4 research outputs found
Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats
Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD). Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3), and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II) and Ang II receptor type 1 (AT1) after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1), as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB) activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor
In Situ Single Photon Confocal Imaging of Cardiomyocyte T-tubule System from Langendorff-Perfused Hearts
Transverse tubules (T-tubules) are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation-contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through in situ confocal imaging of Langendorff-perfused hearts. This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure
Perception of visual apparent motion is modulated by a gap within concurrent auditory glides, even when it is illusory
Auditory and visual events often happen concurrently, and how they group together can have a strong effect on what is perceived. We investigated whether/how intra- or cross-modal temporal grouping influenced the perceptual decision of otherwise ambiguous visual apparent motion. To achieve this, we juxtaposed auditory gap transfer illusion with visual Ternus display. The Ternus display involves a multi-element stimulus that can induce either of two different percepts of apparent motion: ‘element motion’ or ‘group motion’. In element motion, the endmost disk is seen as moving back and forth while the middle disk at the central position remains stationary; while in group motion, both disks appear to move laterally as a whole. The gap transfer illusion refers to the illusory subjective transfer of a short gap (around 100 ms) from the long glide to the short continuous glide when the two glides intercede at the temporal middle point. In our experiments, observers were required to make a perceptual discrimination of Ternus motion in the presence of concurrent auditory glides (with or without a gap inside). Results showed that a gap within a short glide imposed a remarkable effect on separating visual events, and led to a dominant perception of group motion as well. The auditory configuration with gap transfer illusion triggered the same auditory capture effect. Further investigations showed that visual interval which coincided with the gap interval (50-230 ms) in the long glide was perceived to be shorter than that within both the short glide and the ‘gap-transfer’ auditory configurations in the same physical intervals (gaps). The results indicated that auditory temporal perceptual grouping takes priority over the cross-modal interaction in determining the final readout of the visual perception, and the mechanism of selective attention on auditory events also plays a role
The dorsal anterior cingulate cortex modulates dialectical self-thinking
Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants' dispositional level of naïve dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking
