Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were essential to protect against blood-brain barrier (BBB) disruption after ischemia by regulating the activities of MMPs. We confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and TIMP-2 in focal ischemia, using TIMP-1 À/À and TIMP-2 À/À mice. TIMP-1 mRNA expression was gradually increased until 24 h after reperfusion. In TIMP-1 À/À mice, MMP-9 protein expression and gelatinolytic activity were significantly more augmented after cerebral ischemia than those in WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions and the degree of ischemic injury despite an increased Evans blue leakage. These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia.
Transplantation of stem cells has the possibility of restoring neural functions after stroke damage. Therefore, we transplanted neuronal progenitors generated from monkey embryonic stem (ES) cells into the ischemic mouse brain to test this possibility. Monkey ES cells were caused to differentiate into neuronal progenitors by the stromal cell-derived inducing activity method. Focal cerebral ischemia was induced by occluding the middle cerebral artery by the intraluminal filament technique. The donor cells were transplanted into the ischemic lateral striatum at 24 h after the start of reperfusion. The cells transplanted into the ischemic brain became located widely around the ischemic area, and, moreover, the transplanted cells differentiated into various types of neurons and glial cells. Furthermore, at 28 days after the transplantation, over 10 times more cells in the graft were labeled with Fluorogold (FG) by stereotactic focal injection of FG into the anterior thalamus and substantia nigra on the grafted side when compared with the number at 14 days. From these results we confirmed the survival and differentiation of, as well as network formation by, monkey ES-cell-derived neuronal progenitors transplanted into the ischemic mouse brain.
Abstract:To evaluate the effects of hillslope topography on storm runoff in a weathered granite mountain, discharge rate, soil pore water pressures, and water chemistry were observed on two types of hillslope: a valley-head (a concave hillslope) and a side slope (a planar hillslope). Hydrological responses on the valley-head and side slope reflected their respective topographic characteristics and varied with the rainfall magnitude. During small rainfall events (<35 mm), runoff from the side slope occurred rapidly relative to the valley-head. The valley-head showed little response in storm runoff. As rainfall amounts increased (35-60 mm), the valley-head yielded a higher flow relative to the side slope. For large rainfall events (>60 mm), runoff from both hillslopes increased with rainfall, although that from the valley-head was larger than that from the side slope. The differences in the runoff responses were caused by differences in the roles of lower-slope soils and the convergence of the hillslope. During small rainfall events, the side slope could store little water; in contrast, all rainwater could be stored in the soils at the valley-head hollow. As the amount of rainfall increased, the subsurface saturated area of the valley-head extended from the bottom to the upper portion of the slope, with the contributions of transient groundwater via lateral preferential flowpaths due to the high concentration of subsurface water. Conversely, saturated subsurface flow did not contribute to runoff responses, and the subsurface saturated area at the side slope did not extend to the upper slope for the same storm size. During large rainfall events, expansion of the subsurface saturated area was observed in both hillslopes. Thus, differences in the concentration of subsurface water, reflecting hillslope topography, may create differences in the extension of the subsurface saturated area, as well as variability in runoff responses.
Our results indicate that the MCA specimens from MMD patients had thicker intimal walls than the specimens from control patients. In addition, hypoxia-inducing factor-1alpha and endoglin were overexpressed in the intima of the MCA of MMD patients.
[1] Understanding a discharge hydrograph is one of the leading interests in catchment hydrology. Recent research has provided credible information on the importance of bedrock groundwater on discharge hydrographs from headwater catchments. However, intensive monitoring of bedrock groundwater is rare in mountains with steep topography. Hence, how bedrock groundwater controls discharge from a steep headwater catchment is in dispute. In this study, we conducted long-term hydrological observations using densely located bedrock wells in a headwater catchment underlain by granitic bedrock. The catchment has steep topography affected by diastrophic activities. Results showed a fairly regionalized distribution of bedrock aquifers within a scale of tens of meters, consisting of upper, middle, and lower aquifers, instead of a gradual and continuous decline in water level from ridge to valley bottom. This was presumably attributable to the unique bedrock structure; fault lines developed in the watershed worked to form divides between the bedrock aquifers. Spatial expanse of each aquifer and the interaction among aquifers were key factors to explain gentle and considerable variations in the base flow discharge and triplepeak discharge responses of the observed hydrograph. A simple model was developed to simulate the discharge hydrograph, which computed each of the contributions from the soil mantle groundwater, from the lower aquifer, and from the middle aquifer to the discharge. The modeling results generally succeeded in reproducing the observed hydrograph. Thus, this study demonstrated that understanding regionalized bedrock aquifer distribution is pivotal for explaining discharge hydrograph from headwater catchments that have been affected by diastrophic activities.Citation: Kosugi, K., M. Fujimoto, S. Katsura, H. Kato, Y. Sando, and T. Mizuyama (2011), Localized bedrock aquifer distribution explains discharge from a headwater catchment, Water Resour. Res., 47, W07530,
Groundwater movements in volcanic mountains and their effects on streamflow discharge and representative elementary area (REA) have remained largely unclear. We surveyed the discharge and chemical composition of spring and stream water in two catchments: the Hontani river (NR) catchment (6.6 km2) and the Hosotani river (SR) catchment (4.0 km2) at the southern part of Daisen volcano, Japan. Daisen volcano is a young volcano (17 × 103 years) at an early stage of erosion. Our study indicated that deep groundwater that moved through thick lava and pyroclastic flows and that could not be explained by shallow movements controlled by surface topography contributed dominantly to streamflow at larger catchment areas. At the NR catchment, the deep groundwater contribution clearly increased at a catchment boundary defined by an area of 3.0 km2 and an elevation of 800 m. At the SR catchment, the contribution deep groundwater to the stream also increased suddenly at a boundary threshold of 2.0 and 700 m. Beyond these thresholds, the contributions of deep bedrock groundwater remained constant, indicating that the REA is between 2 and 3 km2 at the observed area. These results indicate that the hydrological conditions of base flow were controlled mainly by the deep bedrock groundwater that moved through thick lava and pyroclastic flows in the undissected volcanic body of the upper part of the catchment. Our study demonstrates that deep and long groundwater movements via a deep bedrock layer including thick deposits of volcanic materials at the two catchments on Daisen volcano strongly determined streamflow discharge instead of the mixing of small‐scale hydrological conditions. Copyright © 2015 John Wiley & Sons, Ltd.
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