The role of the astrocyte in subarachnoid hemorrhage and its therapeutic implications

Abstract

Subarachnoid hemorrhage (SAH) is an important public health concern with high morbidity and mortality worldwide. SAH induces cell death, blood−brain barrier (BBB) damage, brain edema and oxidative stress. As the most abundant cell type in the central nervous system, astrocytes play an essential role in brain damage and recovery following SAH. This review describes astrocyte activation and polarization after SAH. Astrocytes mediate BBB disruption, glymphatic–lymphatic system dysfunction, oxidative stress, and cell death after SAH. Furthermore, astrocytes engage in abundant crosstalk with other brain cells, such as endothelial cells, neurons, pericytes, microglia and monocytes, after SAH. In addition, astrocytes also exert protective functions in SAH. Finally, we summarize evidence regarding therapeutic approaches aimed at modulating astrocyte function following SAH, which could provide some new leads for future translational therapy to alleviate damage after SAH.

Glial cell response and microthrombosis in aneurysmal subarachnoid hemorrhage patients: An autopsy study

“…Instead, the glial response has been extensively studied in experimental models of SAH. These studies showed diffuse microglial and astrocyte activation after experimental SAH ( 6 , 10 , 11 , 12 ). Following SAH, the morphology of microglia changes to an activated state, as their processes become shorter.…”

Pathophysiology, Management, and Therapeutics in Subarachnoid Hemorrhage and Delayed Cerebral Ischemia: An Overview

“…Loss of astrocytic GJs contributes to astroglial network compromise and subsequent astrocytic apoptosis [ 144 , 145 ]. However, loss of the astrocytic GJ loss diminishes the spread of Ca 2+ waves, preventing synchronized activity between neurons and vascular SMCs [ 146 ].…”

“…This cellular strategy provides another energy source (e.g., astrocyte–neuron lactate shuttle) for neurons during periods of excessive energy demand [ 150 ]. In SAH, astrocytic apoptosis is favored to precede neuronal apoptosis [ 145 ].…”

Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage

“…Astrocytes are part of the cerebral glia, tasked with the regulation of synaptic transmission, NVU function, and maintenance of blood-brain barrier integrity via their endfeet ( Figure 4 ) [ 72 , 73 , 74 ]. Under physiological conditions, they inhibit CSD initiation via K+ buffering through Na-K ATPase and glutamate uptake through GLT-1 receptors [ 53 ].…”

“…SAH patients exhibit high levels of circulating and CSF glial fibrillary protein, a marker of astrocyte activation [ 74 ]. Activated astrocytes potentiate neuroinflammation via the secretion of IL-1, IL-6, TNF-alpha, and Interferon-gamma.…”