Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-118 |
DRI_Challenge |
denotes |
Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset. |
T2 |
119-326 |
DRI_Outcome |
denotes |
Blood brain barrier (BBB) damage that occurs within the thrombolytic time window is increasingly appreciated to negatively impact the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. |
T3 |
327-451 |
DRI_Challenge |
denotes |
However, the spatiotemporal evolution of BBB damage in this early stroke stage and the underlying mechanisms remain unclear. |
T4 |
452-668 |
DRI_Approach |
denotes |
Here, we investigated the topographical distribution of BBB damage and its association with tissue injury within the first 3 h after ischemia onset and the roles of matrix metalloproteinase (MMP)-2/9 in this process. |
T5 |
669-840 |
DRI_Background |
denotes |
Rats were subjected to 1, 2, or 3 h of middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with fluorescence-labeled dextran as BBB permeability marker. |
T6 |
841-939 |
DRI_Background |
denotes |
Acute tissue infarction was evidenced by staining defect with triphenyltetrazolium chloride (TTC). |
T7 |
940-1009 |
DRI_Background |
denotes |
Cerebral blood flow (CBF) was measured by magnetic resonance imaging. |
T8 |
1010-1062 |
DRI_Background |
denotes |
MMP-2/9 were assessed by gel and in situ zymography. |
T9 |
1063-1068 |
DRI_Unspecified |
denotes |
After |
T10 |
1069-1077 |
Token_Label.OUTSIDE |
denotes |
2-h MCAO |
T11 |
1077-1257 |
DRI_Unspecified |
denotes |
, dextran leakage was seen in the ischemic ventromedial striatum and the preoptic area which showed ~70% CBF reduction, and expanded to other MCA regions including the cortex after |
T12 |
1258-1266 |
Token_Label.OUTSIDE |
denotes |
3-h MCAO |
T13 |
1266-1267 |
DRI_Unspecified |
denotes |
. |
T14 |
1268-1386 |
DRI_Background |
denotes |
Interestingly, high (2000 kDa) and low (70 kDa) molecular weight dextrans displayed almost identical leakage patterns. |
T15 |
1387-1548 |
DRI_Outcome |
denotes |
Different from BBB damage, tissue infarction was first seen in the ischemic dorsal striatum and the parietal/insular cortex which experienced ~90% CBF reduction. |
T16 |
1549-1690 |
DRI_Background |
denotes |
Increased gelatinolytic activity colocalized with dextran leakage, and MMP-2 was found to be the major enzymatic source on gelatin zymograms. |
T17 |
1691-1786 |
DRI_Approach |
denotes |
Pretreatment with MMP inhibitor GM6001 significantly reduced dextran leakage induced by 2-h and |
T18 |
1787-1795 |
Token_Label.OUTSIDE |
denotes |
3-h MCAO |
T19 |
1795-1796 |
DRI_Approach |
denotes |
. |
T20 |
1797-1963 |
DRI_Outcome |
denotes |
Taken together, our findings reveal substantial differences in the topographic distribution of BBB damage and tissue infarction within the first 3 h after MCAO onset. |
T21 |
1964-2140 |
DRI_Challenge |
denotes |
Unlike ischemic neuronal damage, BBB damage appears to develop faster in brain regions with moderately severe ischemia, and MMP-2 contributes to this early ischemic BBB damage. |