Elevated brain levels of
apolipoprotein D (ApoD) correlate with improved neurological recovery after experimental
stroke. Hence, a pharmacological induction of ApoD in the postischemic brain could be beneficial for recovery after
stroke. Here we investigated the effect of
Clozapine, a compound that increases the expression of ApoD, in two rat models of experimental
stroke. Rats were subjected to permanent occlusion of the middle cerebral artery (pMCAO) and treated with
Clozapine (i.p. 10 mg/kg
body weight) or saline for 8 or 28 days starting on the second day after MCAO. ApoD levels increased by 35% in the peri-
infarct area after 10 and 30 days after pMCAO, mainly in neuron-specific
nuclear protein (NeuN) positive neurons and
glial fibrillary acidic protein (GFAP) positive astrocytes.
Clozapine did not affect the neurological deficit assessed by the rotating pole test and a grip strength test at 7 days, 14 days, 21 days, and 28 days after pMCAO. Functional outcome and the
infarct size were similar in rats subjected to transient MCAO and injected with
Clozapine (i.p. 10 mg/kg
body weight) or saline for 26 days starting on the second day after tMCAO. We conclude that
Clozapine affects cellular processes involved in peri-
infarct tissue reorganization, but does not affect functional recovery after MCAO.