Overexpression of Adiponectin Improves Neurobehavioral Outcomes After Focal Cerebral Ischemia in Aged Mice

Miao, Jie; Shen, Lin; Tang, Yao Hui; Wang, Yong Ting; Tao, Meixin; Jin, Kunlin; Zhao, Yong; Yang, Guo Yuan

doi:10.1111/cns.12198

Cited by 38 publications

(35 citation statements)

References 57 publications

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“…Previous studies have demonstrated that adiponectin increases insulin sensitivity, displays anti-atherogenic activity, and regulates the levels of glucose and fatty acids [10,11]. Recently, the association of adiponectin with neurological diseases, including both cerebrovascular diseases and NDDs, has attracted attention [48,53,55,61,64,67,72]. However, the exact role of adiponectin in the CNS is unclear.…”

Section: Discussion and Future Prospectsmentioning

confidence: 99%

“…Numerous studies have examined the association between adiponectin and neurological diseases [48,53,55,61,64,67,72]. Most of the available data are clinical [44,45] and do not fully provide insight regarding causality.…”

Section: Discussion and Future Prospectsmentioning

confidence: 99%

“…Interestingly, adiponectin overexpression reduces ischemic brain injury and improves neurobehavioral functional recovery in aged mice relative to young mice, suggesting that adiponectin may be of benefit to aged animals after ischemic stroke [53]. Despite moderate associations between high-molecular weight (HMW) adiponectin and cardiovascular disease and the observation that an altered plasma adiponectin level is associated with cerebral ischemia incidence, there is no evidence of an association between the HMW adiponectin levels and the ischemic stroke incidence in postmenopausal women [54].…”

Section: Cerebral Ischemic Injurymentioning

confidence: 99%

See 2 more Smart Citations

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Yang

Jiang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Section: Discussion and Future Prospectsmentioning

confidence: 99%

Section: Discussion and Future Prospectsmentioning

confidence: 99%

Section: Cerebral Ischemic Injurymentioning

confidence: 99%

See 1 more Smart Citation

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Yang

Jiang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Section: Introductionmentioning

confidence: 99%

“…In experimental neurosciences, the delivery of vectors such as plasmids or adenoviruses has become an important tool for studying long-term actions of proteins in the brain 3,4 . Single injections of vectors present the advantage of a system which by itself will maintain highly stable levels of the therapeutic agent in the brain 4 . However, for long term experiments with purified drugs systemic administration by intraperitoneal injection induces stress in mice or rats, and is not the best choice when a targeted brain response is needed, requiring also large doses of drug 5 .…”

Section: Introductionmentioning

confidence: 99%

Implantation of Miniosmotic Pumps and Delivery of Tract Tracers to Study Brain Reorganization in Pathophysiological Conditions

Sánchez-Mendoza

Carballo

Longart

et al. 2016

JoVE

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Pharmacological treatment in animal models of cerebral disease imposes the problem of repeated injection protocols that may induce stress in animals and result in impermanent tissue levels of the drug. Additionally, drug delivery to the brain is delicate due to the blood brain barrier (BBB), thus significantly reducing intracerebral concentrations of selective drugs after systemic administration. Therefore, a system that allows both constant drug delivery without peak levels and circumvention of the BBB is in order to achieve sufficiently high intracerebral concentrations of drugs that are impermeable to the BBB. In this context, miniosmotic pumps represent an ideal system for constant drug delivery at a fixed known rate that eludes the problem of daily injection stress in animals and that may also be used for direct brain delivery of drugs. Here, we describe a method for miniosmotic pump implantation and post operatory care that should be given to animals in order to successfully apply this technique. We embed the aforementioned experimental paradigm in standard procedures that are used for studying neuroplasticity within the brain of C57BL6 mice. Thus, we exposed animals to 30 min brain infarct and implanted with miniosmotic pumps connected to the skull via a cannula in order to deliver a pro-plasticity drug. Behavioral testing was done during 30 days of treatment. After removal the animals received injections of anterograde tract tracers to analyze neuronal plasticity in the chronic phase of recovery. Results indicated that neuroprotection by the delivered drug was accompanied with increase in motor fibers crossing the midline of the brain at target structures. The results affirm the value of these techniques for drug administration and brain plasticity studies in modern neuroscience.

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Effect of HMGB1 on the Paracrine Action of EPC Promotes Post-Ischemic Neovascularization in Mice

et al. 2014

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Transplantation of endothelial progenitor cells (EPCs) leads to better outcomes in experimental stroke, but the mechanism remains unclear. It was reported that astrocytic-high mobility group box1 (HMGB1) promoted endogenous EPC-mediated neurovascular remodeling during stroke recovery. It is unclear whether HMGB1 involves in exogenous EPC-mediated stroke recovery. In this study, we aim to explore whether microglial HMGB1 contributes to human peripheral blood-derived (hPB)-EPCs-mediated neurovascular remodeling by modulating the paracrine function of exogenous hPB-EPCs. Coculturing hPB-EPCs with lipopolysaccharides stimulated BV2 cells upregulated Interleukin-8 expression in hPB-EPCs; this was blocked by treating BV2 cells with HMGB1 inhibitor Glycyrrhizin. Conditioned medium (CM) of hPB-EPCs cocultured with BV2 cells promoted the viability and tube formation of human umbilical cord vein cells. Inhibiting either HMGB1 or IL-8 could block the effect of hPB-EPCs CM. In vivo study showed hPB-EPCs transplantation improved neurobehavioral outcomes, reduced brain atrophy volume, and enhanced neovascularization in transient middle cerebral artery occlusion (tMCAO) mice. Intraperitoneally administration of HMGB1 inhibitor glycyrrhizin blocked the beneficial effect of hPB-EPC transplantation. We did not observe the integration of green fluorescent protein-labeled hPB-EPCs with microvessels in peri-infarct areas at day-14 after tMCAO. In summary, the result suggested that HMGB1 upregulation in postischemic brain could promote exogenous hPB-EPC-mediated stroke recovery by modulating paracrine function of hPB-EPCs.

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Overexpression of Adiponectin Improves Neurobehavioral Outcomes After Focal Cerebral Ischemia in Aged Mice

Abstract: Our results demonstrate that APN overexpression reduces ischemic brain injury and improves neurobehavioral function recovery in aged mice than in young mice, suggesting APN is more beneficial in aged animals after ischemic stroke.

Cited by 38 publications

References 57 publications

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Implantation of Miniosmotic Pumps and Delivery of Tract Tracers to Study Brain Reorganization in Pathophysiological Conditions

Effect of HMGB1 on the Paracrine Action of EPC Promotes Post-Ischemic Neovascularization in Mice

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