Indole‐3‐carbinol ameliorated the neurodevelopmental deficits in neonatal anoxic injury in rats
- 3 November 2022
- journal article
- research article
- Published by Wiley in International Journal of Developmental Neuroscience
- Vol. 83 (1), 31-43
- https://doi.org/10.1002/jdn.10234
Abstract
Neonatal anoxia is linked to long-lasting neurodevelopmental deficits. Due to the lack of pharmacological intervention to treat neonatal anoxia, there is interest in finding new molecules for its treatment. Indole-3-carbinol (I3C) has shown neuroprotective effects in some disease conditions. However, the neuroprotective role of I3C in neonatal anoxia has not been explored. Consequently, we have investigated the effect of I3C on neonatal anoxia-induced brain injury and neurodevelopmental deficits. Rat pups after 30 h of birth were subjected to two episodes of anoxia (10 min in each) at a time interval of 24 h by flowing 100% nitrogen. I3C was administered within 30 min of the second episode of anoxia on a postnatal day (PND) 3 and continued for PND 9. Neurodevelopmental deficits, cortical mitochondrial membrane potential (MMP), opening of mitochondrial permeability transition pore (MPTP), electron transport chain (ETC) enzyme activities, oxidative stress, hypoxia-inducible factor-1 alpha (HIF-1 alpha) levels, histopathological changes, and apoptosis were measured. I3C treatment dose-dependently ameliorated the neurodevelopmental deficits and somatic growth in anoxic pups. I3C improved mitochondrial function by enhancing the MMP, mitochondrial ETC enzymes, and antioxidants. It blocked the MPTP opening and release of cytochrome C in anoxic pups. Further, I3C reduced the elevated cortical HIF-1 alpha in neonatal anoxic pups. Furthermore, I3C ameliorated histopathological abnormalities and mitochondrial-mediated apoptotic indicators Cyt C, caspase-9, and caspase-3. Our study concludes that I3C improved neuronal development in anoxic pups by enhancing mitochondrial function, reducing HIF-1 alpha, and mitigating apoptosis.Keywords
This publication has 59 references indexed in Scilit:
- Hypoxia-inducible factor 1: Regulator of mitochondrial metabolism and mediator of ischemic preconditioningBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011
- The role and regulation of hypoxia-inducible factor-1α expression in brain development and neonatal hypoxic–ischemic brain injuryBrain Research Reviews, 2009
- MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2Cell Metabolism, 2009
- The up‐regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1αJournal of Neurochemistry, 2009
- Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling methodNature Protocols, 2006
- Minocycline reduces lipopolysaccharide-induced neurological dysfunction and brain injury in the neonatal ratJournal of Neuroscience Research, 2005
- Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1α Reduces Rather Than Increases Hypoxic-Ischemic DamageJournal of Neuroscience, 2005
- Hypoxia induces the expression of the pro-apoptotic gene BNIP3Cell Death & Differentiation, 2001
- Methods of microphotometric assay of succinate dehydrogenase and cytochromec oxidase activities for use on human skeletal muscleJournal of Molecular Histology, 1989
- Some observations on the photometric estimation of mitochondrial volumeBiochimica et Biophysica Acta, 1958