The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease

Spuch, Carlos; Antequera, Desireé; Portero, Aitziber; Orive, Gorka; Hernández, Rosa María; Molina, José Antonio; Bermejo‐Pareja, Félix; Pedraz, José Luís; Carro, Eva

doi:10.1016/j.biomaterials.2010.03.042

Cited by 110 publications

(77 citation statements)

References 47 publications

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“…These effects may be visualized as increased T 2 and ADC values and decreased MT values in the corresponding images. We detect increased T 2 intensity values in the hippocampus and cortex of the A␤PP/PS1 mice compatible with the signs of neuroinflammation and neurodegeneration previously described in this model of AD [23].…”

Section: Discussionsupporting

confidence: 53%

“…The AD model used in the present study was previously characterized by the amyloid burden, behavioral deficit, and neuronal degeneration and synaptic loss [20,23,24]. Together with the MRI/MRS methods described here, it now represents a well-characterized model for preclinical imaging and pathological studies of AD.…”

Section: Discussionmentioning

confidence: 99%

“…A␤ is deposited progressively in the brain of these mice beginning at eight weeks of age [21], associated with extensive dystrophy of neurites. In addition, these mice, carrying mutations in the two AD proteins, depict signs of apoptotic cell death in the hippocampus and cerebral cortex of six-nine month-old animals [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Esteras

Alquézar

Antequera

et al. 2012

JAD

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Abstract. Murine models of Alzheimer's disease (AD) provide means to detect and follow biomarker changes similar to those observed in humans. Non-invasive biomarkers, such as those provided by magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are highly desirable, however, systematic studies of in vivo MRI/MRS methods to characterize the cerebral morphology and metabolic pattern of these mice remain scarce. We investigated sixteen consecutive slices from the brain of wild-type and A␤PP/PS1 mice, obtaining a collection of T 2 -weighted, diffusion weighted and magnetization transfer weighted images as well as 1 H PRESS spectra from the cortical and subcortical areas. Compared to controls, A␤PP/PS1 mice show significant regional hyperintensities in T 2 -weighted images of the cerebral cortex, significant ventricular enlargement, and decreased hippocampal area and fractional magnetization transfer. MRS demonstrated an increase in the ratio of choline (Cho) to creatine (Cr) in the cortical and subcortical areas of the transgenic animals. A logistic regression classifier was implemented considering all parameters investigated, and revealed the most characteristic changes and allowed for the correct classification of control and A␤PP/PS1 mice. In summary, the present results provide a useful frame to evaluate optimal MRI/MRS biomarkers for the characterization of AD models, potentially applicable in drug discovery processes, because of their non-invasive and repeatable nature in longitudinal studies.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Esteras

Alquézar

Antequera

et al. 2012

JAD

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“…VEGF has also been identified as an important vasculoprotective factor promoting endothelial cell (EC) survival [16]. Evenly important, VEGF is also critical as survival factor of retinal neurons and a neuroprotectant in various conditions such as ischemic injury [17], nerve regeneration [18], Parkinson's disease [19], and Alzheimer's disease [20]. Thus, early upregulation of VEGF in the diabetic retina may represent the increased need for cellular survival support.…”

Section: Introductionmentioning

confidence: 99%

Long-term Treatment with Suberythropoietic Epo is Vaso- and Neuroprotective in Experimental Diabetic Retinopathy

Wang

Gorbey

Pfister

et al. 2011

Cell Physiol Biochem

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Background/Aims: Diabetic retinopathy is characterized by pericyte loss and vasoregression both in the clinic and in animal models. A mild neurodegeneration with loss of ganglion cells is also described in the diabetic retina. Like VEGF-A, Epo is angioprotective and, in high doses, neuroprotective, however, without affecting vessel permeability. This study was to investigate the effect of a long-term suberythropoietic dose of Epo on vascular damage and neurodegeneration in a rat model of diabetic retinopathy. Methods: We administered Epo 3x256 IU/kg body weight/week to streptozotocin-diabetic Wistar rats for up to 6 months. Leukostasis was analyzed by quantitation of CD45 positive cells adherent to the retinal microvasculature. VEGF-A levels were assessed by Elisa at 3 months of treatment. Vasoregression was quantified in retinal digest preparations after 6 months of Epo treatment.Neurodegeneration was analyzed from PAS stained retinal paraffin preparations. Results: Leukostasis was unaffected by treatment with Epo which significantly inhibited the loss of pericyte and the formation of acellular capillaries. Neurodegeneration in the diabetic retina was significantly reduced by Epo treatment. Increased VEGF-A levels in the diabetic retina were normalized by Epo treatment. Conclusions: Suberythropoietic Epo is effective to protect microvascular and neuronal damage in the experimental diabetic retina.

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“…Cell microencapsulation presents the potential to deliver the therapeutic product of interest directly to the Central Nervous System (CNS). This has been achieved by different groups for brain tumors (Kuijlen et al 2007) and neurodegenerative diseases (Spuch et al 2010). A phase I clinical trial was conducted in Huntington's patients without signs of toxicity (Bloch et al 2004).…”

Section: Cell Microencapsulationmentioning

confidence: 99%

Non Viral Gene Transfer Approaches for Lysosomal Storage Disorders

Matte¹,

Baldo²,

Giugliani³

2011

Non-Viral Gene Therapy

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The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease

Cited by 110 publications

References 47 publications

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Long-term Treatment with Suberythropoietic Epo is Vaso- and Neuroprotective in Experimental Diabetic Retinopathy

Non Viral Gene Transfer Approaches for Lysosomal Storage Disorders

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