From the Department of Neurology, Henry Ford Health Sciences Center,
Detroit, Mich (Y.L., N.J., C.P., M.C.), and Department of Physics, Oakland
University, Rochester, Mich (C.P.).
Correspondence to Michael Chopp, PhD, Henry Ford Hospital, Neurology Department, 2799 W Grand Blvd, Detroit, MI 48202. E-mail chopp{at}neuro.hfh.edu
Background and Purpose—An
objective of therapeutic intervention after cerebral ischemia
is to promote improved functional outcome. Improved outcome may be
associated with a reduction of the volume of cerebral infarction and
the promotion of cerebral plasticity. In the developing brain, neuronal
growth is concomitant with expression of particular proteins, including
microtubule-associated protein 2 (MAP-2), growth-associated protein 43
(GAP-43), and cyclin D1. In the present study we measured the
expression of select proteins associated with neurite damage and
plasticity (MAP-2 and GAP-43) as well as cell cycle (cyclin D1) after
induction of focal cerebral ischemia in the rat.
Methods—Brains from rats (n=28) subjected to 2 hours of middle
cerebral artery occlusion and 6 hours, 12 hours, and 2, 7, 14, 21, and
28 days (n=4 per time point) of reperfusion and control sham-operated
(n=3) and normal (n=2) rats were processed by immunohistochemistry with
antibodies raised against MAP-2, GAP-43, and cyclin D1. Double staining
of these proteins for cellular colocalization was also performed.
Results—Loss of immunoreactivity of both MAP-2 and GAP-43 was
observed in most damaged neurons in the ischemic core. In
contrast, MAP-2, GAP-43, and cyclin D1 were selectively increased in
morphologically intact or altered neurons localized to the
ischemic core at an early stage (eg, 6 hours) of reperfusion
and in the boundary zone to the ischemic core (penumbra) during
longer reperfusion times.
Conclusions—The selective expressions of the neuronal structural
proteins (MAP-2 in dendrites and GAP-43 in axons) and the cyclin D1
cell cycle protein in neurons observed in the boundary zone to the
ischemic core are suggestive of compensatory and repair
mechanisms in ischemia-damaged neurons after transient focal
cerebral ischemia.
Laboratory for Experimental Neurology Wallenberg
Neuroscience
Center Lund University Hospital Lund, Sweden
© 1998 American Heart Association, Inc.
Original Contributions
Neuronal Damage and Plasticity Identified by Microtubule-Associated Protein 2, Growth-Associated Protein 43, and Cyclin D1 Immunoreactivity After Focal Cerebral Ischemia in Rats
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