TY - JOUR
T1 - Induction of infarct tolerance by platelet-derived growth factor against temporary focal ischemia
AU - Sakata, M.
AU - Yanamoto, H.
AU - Hashimoto, N.
AU - Iihara, K.
AU - Tsukahara, T.
AU - Taniguchi, T.
AU - Kikuchi, H.
N1 - Funding Information:
We gratefully acknowledge the assistance of Dr. Masahiro Kojima, Miss Satomi Nakano, Miss Kumi Shinoki, Miss Megumi Toriyama to this study. This study was supported by Special Coordination Funds for Promoting Science and Technology from the Science and Technology Agency of Japan, and by grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 1998/2/16
Y1 - 1998/2/16
N2 - Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet- derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 μg in total), 7 days (2 μg or 4 μg in total), or 14 days (4 μg in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF- BB (4μg in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF- BB or saline. In the group receiving PDGF-BB (4μg in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF- BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF- BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.
AB - Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet- derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 μg in total), 7 days (2 μg or 4 μg in total), or 14 days (4 μg in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF- BB (4μg in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF- BB or saline. In the group receiving PDGF-BB (4μg in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF- BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF- BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.
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U2 - 10.1016/S0006-8993(97)01345-0
DO - 10.1016/S0006-8993(97)01345-0
M3 - Article
C2 - 9518639
AN - SCOPUS:0032536345
VL - 784
SP - 250
EP - 255
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -