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J Mol Histol. 2016 Jun;47(3):259-71. doi: 10.1007/s10735-016-9670-7. Epub 2016 Mar 16.

Adenosine kinase facilitated astrogliosis-induced cortical neuronal death in traumatic brain injury.

Author information

1
Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China.
2
Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China. renchuancheng@outlook.com.

Abstract

Adenosine kinase (ADK) plays a pivotal role in regulating brain function by regulating adenosine level, and ADK inhibition protects against neuronal damage in cerebral ischemia and epilepsy; however, the effects of ADK in traumatic brain injury (TBI) have not been investigated. For exploring its effects, we generated a blade-induced rat focal brain injury model. Western blot analysis, immunohistochemistry and immunofluorescent staining suggested that ADK was up-regulated after TBI, and it was temporally and spatially associated with astrogliosis. Terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling showed that neuronal apoptosis was paralleled with TBI-induced ADK up-regulation and astrogliosis. For further investigating the role of ADK in astrogliosis-induced neuronal death, primary cultured astrocytes and neurons were utilized, lipopolysaccharide (LPS) was employed to mediate astrogliosis, and condition medium (CM) of reactive astrocytes was used to treat neurons. The results showed that astrocytes increased iNOS expression and secreted pro-inflammatory cytokines after LPS treatment, and CM of reactive astrocytes resulted neuronal death. Additionally, ADK knock-down didn't ameliorate LPS-induced astrocyte proliferation, but it protected against neuronal death by reducing iNOS expression, tumor necrosis factor α and interleukin 1β secretion of reactive astrocytes. Taken together, ADK was associated with astrogliosis after TBI, its inhibition in reactive astrocytes ameliorated astrogliosis-induced neuronal death. Our findings extended the current knowledge on the role of ADK in astrogliosis, and also provided new evidence for the TBI treatment.

KEYWORDS:

Adenosine kinase; Astrogliosis; Lipopolysaccharide; Neuron; Traumatic brain injury

PMID:
26983602
DOI:
10.1007/s10735-016-9670-7
[Indexed for MEDLINE]

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