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Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol
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Objective:To investigate the changes of the functional connectivity of hypothalamus and the whole brain anisotropy in patients with dysphagia after stroke using magnetic resonance imaging. Methods:From December, 2018 to December, 2019, 14 patients with dysphagia after stroke and 15 healthy controls matched in age, sex and dominant hemisphere were selected. The functional connections from bilateral hypothalamus were researched with resting-state functional nuclear magnetic resonance, and the correlation between functional connection and scores of Eating Assessment Tool-10 (EAT-10) was analyzed. Meanwhile, the whole brain white matter integrity was observed with diffusion tensor imaging, and the fraction anisotropy (FA) was compared. Results:Compared with the controls, the functional connections from left hypothalamus to left precentral gyrus, left postcentral gyrus, left marginal lobe, left parietal lobe and left occipital lobe decreased in the patients; while the functional connections to left thalamus, left midbrain and right occipital lobe increased; the functional connections from right hypothalamus to right precentral gyrus, bilateral marginal lobe, bilateral superior temporal gyrus and right parietal lobe decreased; the functional connection to bilateral parietal lobe and bilateral occipital lobe increased. There was negative correlation of EAT-10 scores to functional connection from left hypothalamus to left precentral gyrus (r = -0.595, P = 0.025) and left postcentral gyrus (r = -0.934, P < 0.001), and positive correlation to functional connections from left hypothalamus to left parietal lobe (r = 0.583, P = 0.028) and from right hypothalamus to left occipital lobe (r = 0.630, P = 0.016). Compared with the controls, FA decreased in bilateral precentral gyrus, bilateral postcentral gyrus, bilateral frontal lobe, bilateral parietal lobe, bilateral occipital lobe, bilateral caudate nucleus, bilateral thalamus, right medulla, right superior temporal gyrus, right pontine and left posterior cerebellar lobe in the patients; while FA increased in bilateral anterior lobe of cerebellum and right cingulate gyrus. Conclusion:The motor and sensory cortices are important for swallowing. Patients with dysphagia after stroke may spend more attention and visual compensation. Impairment of white matter is found in swallowing cortex, subcortical structure and brainstem swallowing center in patients with dysphagia after stroke.