Hematopoietic growth factors pass through the blood-brain barrier in intact rats.
We have previously demonstrated that receptors for hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are expressed in the neurons and the neural progenitor cells (NPCs) of the adult rat brain, and that systemic administration of SCF and G-CSF in the first week after induction of cortical brain ischemia (3 h-7 days post-ischemia) significantly improves functional outcome, augments NPC proliferation, and reduces infarct volume in rats. The purpose of the present study is to determine whether SCF and G-CSF pass through the blood-brain barrier (BBB) in intact rats. The growth factors were labeled with iodine (I(125)), a radioactive compound. I(125)-SCF and I(125)-G-CSF were intravenously administered and the concentrations of I(125)-SCF and I(125)-G-CSF in the blood plasma and the brain were determined at 10, 30, 60, and 120 min after injection. We observed that both SCF and G-CSF were slowly and continuously transported from the blood stream to the brain in the same rate. In addition, both immunofluorescent staining and Western blots showed that receptors for SCF and G-CSF were expressed in the capillaries of the adult rat brain, suggesting that SCF and G-CSF entry to the brain may be mediated via receptor-mediated transport, one of the endogenous transports in the BBB. These data indicate that both SCF and G-CSF were able to pass through the BBB in intact animals. This observation will help in further exploring the physiological role of peripheral SCF and G-CSF in the brain and therapeutic possibility to chronic stroke.
Zhao
Li-Ru
LR
Department of Neurology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. lzhao@lsuhsc.edu
Navalitloha
Yot
Y
Singhal
Seema
S
Mehta
Jayesh
J
Piao
Chun-Shu
CS
Guo
Wen-Ping
WP
Kessler
John A
JA
Groothuis
Dennis R
DR
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D019089:Stem Cell Factor / Q000378:metabolism*; D013997:Time Factors
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D007455:Iodine