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 microg in total), 7 days (2 microgram or 4 microgram in total), or 14 days (4 microgram in total) pre-
ischemia and 2 days post-
ischemia. In an additional group,
PDGF-BB (4 microgram 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 (4 microgram 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.