Cilostazol protects against brain white matter damage and cognitive impairment in a rat model of chronic cerebral hypoperfusion

Stroke; a Journal of Cerebral Circulation
Terubumi WatanabeTakao Urabe

Abstract

White matter lesions contribute to cognitive impairment in poststroke patients. The present study was designed to assess the neuroprotective mechanisms of cilostazol, a potent inhibitor of type III phosphodiesterase, through signaling pathways that lead to activation of transcription factor cAMP-responsive element binding protein (CREB) phosphorylation using rat chronic cerebral hypoperfusion model. Rats underwent bilateral common carotid artery ligation. They were divided into the cilostazol group (n=80) and the vehicle (control) group (n=80). Performance at the Morris water maze task and immunohistochemistry for 4-hydroxy-2-nonenal (HNE), glutathione-S-transferase-pi (GST-pi), ionized calcium-binding adaptor molecule 1, phosphorylated CREB (p-CREB), Bcl-2, and cyclooxygenase-2 (COX-2) were analyzed at baseline and at 3, 7, 14, 21, and 28 days after hypoperfusion. Cilostazol significantly improved spatial learning memory (6.8+/-2.3 seconds; P<0.05) at 7 days after hypoperfusion. Cilostazol markedly suppressed accumulation of HNE-modified protein and loss of GST-pi-positive oligodendrocytes in the cerebral white matter during the early period after hypoperfusion (P<0.05). Cilostazol upregulated p-CREB and Bcl-2 (P<0.05), increa...Continue Reading

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Citations

Dec 12, 2012·Cellular and Molecular Neurobiology·Shoji HoraiMasami Niwa
Nov 21, 2009·Neuroscience Bulletin·Jian-Jun GuoHai-Feng Xie
Jan 1, 2010·Anesthesia and Analgesia·Naoko OkayamaYuichi Kanmura
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