The Neuron-Astrocyte-Microglia Triad in a Rat Model of Chronic Cerebral Hypoperfusion: Protective Effect of Dipyridamole

Frontiers in Aging Neuroscience

Anna Maria ePugliese¹  Felicita ePedata¹  Alessia eMelani¹  Daniele eLana²  Maria Grazia eGiovannini²  Sara eCipriani³ 

[1] Department NEUROFARBA;Department of Health Sciences, Section of Clinical Pharmacology and Oncology;Inserm U1141;

关键词: Apoptosis;    CA1 Region, Hippocampal;    Phagocytosis;    neuron-astrocyte-microglia triad;    2VO;   

DOI  :  10.3389/fnagi.2014.00322

来源: DOAJ

【 摘 要 】

Chronic cerebral hypoperfusion during aging may cause progressive neurodegeneration as ischemic conditions persist. Proper functioning of the interplay between neurons and glia is fundamental for the functional organization of the brain. The aim of our research was to study the pathophysiological mechanisms, and particularly the derangement of the interplay between neurons and astrocytes-microglia with the formation of triads, in a model of chronic cerebral hypoperfusion induced by the 2-vessel occlusion (2VO) in adult Wistar rats (n=15). The protective effect of dipyridamole given during the early phases after 2VO (4 mg/kg/day i.v., the first 7 days after 2VO) was verified (n=15). Sham-operated rats (n=15) were used as controls. Immunofluorescent triple staining of neurons (NeuN), astrocytes (GFAP) and microglia (IBA1) was performed 90 days after 2VO. We found significantly higher amount of ectopic neurons, neuronal debris and apoptotic neurons in CA1 Str. Radiatum and Str. Pyramidale of 2VO rats. In CA1 Str. Radiatum of 2VO rats the amount of astrocytes (cells/mm2) did not increase. In some instances several astrocytes surrounded ectopic neurons and formed a micro scar around them. Astrocyte branches could infiltrate the cell body of ectopic neurons, and, together with activated microglia cells formed the triads. In the triad, significantly more numerous in CA1 Str. Radiatum of 2VO than in sham rats, astrocytes and microglia cooperated in the phagocytosis of ectopic neurons. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Dypiridamole significantly reverted all the above described events. The protective effect of chronic administration of dipyridamole might be a consequence of its vasodilatory, antioxidant and anti-inflammatory role during the early phases after 2VO.

【 授权许可】

Unknown