TY - JOUR
T1 - Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats
T2 - Correlation with brain edema
AU - Wu, He
AU - Zhang, Zhiyi
AU - Li, Ying
AU - Zhao, Ruibo
AU - Li, Heng
AU - Song, Yuejia
AU - Qi, Jiping
AU - Wang, Jian
N1 - Funding Information:
This work was supported by the Natural Science Foundation of Heilongjiang Province ZJY0705 and the Foundation of the First Clinical Hospital of Harbin Medical University Y08-009 (HW) and by AHA 09BGIA2080137 and NIH K01AG031926 (JW) . We thank Claire Levine for assistance with this manuscript.
PY - 2010/10
Y1 - 2010/10
N2 - Intracerebral hemorrhage (ICH) can cause secondary brain damage through inflammation-related pathways. Thrombin and one of its receptors, protease activated receptor-1 (PAR-1); matrix metalloproteinase (MMP)-9; and aquaporin (AQP)-4 are stroke-related inflammatory mediators that have been implicated in ICH pathology. To further characterize the inflammatory response after ICH, we studied the temporal profile of the expression of these inflammatory mediators and assessed their potential correlation with brain edema formation after brain hemorrhage in rats. ICH was modeled by infusing autologous blood into the striatum. Then mRNA and protein expression was assessed over the course of 5 days. We found that the mRNA and/or protein expression of thrombin, PAR-1, AQP-4, and MMP-9 was upregulated between 2 h and 5 days after ICH. Each reached a maximal level at day 2, except for AQP-4 protein, which peaked at day 5. Brain water content after ICH presented a similar trend; it was increased at 2 h, peaked at day 2, and then decreased but remained elevated at day 5. Our data provide novel evidence that upregulation of these selected inflammatory mediators occurs very early and persists for several days after ICH, and that temporal patterns of expression of thrombin and AQP-4 are associated with brain edema formation. These findings have important implications for efforts to reduce secondary brain damage after ICH.
AB - Intracerebral hemorrhage (ICH) can cause secondary brain damage through inflammation-related pathways. Thrombin and one of its receptors, protease activated receptor-1 (PAR-1); matrix metalloproteinase (MMP)-9; and aquaporin (AQP)-4 are stroke-related inflammatory mediators that have been implicated in ICH pathology. To further characterize the inflammatory response after ICH, we studied the temporal profile of the expression of these inflammatory mediators and assessed their potential correlation with brain edema formation after brain hemorrhage in rats. ICH was modeled by infusing autologous blood into the striatum. Then mRNA and protein expression was assessed over the course of 5 days. We found that the mRNA and/or protein expression of thrombin, PAR-1, AQP-4, and MMP-9 was upregulated between 2 h and 5 days after ICH. Each reached a maximal level at day 2, except for AQP-4 protein, which peaked at day 5. Brain water content after ICH presented a similar trend; it was increased at 2 h, peaked at day 2, and then decreased but remained elevated at day 5. Our data provide novel evidence that upregulation of these selected inflammatory mediators occurs very early and persists for several days after ICH, and that temporal patterns of expression of thrombin and AQP-4 are associated with brain edema formation. These findings have important implications for efforts to reduce secondary brain damage after ICH.
KW - Aquaporin-4
KW - Blood
KW - Intracerebral hemorrhage
KW - MMP-9
KW - PAR-1
KW - Thrombin
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U2 - 10.1016/j.neuint.2010.06.002
DO - 10.1016/j.neuint.2010.06.002
M3 - Article
C2 - 20541575
AN - SCOPUS:77955096639
SN - 0197-0186
VL - 57
SP - 248
EP - 253
JO - Neurochemistry International
JF - Neurochemistry International
IS - 3
ER -