laboratory-administration-transcutaneous-auricular-vagus-nerve

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus ...

Medical University of South Carolina

To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial.

Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.

Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. 

Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia.

Hypothermia treatment neuroprotects approximately 50% of neonates who present with moderate to severe hypoxic ischemic encephalopathy (HIE). N-acetylcysteine (NAC), a potent antioxidant, is neuroprotective in combination with hypothermia in neonatal hypoxia-ischemia (HI) female rats, but less protective in males. Vitamin D is a neurosteroid, which may provide immunomodulation and improve outcomes for both sexes. We investigated the efficacy of this combination of drugs with hypothermia after severe HI, as well as potential mechanisms of vitamin D effects in the transition to chronic inflammation. DOL 7 rats were randomized to sham, or HI and hypothermia treated with either saline (HYPO), NAC (50 mg/kg/d, HNAC), or HNAC plus 1,25-dihydroxy-vitamin D (0.1 μg/kg/d, HNAC + VitD) daily for 2 weeks. A second set of animals were randomized and treated for 11 days to investigate vitamin D metabolism and inflammatory mediators. Rats treated with HNAC + VitD performed significantly better on tests of strength and use of affected limb, adaptive sensorimotor skills, motor sequence learning, and working memory than either HYPO or HNAC, particularly benefiting male rats. Significantly fewer rats in the HNAC + VitD group had severe hemispheric volume loss. HI injury decreased serum vitamin D at 11 days and induced the enzyme that deactivates vitamin D in the hippocampus, particularly in males. Persistent vitamin D dysregulation was seen in both hippocampi in males, which was not reversed by hypothermia. Vitamin D in combination with hypothermia and NAC supports functional recovery in both sexes of neonatal rats significantly better than hypothermia alone or hypothermia and NAC in this severe HI model.

Article	Year
Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis. The Journal of pediatrics\| PubMed ID: 26545726	2016
Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. Neuroscience research\| PubMed ID: 26851769	2016
Vitamin D improves functional outcomes in neonatal hypoxic ischemic male rats treated with N-acetylcysteine and hypothermia. Neuropharmacology\| PubMed ID: 28599922	2017

Dorothea D. Jenkins

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