Influence of age on the response to fibroblast growth factor-2 treatment in a rat model of stroke.
Basic fibroblast growth factor (FGF-2) has been reported to protect against ischemic injury in the brains of young adult rodents. However, little is known about whether FGF-2 retains this capability in the aged ischemic brain. Since stroke in human is much more common in older people than among younger adults, to address this question is clinically important. In this study, aged (24-month-old) rats were treated with intracerebroventricular infusion of FGF-2 or vehicle for 3 days, beginning 48 h before (pre-ischemia), 24 h after (early post-ischemia), or 96 h after (late post-ischemia) 60 min of middle cerebral artery occlusion, and were killed 10 days after ischemia. Aged rats given FGF-2 pre-ischemia showed better symmetry of movement and forepaw outstretching, and reduced infarct volumes, compared to rats treated with vehicle, but no significant improvement was found in aged rats given FGF-2 after focal ischemia. In contrast, young adult (3-month-old) rats treated with FGF-2 for 3 days beginning 24 h post-ischemia showed significant neurobehavioral improvement and better histological outcome. In addition, we also found that newborn neurons in the rostral subventricular zone (SVZ) were increased in aged rats treated with FGF-2 prior to ischemia. However, unlike in young adult ischemic rats, only a few of newly generated cells migrated into the damaged region in aged brain after focal ischemia. These findings point to differences in the response of aged versus young adult rats to FGF-2 in cerebral ischemia, and suggest that such differences need to be considered in the development of neuroprotective agents for stroke.
Won
Seok Joon
SJ
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Xie
Lin
L
Kim
Sun Hee
SH
Tang
Huidong
H
Wang
Yaoming
Y
Mao
Xiaoou
X
Banwait
Surita
S
Jin
Kunlin
K
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000187:drug effects*; D020521:Stroke / Q000188:drug therapy*
D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2