Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats.
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.
De Ryck
M
M
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
Van Reempts
J
J
Borgers
M
M
Wauquier
A
A
Janssen
P A
PA
D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D005444:Flunarizine / Q000627:therapeutic use*; D006614:Hindlimb / Q000294:innervation; D008027:Light; D008297:Male; D009044:Motor Cortex / Q000187:drug effects; D011434:Proprioception / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012395:Rose Bengal; D013997:Time Factors; D014110:Touch / Q000502:physiology
D012395:Rose Bengal; D005444:Flunarizine