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

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 hypoxic-ischemic injury.

GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

“…These data provide a basis for understanding previous studies of neural regeneration by GH following hypoxic-ischemic injury [38]–[40]. We postulate that in addition to being neuroprotective, as suggested by Han and colleagues [41], GH can induce the activation of the endogenous NPC pool in the injured, aged brain. Our observation that NPC numbers could not be recovered with exercise in irradiated animals infused with a GH antagonist demonstrates that, in the SVZ, GH-induced NPC activation and exercise-induced NPC activation are linked.…”

The effect of recombinant human growth hormone and insulin-like growth factor-1 on the mitochondrial function and viability of peripheral blood mononuclear cells in vitro

“…Neither rhGH nor rIGF-1, at any treatment concentration, was found to have a significant effect on mtPTP activity or the percentage of cells undergoing apoptosis, which is not surprising given that both hormones failed to induce an increase in the level of mitochondrial oxidative stress, even at supra-physiological concentrations. Indeed both hormones have been shown to act as "survival agents", preventing the onset of apoptosis in specific cell types (Han et al 2007;Kang et al 2003;Mitsunaka et al 2001;Yamamura et al 2001). Mitsunaka et al (2001) initiated intracellular death signalling pathways via activation of plasma membrane bound Fas receptors in IM-9 lymphocytes and Han et al (2007) induced hypoxic-ischemic injury in neonatal rat brain neurons.…”

“…Indeed both hormones have been shown to act as "survival agents", preventing the onset of apoptosis in specific cell types (Han et al 2007;Kang et al 2003;Mitsunaka et al 2001;Yamamura et al 2001). Mitsunaka et al (2001) initiated intracellular death signalling pathways via activation of plasma membrane bound Fas receptors in IM-9 lymphocytes and Han et al (2007) induced hypoxic-ischemic injury in neonatal rat brain neurons. Both authors attributed the ability of GH to prevent apoptosis to an inhibition of caspase-dependent cell death pathways.…”

Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury Evaluated with Magnetic Resonance Spectroscopy

“…Specifically, the Lip peak at 1.3 ppm has been correlated with brain cell death and a loss of mitochondrial membrane potential 24 h after HI in neonatal rats [68] . Hence, the antiapoptotic properties of intracerebroventricular treatment with growth hormone, a caspase inhibitor, prior to a hypoxic-ischemic insult in neonatal rats, were reflected in Lip 1.3 ppm /NAA and Lip 1.3 ppm /Cr ratios that were lower than in the control group at 24 h after HI [69] . Another study by the same research group found lower Lip 0.9 ppm /Cr and Lip 1.3 ppm /Cr levels 7 days after HI with daily lithium treatment.…”