C-reactive protein expression in a rodent model of chronic cerebral hypoperfusion

Abstract White matter lesions (WML) are a clinically significant, common feature of the aging brain and have been associated with cognitive decline and depression. They are a manifestation of cerebral small vessel disease, which is associated with the progression of vascular dementia. Recent research has been focused on identifying biomarkers which may have a correlation with WML. Previous population based studies have indicated a relation between the serum level of the acute phase protein, C-reactive protein (CRP), and WML. However no previous studies have demonstrated its expression and relation to WML in brain tissue itself. Here we use the rodent model of permanent bilateral common carotid artery ligation (BCCAL) to assess CRP expression during chronic cerebral hypoperfusion (CCH). Our results show that CRP is up-regulated at the mRNA and protein levels in brain tissue from BCCAL animals. The expression of CRP mRNA was upregulated on day 3 following surgery. Because previous studies, as well as the present study, have shown that microglial activity is prominent after the third day of CCH, we sought to determine the role of microglia in CRP expression. Results indicate that cultured microglia express mRNA and protein for CRP and this expression is increased when cells are treated with interleukin-1β (IL-1β), interleukin-6 (IL-6) or a combination of the two.. This finding could indicate a possible role for CRP in the progression of small vessel disease in the brain and provide a therapeutic target.