Combustion smoke exposure induces up-regulated expression of vascular endothelial growth factor, aquaporin 4, nitric oxide synthases and vascular permeability in the retina of adult rats

Zou, Yongchao; Lu, Jia; Poon, D.J.F.; Kaur, Charanjit; Cao, Qian; Teo, Ai Ling; Ling, Eng Ang

doi:10.1016/j.neuroscience.2009.03.007

Cited by 25 publications

(38 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have reported enhanced tissue concentration of VEGF in the hypoxic retina [13]. Here we show increased VEGF immunofluorescence in the blood vessels and astrocytes as verified by their co-localization with GFAP.…”

Section: Discussionsupporting

confidence: 78%

“…It has been suggested to be critically involved in the pathogenesis of retina edema under various injuries [13,17-19]. In the sham rats, moderate AQP4 labeling was detected in different retinal layers including the NFL, GCL, IPL, INL, OPL, and ONL (Figure 6A).…”

Section: Resultsmentioning

confidence: 98%

“…As far as can be ascertained, the effects of primary blast injury on the retina have not been reported. In view of this lack of information, we have chosen VEGF, AQP4, GS, iNOS, glutamate, and nestin as the main parameters for investigation as these factors have been reported to be closely linked to inflammation, apoptosis and edema in the brain, spinal cord, and lung after primary blast exposure [9-11,13,16,17,19,21,25,26]. …”

Section: Discussionmentioning

confidence: 99%

“…We also hypothesized that the expression of markers that are evidently linked to retinal injuries such as nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4), nestin, glutamate, and glutamine synthetase (GS) would be altered following primary blast injury. These molecules have been reported to be altered in the retina exposed to hypoxia [12] and smoke inhalation [13]. Furthermore, VEGF [14-16], AQP4 [17-19], NOS [20-22], nestin [19,23], GS [19], and glutamate [24], are known to be associated with vasodilation, tissue edema, and inflammatory reaction which have all been reported to be involved in retinal injury pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Primary blast injury-induced lesions in the retina of adult rats

Zou

Kan

et al. 2013

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundThe effect of primary blast exposure on the brain is widely reported but its effects on the eye remains unclear. Here, we aim to examine the effects of primary blast exposure on the retina.MethodsAdult male Sprague–Dawley rats were exposed to primary blast high and low injury and sacrificed at 24 h, 72 h, and 2 weeks post injury. The retina was subjected to western analysis for vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4), glutamine synthethase (GS), inducible nitric oxide synthase (NOS), endothelial NOS, neuronal NOS and nestin expression; ELISA analysis for cytokines and chemokines; and immunofluorescence for glial fibrillary acidic protein (GFAP)/VEGF, GFAP/AQP4, GFAP/nestin, GS/AQP4, lectin/iNOS, and TUNEL.ResultsThe retina showed a blast severity-dependent increase in VEGF, iNOS, eNOS, nNOS, and nestin expression with corresponding increases in inflammatory cytokines and chemokines. There was also increased AQP4 expression and retinal thickness after primary blast exposure that was severity-dependent. Finally, a significant increase in TUNEL+ and Caspase-3+ cells was observed. These changes were observed at 24 h post-injury and sustained up to 2 weeks post injury.ConclusionsPrimary blast resulted in severity-dependent pathological changes in the retina, manifested by the increased expression of a variety of proteins involved in inflammation, edema, and apoptosis. These changes were observed immediately after blast exposure and sustained up to 2 weeks suggesting acute and chronic injury mechanisms. These changes were most obvious in the astrocytes and Müller cells and suggest important roles for these cells in retina pathophysiology after blast.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Primary blast injury-induced lesions in the retina of adult rats

Zou

Kan

et al. 2013

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Accordingly, brain manifestations of acute exposure to combustion smoke span a broad range of adversely affected targets (Lee et al, 2005; Lee et al, 2009; Zou et al, 2009; Lee et al, 2010; Lee et al, 2011; Zou et al, 2013) and we sought to identify those targets, which are protected by neuroglobin in this setting. To this end, we first produced a transgenic mouse with neuron-specific overexpression of Ngb and demonstrated that Ngb protects primary neurons by raising the threshold of nitric oxide mediated neuronal injury (Singh et al, 2013) and that in vivo, elevated Ngb attenuates the formation of smoke-induced oxidative DNA damage in the mouse brain (Lee et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

Gorgun

Zhuo

Singh

et al. 2014

Inhalation Toxicology

View full text Add to dashboard Cite

Context Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (neuron specific globin protein) attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by neuroglobin in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective To determine to what extent elevated neuroglobin ameliorates post smoke-inhalation brain bioenergetics and homeostasis in neuroglobin overexpressing transgenic mouse. Methods Smoke inhalation induced changes in bioenergetics were measured in the wild type and neuroglobin transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results Cortical mitochondria from neuroglobin transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in neuroglobin transgene compared to wild type brain after smoke. Conclusion Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the neuroglobin overexpressing mouse, suggesting that neuroglobin mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury.

show abstract

Development of the fovea

Bringmann

Wiedemann

2022

The Fovea

View full text Add to dashboard Cite

Combustion smoke exposure induces up-regulated expression of vascular endothelial growth factor, aquaporin 4, nitric oxide synthases and vascular permeability in the retina of adult rats

Cited by 25 publications

References 28 publications

Primary blast injury-induced lesions in the retina of adult rats

Primary blast injury-induced lesions in the retina of adult rats

Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

Development of the fovea

Contact Info

Product

Resources

About