Dataset Information

Astroglia Abnormalities in Post-stroke Mood Disorders.

ABSTRACT: Stroke is the leading cause of human death and disability. After a stroke, many patients may have some physical disability, including difficulties in moving, speaking, and seeing, but patients may also exhibit changes in mood manifested by depression, anxiety, and cognitive changes which we call post-stroke mood disorders (PSMDs). Astrocytes are the most diverse and numerous glial cell type in the central nervous system (CNS). They provide structural, nutritional, and metabolic support to neurons and regulate synaptic activity under normal conditions. Astrocytes are also critically involved in focal ischemic stroke (FIS). They undergo many changes after FIS. These changes may affect acute neuronal death and brain damage as well as brain recovery and PSMD in the chronic phase after FIS. Studies using postmortem brain specimens and animal models of FIS suggest that astrocytes/reactive astrocytes are involved in PSMD. This chapter provides an overview of recent advances in the molecular base of astrocyte in PSMD. As astrocytes exhibit high plasticity after FIS, we suggest that targeting local astrocytes may be a promising strategy for PSMD therapy.

SUBMITTER: Singer T

PROVIDER: S-EPMC9245450 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Astroglia Abnormalities in Post-stroke Mood Disorders.

Singer Tracey T Ding Sarah S Ding Shinghua S

Advances in neurobiology 20210101

Stroke is the leading cause of human death and disability. After a stroke, many patients may have some physical disability, including difficulties in moving, speaking, and seeing, but patients may also exhibit changes in mood manifested by depression, anxiety, and cognitive changes which we call post-stroke mood disorders (PSMDs). Astrocytes are the most diverse and numerous glial cell type in the central nervous system (CNS). They provide structural, nutritional, and metabolic support to neuron ...[more]

PMID: 34888833

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Project description:White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia.

Dataset Information

Astroglia Abnormalities in Post-stroke Mood Disorders.

Publications

Astroglia Abnormalities in Post-stroke Mood Disorders.

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