The impact of paracrine signaling in brain microvascular endothelial cells on the survival of neurons

被引：34

作者：

Li, Weihong ^{[1
]}

Li, Pengtao ^{[1
]}

Hua, Qian ^{[1
]}

Hou, Jincai ^{[1
]}

Wang, Jun ^{[1
]}

Du, Huan ^{[1
]}

Tang, Huiling ^{[1
]}

Xu, Ya ^{[1
]}

机构：

[1] Beijing Univ Chinese Med, Sch Preclin Med, Beijing 100029, Peoples R China

来源：

BRAIN RESEARCH | 2009年 / 1287卷

基金：

中国国家自然科学基金;

关键词：

Brain microvascular endothelial cell; Paracrine; Neuron; Calcium overload; Mitochondrium;

D O I：

10.1016/j.brainres.2009.06.057

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neurons depend for survival on local neurotrophic factors which act in an autocrine/paracrine manner. However, the effect of paracrine signaling of brain microvascular endothelial cells (BMECs) under pathological conditions on neuron survival is not fully understood. in this study we cultured rat BMECs and cortical neurons. BMECs were cultured in oxygen-glucose-deprived (OGD) conditions to mimic cerebral ischemia in vitro. The conditioned media of normal BMECs or OGD-injured BMECs were used to culture normal or injured neurons. Neuron activity, free Ca2+ concentration, NMDA receptor status, mitochondrial membrane potential and cytochrome C release level were determined. The results showed: mitochondrial activity of injured neurons was significantly increased and lactate dehydrogenase (LDH) leakage was decreased (P<0.05) by grown in conditioned medium of normal BMECs. Inversely, mitochondrial activity of normal or injured neurons was decreased and LDH leakage was significantly increased (P<0.05) by grown in conditioned medium of injured BMECs. The changes in free Ca2+ concentration, NMDA receptor status, mitochondrial membrane potential and cytochrome C release level were consistent with the changes in neuronal activity. These findings suggest that the conditioned medium of normal BMECs has a neuroprotective effect. However, this protective effect was lost after BMECs injury; in fact, the conditioned medium became neurotoxic. Therefore, it appears that early recovery of BMECs might be helpful for neuron survival. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：28 / 38

页数：11

共 24 条

[1] Astrocyte-endothelial interactions at the blood-brain barrier [J].

Abbott, NJ ;

Rönnbäck, L ;

Hansson, E .

NATURE REVIEWS NEUROSCIENCE, 2006, 7 (01) :41-53

[2]

ADRAIN C, 2001, TRENDS BIOCHEM SCI, V6, P290

[3]

Baiguera S, 2004, INT J MOL MED, V14, P849

[4] Hypoxia-tolerant neonatal CA1 neurons. relationship of survival to evoked glutamate release and glutamate receptor-mediated calcium changes in hippocampal slices [J].

Bickler, PE ;

Hansen, BM .

DEVELOPMENTAL BRAIN RESEARCH, 1998, 106 (1-2) :57-69

[5] The Apaf-1 apoptosome: a large caspase-activating complex [J].

Cain, K ;

Bratton, SB ;

Cohen, GM .

BIOCHIMIE, 2002, 84 (2-3) :203-214

[6] Blood vessels and nerves: Common signals, pathways and diseases [J].

Carmeliet, P .

NATURE REVIEWS GENETICS, 2003, 4 (09) :710-720

[7] Serotonin in the regulation of brain microcirculation [J].

Cohen, Z ;

Bonvento, G ;

Lacombe, P ;

Hamel, E .

PROGRESS IN NEUROBIOLOGY, 1996, 50 (04) :335-+

[8] The role of neuronal signaling in controlling cerebral blood flow [J].

Drake, Carrie T. ;

Iadecola, Costantino .

BRAIN AND LANGUAGE, 2007, 102 (02) :141-152

[9] Glial neuronal signaling in the central nervous system [J].

Hansson, E ;

Rönnbäck, L .

FASEB JOURNAL, 2003, 17 (03) :341-348

[10] Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma [J].

Leventhal, C ;

Rafii, S ;

Rafii, D ;

Shahar, A ;

Goldman, SA .

MOLECULAR AND CELLULAR NEUROSCIENCE, 1999, 13 (06) :450-464

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