Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury

Jung, Peter; Ha, Euntaik; Zhang, Meijuan; Fall, Carolyn; Hwang, Mindy; Taylor, Emily; Stetkevich, Samuel; Bhanot, Aditi; Wilson, Christopher G.; Figueroa, Johnny D.; Obenaus, André; Bragg, Shannon; Tone, Beatriz; Eliamani, Saburi; Holshouser, Barbara A.; Blood, Arlin B.; Liu, Taiming

doi:10.1371/journal.pone.0268282

Cited by 7 publications

(4 citation statements)

References 60 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GSNO [ 25 , 26 ], BDNIC (binuclear DNIC), MDNIC (mononuclear DNIC) [ 27 ], and HbNO [ 28 ] were synthesized as previously described. Other chemicals were obtained from Sigma (St. Louis, MO, USA) as previously described [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites

Liu,

Zhang,

Duot

et al. 2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

We recently developed a combination of four chemiluminescence-based assays for selective detection of different nitric oxide (NO) metabolites, including nitrite, S-nitrosothiols (SNOs), heme-nitrosyl (heme-NO), and dinitrosyl iron complexes (DNICs). However, these NO species (NOx) may be under dynamic equilibria during sample handling, which affects the final determination made from the readout of assays. Using fetal and maternal sheep from low and high altitudes (300 and 3801 m, respectively) as models of different NOx levels and compositions, we tested the hypothesis that sample handling introduces artifacts in chemiluminescence assays of NOx. Here, we demonstrate the following: (1) room temperature placement is associated with an increase and decrease in NOx in plasma and whole blood samples, respectively; (2) snap freezing and thawing lead to the interconversion of different NOx in plasma; (3) snap freezing and homogenization in liquid nitrogen eliminate a significant fraction of NOx in the aorta of stressed animals; (4) A “stop solution” commonly used to preserve nitrite and SNOs leads to the interconversion of different NOx in blood, while deproteinization results in a significant increase in detectable NOx; (5) some reagents widely used in sample pretreatments, such as mercury chloride, acid sulfanilamide, N-ethylmaleimide, ferricyanide, and anticoagulant ethylenediaminetetraacetic acid, have unintended effects that destabilize SNO, DNICs, and/or heme-NO; (6) blood, including the residual blood clot left in the washed purge vessel, quenches the signal of nitrite when using ascorbic acid and acetic acid as the purge vessel reagent; and (7) new limitations to the four chemiluminescence-based assays. This study points out the need for re-evaluation of previous chemiluminescence measurements of NOx, and calls for special attention to be paid to sample handling, as it can introduce significant artifacts into NOx assays.

show abstract

Section: Methodsmentioning

confidence: 99%

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites

Liu,

Zhang,

Duot

et al. 2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

show abstract

“…The important role of nitric oxide system is due not only to neurotoxic, but also due to neuroprotective effect of NO [23], synthesized by eNOS, which acts as a vasodilator, participates in control of vasodilation and local blood flow, modulates processing of amyloid precursor protein (APP) affects functional state of microglia and cognitive functions [24]. Available data indicate a decrease in production of NO by endotheliocytes of human cerebral vessels causes an increased expression of APP and β-site of APP cleavage enzyme 1 (BACE1), which leads to an increase in secretion of β peptides (Aβ1-40 and Aβ1-42) of amyloid.…”

Section: Extrapolationmentioning

confidence: 99%

Morphofunctional changes in ventral and dorsal hippocampus in adult rats after chronic mild stress: a preclinical experimental study

Tyurenkov,

Smirnov,

Ekova

et al. 2024

Kuban. nauсh. med. vestnik

View full text Add to dashboard Cite

Background. Stressful influences, depending on their severity and duration, can cause the development of pathological conditions. Repeated episodes of stress cause functional and structural changes in the central nervous system and can cause the development of depressive conditions. Depression is one of the leading mental illnesses. One of the most stress-sensitive brain structures is the hippocampus. Objective. To study is to evaluate structural changes in the hippocampus, which is considered as a heterogeneous structure with separate dorsal and ventral regions, to evaluate the expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, serine racemase, synaptophysin in a mild stress model.Methods. A study of the effects of mild stress was carried out on 16 adult male Wistar rats (age 12 months, body weight 350–400 g). After acclimatization, the rats were divided into two equal groups (n = 8): intact (control) and stressed. When keeping animals, modeling and removing them from the experiment, we were guided by the Regulations for Carrying Out Work Using Laboratory Animals and the Declaration of Helsinki. Experimental modeling of depression in animals was induced by mild stress exposure for 7 days (30 minutes daily). Euthanasia was performed in a CO2 incubator. The brain was fixed in neutral buffered 10% formalin. Paraffin sections were made in the frontal plane, stained with hematoxylin and eosin, thionin using the Nissl method and examined at a level from –2.40 to –3.96 mm relative to bregma using an Axio Lab A1 microscope (Carl Zeiss Microscopy GmbH, Germany). Photo documentation was carried out with an AxioCam 105 color camera (Carl Zeiss Microscopy GmbH, Germany). Using the Image Analysis module of the ZEN 1.1.2.0 program (Carl Zeiss Microscopy GmbH, Germany) in the pyramidal layer of the hippocampus. Statistical analysis was performed with Microsoft Office Excel 2016 (Microsoft, USA) and Prism 6 (GraphPad Software Inc., USA). Comparisons of two conditions were made by nonparametric Mann-Whitney-U test to avoid a statistical bias of unequal data distribution. The level of significance was set at p < 0.05. The summarized data were presented as a as mean ± standard error of mean.Results. Functional research methods and assessment of pathological changes in hippocampal neurons are presented. An increase in the relative number of wrinkled hyperchromatic pyramidal neurons in the dorsal cornu ammonis field 3 in stressed rats was noted by 23.6% (p < 0.05) compared to the control. There was an increase in the relative number of inducible nitric oxide synthase-immunopositive neurons in the dorsal cornu ammonis field 3 by 40% ( p < 0.05) and the relative area of inducible nitric oxide synthase-immunoreactive material by 35% (p < 0.05) in the pyramidal layer of cornu ammonis field 3 in stressed rats. A decrease in the relative area of synaptophysin-immunopositive material in stressed rats was found in the ventral cornu ammonis field 3 compared to the control group by 16.8% (p < 0.05); decrease in the relative area of serine racemase-immunopositive material in dorsal cornu ammonis field 3 by 4.3% (p < 0.05) and ventral cornu ammonis field 3 by 7.8% (p < 0.05).Conclusion. The results of the study demonstrate that mild stress is an adequate model of depression in rats. In animals exposed to mild stress, pronounced morphological signs of damage to hippocampal neurons were revealed; motor and indicative exploratory activity decreases. Differences were found in morphofunctional changes in the dorsal and ventral parts of the hippocampus under the influence of mild stress. In cornu ammonis field 3 of the dorsal hippocampus, in contrast to the ventral section, more pronounced signs of damage to pyramidal layer neurons were observed. The increase in the relative number of inducible nitric oxide synthase-immunopositive neurons and the relative area of inducible nitric oxide synthase-immunoreactive material in the cornu ammonis field 3 pyramidal layer in stressed rats indicates an increase in nitric oxide production and the participation of nitrooxide-dependent free radical mechanisms of damage to hippocampal neurons. The decrease in the relative area of synaptophysin-immunoreactive material in stressed rats may contribute to changes in synaptic plasticity. A decrease in the relative area of serine racemase-immunoreactive material in the dorsal and ventral parts of cornu ammonis field 3 is considered to be a sign of a possible decrease in N-methyl-D-aspartate-dependent neurotransmission in the hippocampus under stress.

show abstract

“…It has been found that short-term use of NO donors before the beginning of ischemia can protect the function of endothelium in ischemic reperfusion injury [46]. It was also shown that inhalation of NO or nitrite encourages brain function during perinatal hypoxic and chemical intervention [47].…”

Section: Introductionmentioning

confidence: 99%

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury

Andrianov,

Kulchitsky,

Yafarova

et al. 2023

Molecules

View full text Add to dashboard Cite

Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level of the first lumbar vertebra. Seven days after brain injury, a reduction in NO content of 84% in injured brain regions and 66% in intact brain regions was found. The difference in NO production in injured and uninjured brain regions persisted 7 days after injury. The copper content in the brain remained unchanged one week after modeling of brain and spinal cord injury. The data obtained in the experiments help to explain the problems in the therapy of patients with combined brain injury.

show abstract

Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury

Cited by 7 publications

References 60 publications

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites

Morphofunctional changes in ventral and dorsal hippocampus in adult rats after chronic mild stress: a preclinical experimental study

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury

Contact Info

Product

Resources

About