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Open Access 01-12-2015 | Research

Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia

Authors: Ana Moraga, Jesús M Pradillo, Alicia García-Culebras, Sara Palma-Tortosa, Ivan Ballesteros, Macarena Hernández-Jiménez, María A Moro, Ignacio Lizasoain

Published in: Journal of Neuroinflammation | Issue 1/2015

Abstract

Background

Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke.

Methods

We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months).

Results

Aging increased both microglial proliferation, as shown by a higher number of BrdU⁺ cells and BrdU/Iba1⁺ cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1⁺/epidermal growth factor receptor (EGFR)⁺/nestin⁺/glial fibrillary acidic protein (GFAP)⁺ cells) and type-C cells (prominin-1⁺/EGFR⁺/nestin⁻/Mash1⁺ cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX⁺ cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN⁺/BrdU⁺ and GAD67⁺ cells) in the peri-infarct cortical area 14 days after stroke.

Conclusions

Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in the cortical peri-infarct area. Thus, our results highlight the importance of using aged animals for translation to clinical studies.

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Title: Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia
Authors: Ana Moraga
Jesús M Pradillo
Alicia García-Culebras
Sara Palma-Tortosa
Ivan Ballesteros
Macarena Hernández-Jiménez
María A Moro
Ignacio Lizasoain
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0314-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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