Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain.
Changes in expression of neurorepair and neuroregenerative factors were examined after transient cerebral ischemia in relation to the effects of tissue plasminogen activator (tPA) and the free radical scavenger edaravone. Physiological saline or edaravone was injected twice during 90 min of transient middle cerebral artery occlusion (tMCAO) in rats, followed by the same saline or tPA at reperfusion. Sizes of the infarct and protein factors relating to neurorepair and neuroregeneration were examined at 4d after tMCAO. The protein factors examined were: a chondroitin sulfate proteoglycan neurocan, semaphorin type 3A (Sema3A), a myelin-associated glycoprotein receptor (Nogo receptor, Nogo-R), a synaptic regenerative factor (growth associated protein-43, GAP43), and a chemotropic factor netrin receptor (deleted in colorectal cancer, DCC). Two groups treated by edaravone only or edaravone plus tPA showed a reduction in infarct volume compared to the two groups treated by vehicle only or vehicle plus tPA. Immunohistochemistry and western blot analyses indicated that protein expression of neurocan, Sema3A, Nogo-R, GAP43, and DCC was decreased with tPA, but recovered with edaravone. Additive edaravone prevented the reductions of these five proteins induced by tPA. The present study demonstrates for the first time that exogenous tPA reduced protein factors involved in inhibiting and promoting axonal growth, but that edaravone ameliorated such damage in brain repair after acute ischemia.
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Kentaro
K
Deguchi
Kazunori
K
Miyazaki
Fengfeng
F
Tian
Ning
N
Liu
Wentao
W
Liu
Hiromi
H
Kawai
Yosiho
Y
Omote
Syoichiro
S
Kono
Taijun
T
Yunoki
Shoko
S
Deguchi
Koji
K
Abe
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001921:Brain / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis; D000077553:Edaravone; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D019922:GAP-43 Protein / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000032:analysis; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D009185:Myelin Proteins / Q000032:analysis; D000075386:Netrin Receptors; D058580:Neurocan; D000070816:Nogo Receptor 1; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism; D015424:Reperfusion; D040121:Semaphorin-3A / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*
D011508:Chondroitin Sulfate Proteoglycans; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D019922:GAP-43 Protein; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C539091:Ncan protein, rat; D000075386:Netrin Receptors; D058580:Neurocan; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D010959:Tissue Plasminogen Activator; D000077553:Edaravone; D000983:Antipyrine