Dying neurons conduct repair processes in the injured brain through osteopontin expression in cooperation with infiltrated blood monocytes

Abstract

The brain has an intrinsic capacity to repair injury, but the specific mechanisms are largely unknown. In this study, we found that, despite their incipient death, damaged neurons play a key repair role with the help of monocytes infiltrated from blood. Monocytes phagocytosed damaged and/or dying neurons that expressed osteopontin (OPN), with possible subsequent activation of their inflammasome pathway, resulting in pyroptosis. During this process, monocytes released CD63‐positive exosome‐like vesicles containing OPN. Importantly, following the exosome‐like vesicles, neuron and astrocyte processes elongated toward the injury core. In addition, exosomes prepared from the injured brain contained OPN, and enhanced neurite outgrowth of cultured neurons in an OPN‐dependent manner. Thus, our results introduce the concept that neurons in the injured brain that are destined to die perceive the stressful condition and begin the regeneration processes through induction of OPN, ultimately executing the repair process with the help of monocytes recruited from the circulation.

Osteopontin/secreted phosphoprotein‐1 harnesses glial‐, immune‐, and neuronal cell ligand‐receptor interactions to sense and regulate acute and chronic neuroinflammation

“…Details of the exact mechanisms remain to be further explored. Another recent study showed that dying neurons in the acute phase express OPN/SPP1 and induce similar expression in infiltrating monocytes that ultimately cooperate with other glial cells to phagocytize the damaged neurons 81 …”

“…Another recent study showed that dying neurons in the acute phase express OPN/SPP1 and induce similar expression in infiltrating monocytes that ultimately cooperate with other glial cells to phagocytize the damaged neurons. 81 Hippocampal neurons play essential roles in the consolidation of memory learning and the regulation of emotions. The neurochemical messenger dopamine regulates reward responses and is impaired in untreated HIV infection and those experiencing long-term neurologic complications.…”

Ghost messages: cell death signals spread

“…In addition, monocytes engulf dead neurons expressing osteopontin (OPN) and release exosome-like vesicles containing OPN. Following them, neurons and astrocytes carry out the regeneration and repair process [ 125 ]. ROS produced by dying hepatocytes induces release of IL-11, which triggers activation of JAK/STAT pathway in neighbor hepatocytes and compensatory proliferation [ 126 ].…”

M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina

“…Exosomes are a class of extracellular vehicles (30-150 nm diameter lipid-bilayered vesicles) containing microRNAs (miRNAs), mRNAs, and proteins 20 . Several studies have recently demonstrated that exosomes derived from damaged cells participate in many pathological situations 21 , 22 . For example, An et al found that exosomes from the injured brain could induce nearby neurons and astrocytes to migrate toward the injury core 21 .…”

“…Several studies have recently demonstrated that exosomes derived from damaged cells participate in many pathological situations 21 , 22 . For example, An et al found that exosomes from the injured brain could induce nearby neurons and astrocytes to migrate toward the injury core 21 . Awdishu et al noted that exosomes might communicate injury signals to recruit macrophage infiltration and promote inflammation after acute kidney injury 22 .…”