Mild hypoxic preconditioning attenuates injury-induced NADPH-d/nNOS expression in brainstem motor neurons of adult rats

Wei, I-Hua; Huang, Chih‐Chia; Tseng, Chiu‐yu; Chang, Hui‐Ching; Tu, Hui-Chin; Tsai, Mang-Hung; Wen, Chen-Yuan; Shieh, Jeng-Yi

doi:10.1016/j.jchemneu.2007.08.008

Cited by 14 publications

(14 citation statements)

References 37 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NADPH-d used as a selective marker for nNOS as described previously [21,27,43,44]. Briefly, sections in the first two wells were incubated with NADPH-d medium (0.1 mg/ml nitroblue tetrazolium, 1 mg/ml β-NADPH, and 0.3% Triton X-100 in 0.1 M PB [pH 7.4]) for 1 h at 37°C, washed several times in 0.1 M PB to terminate the reaction.…”

Section: Methodsmentioning

confidence: 99%

(-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

Wei

Huang

et al. 2011

BMC Neurosci

Self Cite

View full text Add to dashboard Cite

BackgroundOxidative stress and large amounts of nitric oxide (NO) have been implicated in the pathophysiology of neuronal injury and neurodegenerative disease. Recent studies have shown that (-)-epigallocatechin gallate (EGCG), one of the green tea polyphenols, has potent antioxidant effects against free radical-mediated lipid peroxidation in ischemia-induced neuronal damage. The purpose of this study was to examine whether EGCG would attenuate neuronal expression of NADPH-d/nNOS in the motor neurons of the lower brainstem following peripheral nerve crush. Thus, young adult rats were treated with EGCG (10, 25, or 50 mg/kg, i.p.) 30 min prior to crushing their hypoglossal and vagus nerves for 30 seconds (left side, at the cervical level). The treatment (pre-crush doses of EGCG) was continued from day 1 to day 6, and the animals were sacrificed on days 3, 7, 14 and 28. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to assess neuronal NADPH-d/nNOS expression in the hypoglossal nucleus and dorsal motor nucleus of the vagus.ResultsIn rats treated with high dosages of EGCG (25 or 50 mg/kg), NADPH-d/nNOS reactivity and cell death of the motor neurons were significantly decreased.ConclusionsThe present evidence indicated that EGCG can reduce NADPH-d/nNOS reactivity and thus may enhance motor neuron survival time following peripheral nerve injury.

show abstract

Section: Methodsmentioning

confidence: 99%

(-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

Wei

Huang

et al. 2011

BMC Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…In human tissues, sources of ROS production include the NADPH oxidases (NOX), xanthine oxidize (XO), arachidonic acid metabolism pathways (12/15 lipoxygenase), uncoupled nitric oxide synthase (NOS), and the mitochondrial electron transport system. A large body of evidence suggests that NOX and NOS, along with an oxygen-starved mitochondrial electron transport system, comprise the major sources of ROS in the brain during hypoxia and ischemia [7,8,9,10,11,12,13,14,15,16]. …”

Section: Overview For Ros Formation Decomposition and Sourcesmentioning

confidence: 99%

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Zhao

Zhu

Fujino

et al. 2016

IJMS

154

108

View full text Add to dashboard Cite

Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS) production rapidly increases and overwhelms antioxidant defenses. A large excess of ROS will directly modify or degenerate cellular macromolecules, such as membranes, proteins, lipids, and DNA, and lead to a cascading inflammatory response, and protease secretion. These derivatives are involved in a complex interplay of multiple pathways (e.g., inflammation, apoptosis, autophagy, and necrosis) which finally lead to brain injury. In this review, we highlight the molecular mechanism for oxidative stress in HIE, summarize current research on therapeutic strategies utilized in combating oxidative stress, and try to explore novel potential clinical approaches.

show abstract

“…At the peripheral level, nNOS accumulates in the growing motor axons, eNOS is overexpressed in vasa nervorum in the distal stump and around the injury site, and iNOS is also expressed by the recruited macrophages and phagocytic Schwann cells [33]. Upregulation of nNOS, but not iNOS [14], takes place at the soma of brainstem and spinal motoneurons, which are normally lacking in this enzyme, after peripheral compression, crush, transection, and avulsion injuries in various species [14, [136][137][138][139][140][141][142][143][144][145][146][147][148]. However, eNOS induction has not been reported in injured motoneurons.…”

Section: Nos Expression Timing and No Sources In Acquired Peripheral mentioning

confidence: 99%

“…Strikingly, in the rat, the percentage of nitrergic motoneurons relative to the total pool depended on type of lesion, with the higher percentages being observed after more severe lesions. Analysis of NADPH-diaphorase histochemistry to detect NOS expression revealed that a maximum of 24-27% of the total pool of motoneurons presented nitrergic attributes after nerve crushing [14, 140,147], while in more severe injuries the proportion increased: 48-60% after transection [140][141][142] and 80-98% after avulsion [136,138,140,148]. It is remarkable that in the rat the reduction in syn-ir density in motor nuclei after nerve crushing (−9% to −33%; [13, 14, 51]) was less extensive than after transection (−60% to −68%; [55, 60]) or avulsion (−70%; [67, 69]).…”

Section: Nos Expression Timing and No Sources In Acquired Peripheral mentioning

confidence: 99%

NO Orchestrates the Loss of Synaptic Boutons from Adult “Sick” Motoneurons: Modeling a Molecular Mechanism

2010

View full text Add to dashboard Cite

Synapse elimination is the main factor responsible for the cognitive decline accompanying many of the neuropathological conditions affecting humans. Synaptic stripping of motoneurons is also a common hallmark of several motor pathologies. Therefore, knowledge of the molecular basis underlying this plastic process is of central interest for the development of new therapeutic tools. Recent advances from our group highlight the role of nitric oxide (NO) as a key molecule triggering synapse loss in two models of motor pathologies. De novo expression of the neuronal isoform of NO synthase (nNOS) in motoneurons commonly occurs in response to the physical injury of a motor nerve and in the course of amyotrophic lateral sclerosis. In both conditions, this event precedes synaptic withdrawal from motoneurons. Strikingly, nNOS-synthesized NO is "necessary" and "sufficient" to induce synaptic detachment from motoneurons. The mechanism involves a paracrine/retrograde action of NO on pre-synaptic structures, initiating a downstream signaling cascade that includes sequential activation of (1) soluble guanylyl cyclase, (2) cyclic guanosine monophosphate-dependent protein kinase, and (3) RhoA/Rho kinase (ROCK) signaling. Finally, ROCK activation promotes phosphorylation of regulatory myosin light chain, which leads to myosin activation and actomyosin contraction. This latter event presumably contributes to the contractile force to produce ending axon retraction. Several findings support that this mechanism may operate in the most prevalent neurodegenerative diseases.

show abstract

Mild hypoxic preconditioning attenuates injury-induced NADPH-d/nNOS expression in brainstem motor neurons of adult rats

Cited by 14 publications

References 37 publications

(-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

(-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

NO Orchestrates the Loss of Synaptic Boutons from Adult “Sick” Motoneurons: Modeling a Molecular Mechanism

Contact Info

Product

Resources

About