeling was used to investigate task-related effective connectivity between ipsilesional posterior parietal regions along the intraparietal sulcus and frontal key motor areas, such as the primary motor cortex, the ventral premotor cortex, and the supplementary motor area. Results— Compared with healthy controls of similar age and sex, we observed significantly enhanced reciprocal facilitatory connectivity between the primary motor cortex and the anterior intraparietal sulcus of the ipsilesional hemisphere. Beyond that and as a fingerprint of excellent recovery, the coupling pattern of the parietofrontal network was near-normal. An association between coupling parameters and clinical scores was not detected. Conclusions— The present analysis further adds to the understanding of the parietofrontal network of the ipsilesional hemisphere as a prominent circuit involved in plastic changes after stroke.