Abstract
Purpose:The first 3 weeks of life is the peak time of oligodendrocytes development and also
the critical period of cholesterol increasing dramatically in central nervous system
in rats. Neonatal hypoxia-ischemia (HI) brain damage happening in this period may
disturb the brain cholesterol balance as well as white matter development.
Materials and Methods:To test this hypothesis, postnatal day 7 (P7) Sprague-Dawley rats were subjected to
HI insult. Cholesterol concentrations from brain and plasma were measured. White matter
integrity was evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining
and electron microscopy. Brain TNF-α and IL-6 levels were also measured.
Results:HI-induced brain cholesterol, but not the plasma cholesterol, levels decreased significantly
during the first three days after HI compared with naïve and sham operated rats (p<0.05).
Obvious hypomyelination was indicated by marked reductions in MBP immunostaining on
both P10 and P14 (p<0.01) and less and thinner myelinated axons were detected on P21
by electron microscopy observation. High expressions of brain TNF-α and IL-6 12 h
after HI (p<0.05) were also observed.
Discussion:The present work provides evidence that HI insult destroyed brain cholesterol homeostasis,
which might be important in the molecular pathology of hypoxic-ischemic white matter
injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol
unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol
balance may be effective for the recovery of white matter function.
Key words
hypoxia-ischemia brain damage - brain cholesterol - white matter damage - oligodendrocytes
- cytokines - neonatal rats
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Correspondence
A. P. LiMD
Department of Physiology
Dalian Medical University
No.9 West Section
Lushun South Road
Dalian
People's Republic of China
Telefon: +86/411/86 11 02 88
eMail: li.ap@126.com
