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(Stroke. 2009;40:3384.)
© 2009 American Heart Association, Inc.

Original Contributions

Simvastatin and Atorvastatin Improve Neurological Outcome After Experimental Intracerebral Hemorrhage

Kishor Karki, PhD; Robert A. Knight, PhD; Yuxia Han, BS; Dongmei Yang, MD; Jianfeng Zhang, MS; Karyn A. Ledbetter, BS; Michael Chopp, PhD Donald M. Seyfried, MD

From the Departments of Neurology (K.K., R.A.K., K.A.L., M.C.) and Neurosurgery (Y.H., D.Y., J.Z., D.M.S.), Henry Ford Hospital, Detroit, Mich; and the Department of Physics (K.K., R.A.K., M.C.), Oakland University, Rochester, Mich.

Correspondence to Dr Donald M. Seyfried, Department of Neurosurgery, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202. E-mail nsdos{at}neuro.hfh.edu

Background and Purpose— This study investigates the effects of statin treatment on experimental intracerebral hemorrhage (ICH) using behavioral, histological, and MRI measures of recovery.

Methods— Primary ICH was induced in rats. Simvastatin (2 mg/kg), atorvastatin (2 mg/kg), or phosphate-buffered saline (n=6 per group) was given daily for 1 week. MRI studies were performed 2 to 3 days before ICH, and at 1 to 2 hours and 1, 2, 7, 14, and 28 days after ICH. The ICH evolution was assessed via hematoma volume measurements using susceptibility-weighted imaging (SWI) and tissue loss using T₂ maps and hematoxylin and eosin (H&E) histology. Neurobehavioral tests were done before ICH and at various time points post-ICH. Additional histological measures were performed with doublecortin neuronal nuclei and bromodeoxyuridine stainings.

Results— Initial ICH volumes determined by SWI were similar across all groups. Simvastatin significantly reduced hematoma volume at 4 weeks (P=0.002 versus control with acute volumes as baseline), whereas that for atorvastatin was marginal (P=0.09). MRI estimates of tissue loss (% of contralateral hemisphere) for treated rats were significantly lower (P=0.0003 and 0.001, respectively) than for control at 4 weeks. Similar results were obtained for H&E histology (P=0.0003 and 0.02, respectively). Tissue loss estimates between MRI and histology were well correlated (R²=0.764, P<0.0001). Significant improvement in neurological function was seen 2 to 4 weeks post-ICH with increased neurogenesis observed.

Conclusions— Simvastatin and atorvastatin significantly improved neurological recovery, decreased tissue loss, and increased neurogenesis when administered for 1 week after ICH.

Key Words: hematoma • statin • MRI • SWI • rat