Stroke, Vol 20, 1383-1390, Copyright © 1989 by American Heart Association
M De Ryck, J Van Reempts, M Borgers, A Wauquier and PA Janssen
We produced unilateral photochemical infarcts in the hindlimb sensorimotor
neocortex of 186 rats by intravenous injection of the fluorescein
derivative rose bengal and focal illumination of the intact skull surface.
Infarcted rats showed specific, long-lasting deficits in tactile and
proprioceptive placing reactions of the contralateral limbs, mostly the
hindlimb. Placing deficits were most prominent during transition to
immobility and/or when independent limb movements were required.
Administration of flunarizine, a Class IV calcium antagonist, 30 minutes
after infarction resulted in marked sparing of sensorimotor function in 30
rats. In contrast to 20 vehicle-treated rats, which remained deficient for
at least 21 days, 15 (75%) of the rats treated with 1.25 mg/kg i.v.
flunarizine showed normal placing on Day 1 after infarction, whereas the
remaining five (25%) recovered within 5 days. Oral treatment of 10 rats
with 40 mg/kg flunarizine was also effective. Neocortical infarct volume
and thalamic gliosis, assessed 21 days after infarction, did not differ
between 30 flunarizine- and 30 vehicle- treated rats. However, when
4-hour-old infarcts were measured in 16 rats, posttreatment with
intravenous flunarizine reduced infarct size by 31%. In combination with
appropriate behavioral analyses, photochemical thrombosis may constitute a
relevant stroke model, in which flunarizine preserved behavioral function
during a critical period, corresponding to the spread of ischemic damage.
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Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
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