TY - CHAP
T1 - Erythropoietin attenuates intracerebral hemorrhage by diminishing matrix metalloproteinases and maintaining blood-brain barrier integrity in mice
AU - Li, Y.
AU - Ogle, M. E.
AU - Wallace IV, G. C.
AU - Lu, Z. Y.
AU - Yu, S. P.
AU - Wei, L.
PY - 2008
Y1 - 2008
N2 - The protective mechanism of recombinant human erythropoietin (rhEPO) on blood-brain barrier (BBB) after brain injury is associated with the attenuation of neuro-inflammation. We hypothesize that rhEPO treatment after intracerebral hemorrhage (ICH) modulates matrix metal-loproteinase (MMP) activity, maintains BBB integrity, and reduces BBB breakdown-associated inflammation. Adult male 129S2/sv mice were subjected to autologous whole blood-induced ICH. rhEPO or saline was administered intraperitoneally immediately after surgery and for 3 more days until day of sacrifice. BBB permeability was measured by Evans blue leakage, and edema was assessed by brain water content. Immunofluorescence and Western blotting were performed to detect expression of tight junction marker oc-cludin, type IV collagen, MMPs, tissue inhibitor of metalloproteinase (TIMP), and glial fibrillary acidic protein. rhEPO prevented Evans blue leakage, reduced brain edema, and preserved expression of occludin and collagen IV rhEPO treatment decreased MMP-2 expression, increased TIMP-2 expression, and reduced the number of reactive astrocytes in the brain compared to saline control. We conclude that rhEPO reduces MMP activity, BBB disruption, and the glial cell inflammatory reaction 3 days after ICH. Our study provides additional evidence for the mechanism of rhEPO's neurovascular protective effects and a potential clinical application in the treatment of ICH.
AB - The protective mechanism of recombinant human erythropoietin (rhEPO) on blood-brain barrier (BBB) after brain injury is associated with the attenuation of neuro-inflammation. We hypothesize that rhEPO treatment after intracerebral hemorrhage (ICH) modulates matrix metal-loproteinase (MMP) activity, maintains BBB integrity, and reduces BBB breakdown-associated inflammation. Adult male 129S2/sv mice were subjected to autologous whole blood-induced ICH. rhEPO or saline was administered intraperitoneally immediately after surgery and for 3 more days until day of sacrifice. BBB permeability was measured by Evans blue leakage, and edema was assessed by brain water content. Immunofluorescence and Western blotting were performed to detect expression of tight junction marker oc-cludin, type IV collagen, MMPs, tissue inhibitor of metalloproteinase (TIMP), and glial fibrillary acidic protein. rhEPO prevented Evans blue leakage, reduced brain edema, and preserved expression of occludin and collagen IV rhEPO treatment decreased MMP-2 expression, increased TIMP-2 expression, and reduced the number of reactive astrocytes in the brain compared to saline control. We conclude that rhEPO reduces MMP activity, BBB disruption, and the glial cell inflammatory reaction 3 days after ICH. Our study provides additional evidence for the mechanism of rhEPO's neurovascular protective effects and a potential clinical application in the treatment of ICH.
KW - Intracerebral hemorrhage
KW - anti-inflammatory
KW - blood-brain barrier
KW - matrix metalloproteinase
KW - neurovascular protection
KW - recombinant human erythropoietin
KW - tissue inhibitor of metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=85052609749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052609749&partnerID=8YFLogxK
U2 - 10.1007/978-3-211-09469-3_22
DO - 10.1007/978-3-211-09469-3_22
M3 - Chapter
C2 - 19066093
AN - SCOPUS:85052609749
SN - 9783211094686
T3 - Acta Neurochirurgica, Supplementum
SP - 105
EP - 112
BT - Cerebral Hemorrhage
PB - Springer-Verlag Wien
ER -