Crosstalk of Astrocytes and Other Cells during Ischemic Stroke

Abstract

Stroke is a leading cause of death and long-term disability worldwide. Astrocytes structurally compose tripartite synapses, blood–brain barrier, and the neurovascular unit and perform multiple functions through cell-to-cell signaling of neurons, glial cells, and vasculature. The crosstalk of astrocytes and other cells is complicated and incompletely understood. Here we review the role of astrocytes in response to ischemic stroke, both beneficial and detrimental, from a cell–cell interaction perspective. Reactive astrocytes provide neuroprotection through antioxidation and antiexcitatory effects and metabolic support; they also contribute to neurorestoration involving neurogenesis, synaptogenesis, angiogenesis, and oligodendrogenesis by crosstalk with stem cells and cell lineage. In the meantime, reactive astrocytes also play a vital role in neuroinflammation and brain edema. Glial scar formation in the chronic phase hinders functional recovery. We further discuss astrocyte enriched microRNAs and exosomes in the regulation of ischemic stroke. In addition, the latest notion of reactive astrocyte subsets and astrocytic activity revealed by optogenetics is mentioned. This review discusses the current understanding of the intimate molecular conversation between astrocytes and other cells and outlines its potential implications after ischemic stroke. “Neurocentric” strategies may not be sufficient for neurological protection and recovery; future therapeutic strategies could target reactive astrocytes.

Gain‐of‐function of progesterone receptor membrane component 2 ameliorates ischemic brain injury

“…42 The A1-type astrocyte and M1-type microglia are viewed as causes of pro-inflammatory activities, synaptogenesis loss, white matter damage, and neuronal death, whereas the A2-type astrocytes and M2-type microglia are inflammatory-resolving and promote synaptic repair, growth, and neuronal survival. 8,9,42,43 The progesterone signaling pathway participates in the suppression of inflammation in neurological diseases, and progesterone treatment has been shown to inhibit astrocytosis, microgliosis, and oxidative stress after brain trauma in rodents. 39,44 Jiang et al 45 showed that intraperitoneal injection of progesterone suppressed TNFα levels in ischemic mouse brains, and we have consistently found that progesterone alleviates HIE-induced brain injury by regulating the activation of TNF signaling.…”

“…Resting astrocytes (A0) and microglia (M0) can be switched to their activated forms, either A1/M1 (neurotoxic) or A2/M2 (neuroprotective), in response to ischemic stroke 42 . The A1‐type astrocyte and M1‐type microglia are viewed as causes of pro‐inflammatory activities, synaptogenesis loss, white matter damage, and neuronal death, whereas the A2‐type astrocytes and M2‐type microglia are inflammatory‐resolving and promote synaptic repair, growth, and neuronal survival 8,9,42,43 . The progesterone signaling pathway participates in the suppression of inflammation in neurological diseases, and progesterone treatment has been shown to inhibit astrocytosis, microgliosis, and oxidative stress after brain trauma in rodents 39,44 .…”

Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

“…This process is thought to be critical for the repair and recovery of the brain after a stroke. Reactive astrocytes also play an important role in forming new blood vessels after stroke, which is essential for the survival and integration of new neurons in the brain [ 218 , 219 ]. Several signaling pathways have been proposed to play roles in the adult neurogenic response to ischemia-induced stroke.…”

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis

“…In addition, these cytotoxic agents activate inducible pathways NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which impair endothelial cells [ 29 ]. Following ischemic stroke, the expression of MMPs is responsible for disrupting the BBB, aggravating cerebral oedema, hemorrhagic transformation, and, ultimately, death of neuronal and glial cells [ 30 ].…”