Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression.

Abstract

AIMS:

Several lines of evidence demonstrated that endothelial nitric oxide synthase (eNOS) confers protective effects during cerebral ischemia. In this study, we explored the underlying cellular and molecular mechanisms of neuroprotection by eNOS.

METHODS:

A series of in vivo and in vitro ischemic models were employed to study the role of eNOS in maintaining neuronal survival and to identify the downstream factors.

RESULTS:

The current data showed that pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which was consistent with the findings in an oxygen-glucose deprivation model (OGD) with two neuronal cells: primary rat cortical neurons and human neuroblastoma SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was totally abolished by exogenous BDNF in both in vitro and in vivo models. On the other hand, eNOS overexpression through an adenoviral vector exerted a prominent protective effect on the neuronal cells subject to OGD, and the protective effect was totally abrogated by a neutralizing anti-BDNF antibody.

CONCLUSION:

Collectively, our results indicate that the neuroprotection of neuron-derived eNOS against the cerebral ischemia was mediated through the regulation of BDNF secretion. In conclusion, our discovery provides a novel explanation for the neuroprotective effect of eNOS under pathological ischemic conditions such as stroke.

• Authors: Shi-Ting Li, Jing Pan, Xu-Ming Hua, Hong Liu, Sa Shen, Jia-Fu Liu, Bin Li, Bang-Bao Tao, Xiao-Li Ge, Xu-Hui Wang, Juan-Hong Shi, Xiao-Qiang Wang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 2 Pg. 154-64 (Feb 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24397751 (Publication Type: Journal Article)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antibodies
• Brain-Derived Neurotrophic Factor
• Enzyme Inhibitors
• N(G)-iminoethylornithine
• Ornithine
• Nitric Oxide Synthase Type III
• Caspase 3
• Glucose

Topics

• Animals
• Antibodies (pharmacology, therapeutic use)
• Brain (drug effects, pathology)
• Brain-Derived Neurotrophic Factor (immunology, metabolism)
• Caspase 3 (metabolism)
• Cells, Cultured
• Cerebral Cortex
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation (drug effects, physiology)
• Glucose (deficiency)
• Humans
• Hypoxia (pathology, prevention & control)
• Ischemic Attack, Transient (pathology, prevention & control)
• Male
• Neurons (drug effects, physiology)
• Nitric Oxide Synthase Type III (immunology, metabolism)
• Ornithine (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley