Effects of chronic clozapine administration on apolipoprotein D levels and on functional recovery following experimental stroke.

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Abstract

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. 10mg/kg body weight) or saline for 8 or 28days starting on the second day after MCAO. ApoD levels increased by 35% in the peri-infarct area after 10 and 30days 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 7d, 14d, 21d, and 28days after pMCAO. Functional outcome and the infarct size were similar in rats subjected to transient MCAO and injected with Clozapine (i.p. 10mg/kg body weight) or saline for 26days 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.

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  • Neurosciences
Original languageEnglish
Pages (from-to)152-163
JournalBrain Research
Volume1321
StatePublished - 2010
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Laboratory for Experimental Brain Research (013041000)