Quantitative Immunohistochemical Analysis of Nitric Oxide Synthases and Apoptosis Regulator Proteins in the Fetal Rat Brain Following Maternal Uterine Artery Ligation

Abstract

The purpose of this study was to determine the relation between nitric oxide synthases (calcium-independent iNOS and calcium-dependent eNOS) and apoptosis regulator proteins (anti-apoptotic Bcl-2, pro-apoptotic p53) of fetal rat brain in experimental intrauterine growth retardation (IUGR) model via quantitative immunohistochemistry. Cortical zone of parietal cerebral cortex and ventricular zone of third ventricle were studied following bilateral uterine artery ligation on gestational day 18. Significant increase in iNOS immunoreactivity was determined in parietal cerebral cortex and ventricular zones as eNOS immunoreactivity increased in ventricular zone of IUGR group. Bcl-2 expression was significantly decreased in ventricular zone; whereas cortical zone of IUGR group expressed p53 immunoreactivity.

N-Acetylcysteine Amide Protects Renal Proximal Tubular Epithelial Cells against Iohexol-Induced Apoptosis by Blocking p38 MAPK and iNOS Signaling

“…Several studies reported that apoptosis mediated by iNOS activation could be accompanied by eNOS depression [28] or activation [31]. On the contrary, we found that eNOS protein expression was unchanged 2 h after IH exposure.…”

Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review

“…Bcl‐2 is an important anti‐apoptotic protein, while p53 is an pro‐apoptotic protein (Table ) . Studies of rats with placental insufficiency at birth demonstrated reduced Bcl‐2 expression in the ventricular zone and reduced Bcl‐2 mRNA levels . However, p53 (mRNA and protein) and activated phospho‐p53 were upregulated within the cortical zone, CA1 region, subcortical and periventricular white matter, and the amygdala .…”

“…Studies of rats with placental insufficiency at birth demonstrated reduced Bcl‐2 expression in the ventricular zone and reduced Bcl‐2 mRNA levels . However, p53 (mRNA and protein) and activated phospho‐p53 were upregulated within the cortical zone, CA1 region, subcortical and periventricular white matter, and the amygdala . Under physiological conditions, p53 should result in murine double minute 2 transcription, which functions to attenuate the apoptotic effect of p53 .…”

“…Nitric oxide synthase (NOS) plays an important role in cerebral pathology. Placental insufficiency injury results in the upregulation of calcium‐independent inducible NOS in the parietal cerebral cortex and ventricular zone at birth . Endothelial NOS is upregulated within the ventricular zone of these rats.…”

“…There was abnormal neuronal migration within the cerebral cortex There were locomotor deficits in adult male rats but not in female rats Mallard et al 25 1999 Cerebral ventricles were enlarged The cerebral cortex and hippocampal size were reduced Olivier 27 2007 There was white matter damage, increased microglia, and astrogliosis There was a reduction in preoligodendrocytes and myelination delay Uysal 29 2008 Inducible NOS and p53 within the cortex were increased Inducible NOS and endothelial NOS were increased and Bcl-2 expression decreased within the ventricular zone Lane et al 30 2001 Bcl-2 expression was decreased within the cortex Bcl-2-associated X protein and caspase-3 activity were unaffected Ke et al 31 2005…”