TY - GEN
T1 - The dual role of src kinases in intracerebral hemorrhage
AU - Liu, Da
AU - Sharp, Frank R
PY - 2011
Y1 - 2011
N2 - Src kinase signaling has been implicated in multiple mechanisms of intracerebral hemorrhage (ICH). These include (1) thrombin-mediated mitogenic stress, (2) excitatory amino acid (AA)-mediated excitatory toxicity, (3) vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)-mediated changes of vascular permeability, (4) cytokines-mediated inflammatory responses, and (5) others. These work together after ICH, causing brain injuries in the acute stage and self-repair in the recovery stage. We found that acute administration of the Src inhibitor, PP2, blocks the blood-brain barrier (BBB) breakdown and brain edema that occurs after ICH. However, delayed and chronic administration of PP2 prevents the BBB repair and edema resolution after ICH. These results led us to suggest that the two contradictory findings share the same principles at least in part via activation of Src kinases in acute or recovery stages after ICH. Acute Src kinase activation after ICH leads to BBB damage, and chronic Src kinase activation after ICH leads to BBB repair.
AB - Src kinase signaling has been implicated in multiple mechanisms of intracerebral hemorrhage (ICH). These include (1) thrombin-mediated mitogenic stress, (2) excitatory amino acid (AA)-mediated excitatory toxicity, (3) vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)-mediated changes of vascular permeability, (4) cytokines-mediated inflammatory responses, and (5) others. These work together after ICH, causing brain injuries in the acute stage and self-repair in the recovery stage. We found that acute administration of the Src inhibitor, PP2, blocks the blood-brain barrier (BBB) breakdown and brain edema that occurs after ICH. However, delayed and chronic administration of PP2 prevents the BBB repair and edema resolution after ICH. These results led us to suggest that the two contradictory findings share the same principles at least in part via activation of Src kinases in acute or recovery stages after ICH. Acute Src kinase activation after ICH leads to BBB damage, and chronic Src kinase activation after ICH leads to BBB repair.
KW - Blood-brain barrier
KW - Intracerebral hemorrhage
KW - Neurogenesis
KW - Neuronal apoptosis
KW - Src kinases
KW - Vasogenic edema
UR - http://www.scopus.com/inward/record.url?scp=79960689272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960689272&partnerID=8YFLogxK
U2 - 10.1007/978-3-7091-0693-8_13
DO - 10.1007/978-3-7091-0693-8_13
M3 - Conference contribution
C2 - 21725735
AN - SCOPUS:79960689272
SN - 9783709106921
T3 - Acta Neurochirurgica, Supplementum
SP - 77
EP - 81
BT - Acta Neurochirurgica, Supplementum
ER -