Vascular recovery promoted by atorvastatin and simvastatin after experimental intracerebral hemorrhage: magnetic resonance imaging and histological study.
OBJECTIVE
Longitudinal multiparametric MR imaging and histological studies were performed on simvastatin- or atorvastatin-treated rats to evaluate vascular repair mechanisms after experimental intracerebral hemorrhage (ICH).


METHODS
Primary ICH was induced in adult Wistar rats by direct infusion of 100 μl of autologous blood into the striatal region adjacent to the subventricular zone. Atorvastatin (2 mg/kg), simvastatin (2 mg/kg), or phosphate-buffered saline was given orally at 24 hours post-ICH and continued daily for 7 days. The temporal evolution of ICH in each group was assessed by MR imaging measurements of T2, T1(sat), and cerebral blood flow in brain areas corresponding to the bulk of the hemorrhage (core) and edematous border (rim). Rats were killed after the final MR imaging examination at 28 days, and histological studies were performed. A small group of sham-operated animals was also studied. Neurobehavioral testing was performed in all animals. Analysis of variance methods were used to compare results from the treatment and control groups, with significance inferred at p ≤ 0.05.


RESULTS
Using histological indices, animals treated with simvastatin and atorvastatin had significantly increased angiogenesis and synaptogenesis in the hematoma rim compared with the control group (p ≤ 0.05). The statin-treated animals exhibited significantly increased cerebral blood flow in the hematoma rim at 4 weeks, while blood-brain barrier permeability (T1(sat)) and edema (T2) in the corresponding regions were reduced. Both statin-treated groups showed significant neurological improvement from 2 weeks post-ICH onward.


CONCLUSIONS
The results of the present study demonstrate that simvastatin and atorvastatin significantly improve the recovery of rats from ICH, possibly via angiogenesis and synaptic plasticity. In addition, in vivo multiparametric MR imaging measurements over time can be effectively applied to the experimental ICH model for longitudinal assessment of the therapeutic intervention.
Yang
Dongmei
D
Departments of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Knight
Robert A
RA
Han
Yuxia
Y
Karki
Kishor
K
Zhang
Jianfeng
J
Ding
Christopher
C
Chopp
Michael
M
Seyfried
Donald M
DM
D000818:Animals; D000069059:Atorvastatin; D001812:Blood-Brain Barrier / Q000502:physiology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000627:therapeutic use*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin