TITLE:
Statins Protect the Blood Brain Barrier Acutely after Experimental Intracerebral Hemorrhage
AUTHORS:
Dongmei Yang, Robert A. Knight, Yuxia Han, Kishor Karki, Jianfeng Zhang, Michael Chopp, Donald M. Seyfried
KEYWORDS:
Intracerebral Hemorrhage; Atorvastatin; Occludin; Simvastatin; Blood Brain Barrier
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.3 No.1,
February
27,
2013
ABSTRACT: Objectives: The goal of this study was to measure the impact of simvastatin and
atorvastatin treatment on blood brain barrier (BBB) integrity after
experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was induced in
27 male Wistar rats by stereotactic injection of100mL
of autologous blood into the striatum. Rats were divided into three groups (n = 9/group): 1) oral
treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin,
or 3) phosphate buffered saline
daily starting 24-hours post-ICH and continuing daily for the next 3 days. On
the fourth day, the animals underwent magnetic resonance imaging (MRI) for
measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed
and immunohistology or Western blotting was performed. Results: MRI data for animals receiving simvastatin treatment
showed significantly reduced BBB dysfunction and improved CBF in the ICH rim
compared to controls (P 0.05) 4 days after ICH. Simvastatin also significantly reduced
edema (T2) in the rim at 4 days after ICH (P 0.05). Both statin-treated groups demonstrated increased occludin and
endothelial barrier antigen levels within the vessel walls, indicating better preservation
of BBB function (P 0.05) and increased number of blood vessels (P 0.05). Conclusions: Simvastatin treatment
administered acutely after ICH protects BBB integrity as measured by MRI and
correlative immunohistochemistry. There was also evidence of improved CBF and
reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend
by MRI measurement.