Simvastatin attenuates hypomyelination induced by hypoxia-ischemia in neonatal rats.
OBJECTIVE
Simvastatin, the most widely used cholesterol-lowering drug, has been reported to protect the adult brain from ischemia. Nevertheless, little is known about its action on developing brain after stroke. Although a few reports have found recently that simvastatin displays anti-inflammation and anti-apoptosis properties and improves the cognitive and morphological consequences in the neonatal rats after hypoxia-ischemia (HI) damage, to our best knowledge, there has been no study of the effect of it on myelin formation after neonatal brain damage. Therefore, we investigated whether simvastatin could promote the myelination of oligodendrocytes in the neonatal rats after HI and explored the possible role of microglial responses in this process.


METHODS
Postnatal day 7 Sprague-Dawley rats were subjected to HI. White matter integrity and myelination were evaluated by the densitometry of myelin basic protein (MBP) immunostaining. OX-42 immunoreactivity and nissl staining were used for identifying microglial responses and the structure changes of white matter and adjacent gray matter after HI. Simvastatin was administrated prophylactically to rats.


RESULTS
HI induced serious hypomyelination especially in external and internal capsules 3 and 7 days after HI, accompanying with microglial activation remarkably. Simvastatin treatment greatly increased the densities of MBP immunostaining, inhibited microglial activation and reduced the numbers of pyknotic cells and neuronal loss.


CONCLUSIONS
The present study shows that simvastatin treatment in neonatal rats attenuates HI-induced developing oligodendrocytes injury and hypomyelination. Its anti-inflammatory properties via suppression of microglial activation are likely to contribute to this action. It provides experimental evidence to support the neuroprotective effects of statins in neonatal ischemic stroke.
Li
Aiping
A
Department of Physiology, Dalian Medical University, China. li.ap@126.com
Lv
Shuhong
S
Yu
Zhe
Z
Zhang
Yumei
Y
Ma
Hui
H
Zhao
Hui
H
Piao
Hua
H
Li
Shao
S
Zhang
Nannan
N
Sun
Changkai
C
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
D039481:CD11b Antigen; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004676:Myelin Basic Protein; D019821:Simvastatin