J Korean Med Sci.  2007 Feb;22(1):122-126. 10.3346/jkms.2007.22.1.122.

Neuroprotective Effects of Growth Hormone Against Hypoxic-Ischemic Brain Injury in Neonatal Rats: 1H Magnetic Resonance Spectroscopic Study

• Han TR
• Chun MH
• Jang DH
• Kim KS
• Lim KH
• Cho HJ

• KMID: 1713250
• DOI: http://doi.org/10.3346/jkms.2007.22.1.122

Abstract

Using 1H-MRS, we evaluated the effects of growth hormone (GH) as a caspase inhibitor on hypoxic-ischemic injury in neonatal rat brains. The right common carotid arteries of rats were ligated, allowed to recover for 3 hr, and exposed to 8% oxygen for 2 hr. GH was given just prior to HI insult and animals were divided into four groups: control, intracerebroventricular (ICV), intracerebroventricular/intraperitoneal (ICV/IP), and intraperitoneal (IP). Localized in vivo 1H-MRS and TUNEL staining were performed 24 hr after HI injury. Lipid/N-acetyl aspartate (NAA) and lipid/creatine (Cr) ratios were used as apoptotic markers. Gross morphologic changes at 2 weeks were used to evaluate the effects of GH. The lipid/NAA ratio was lower in the ICV and ICV/IP groups than in the control, and the lipid/Cr ratio was lower in the ICV group than in the control. The number of TUNEL positive cells was decreased in the ICV and ICV/IP groups, and the degree of morphologic change indicative of brain injury was lower in the ICV group and somewhat lower in the ICV/IP group. The degree of morphologic change correlated with the lipid/NAA and lipid/Cr ratios. These findings suggest that GH exerts neuroprotective effects in cerebral hypoxicischemic injury.

Keyword

Magnetic Resonance Spectroscopy; Hypoxia-Ischemia Brain; Growth Hormone; Apoptosis; Caspase Inhibitors

MeSH Terms

Rats, Sprague-Dawley
Rats
Neuroprotective Agents/*therapeutic use
*Magnetic Resonance Spectroscopy
Lipids/analysis
Hypoxia-Ischemia, Brain/*drug therapy/metabolism
Growth Hormone/*therapeutic use
Creatinine/analysis
Aspartic Acid/analogs & derivatives/analysis
Animals, Newborn
Animals

Figure

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  Fig. 1 Lipid/NAA ratios among control and growth hormone pretreated groups. *p<0.05 compared with control. NAA, N-acetyl aspartate; ICV, intracerebroventricular; IP, intraperitoneal.

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  Fig. 2 Lipid/Cr ratios among control and growth hormone pretreated groups. *p<0.05 compared with control. Cr, Creatine; ICV, intracerebroventricular; IP, intraperitoneal.

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  Fig. 3 Hypoxic-ischemic injury in the right hemispheres of neonatal rat brains pretreated with growth hormone. There were many apoptotic cells in the control and IP groups, but fewer in the ICV and ICV+IP groups. ICV, intracerebroventricular; IP, intraperitoneal. TUNEL stain (×100).

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  Fig. 4 Morphologic scores among control and growth hormone pretreated groups. *p<0.05 compared with control. ICV, intracerebroventricular; IP, intraperitoneal.

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  Fig. 5 Correlations of Lipid/NAA (A) and Lipid/Cr (B) ratios with morphologic scores. NAA, N-acetyl aspartate; Cr, Creatine.

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