Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke

Abstract

Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration either directly or by modulating the properties of brain-resident immune cells. Immune-related signalings and metabolites from the gut microbiota can also directly alter the phenotypes of resident immune cells to promote neuronal regeneration. In this review, we discuss several potential mechanisms through which peripheral and brain-resident immune components can cooperate to promote first the resolution of neuroinflammation and subsequently to improved neural regeneration and a better functional recovery. We propose that new insights into discovery of regulators targeting pro-regenerative process in this complex neuro-immune network may lead to novel strategies for neuronal regeneration.

The Microbiota-Gut-Brain Axis in Health and Disease and Its Implications for Translational Research

“…Gut microbiota can promote neuronal regeneration via immune-related signaling and metabolites that can directly alter the phenotypes of resident immune cells. Circulating immune cells that have been shaped by immune components including the gut microbiota and their metabolites can infiltrate the brain and influence neuronal regeneration directly or through modulation of the properties of brain-resident immune cells in an ischemic brain (Liu et al, 2020). Thereby, gut microbiota and associated metabolites could be a component of a repair system after stroke that can strengthen repair-promoting immune responses or weaken neurotoxic immune responses to promote neuroplasticity (Feng et al, 2017;Jian et al, 2019).…”

Gut Microbiota Extracellular Vesicles as Signaling Molecules Mediating Host-Microbiota Communications

“…Although many studies support the microbiota–gut–brain axis’s existence, there is a limited understating of how signals are transferred from the gut to the brain. However, there is evidence that the gut can modulate the CNS through some pathways ( Table 3 , Figure 4 ): (i) the gut microbiota can captivate the neural signaling between the brain and the gut through the interaction between the vagal nerve and the enteric nervous system (ENS) [ 118 , 119 , 120 , 121 , 122 ]; (ii) the endocrine response of the host can communicate the gut microbes’ signal to the brain through circulation [ 123 , 124 ]; (iii) the gut microbe can modulate the central and peripheral immune cells, resulting in changes in stress and behavioral responses [ 125 , 126 , 127 , 128 , 129 , 130 ]; and (iv) gut microbes release metabolites, such as neurotransmitters, that can travel through the circulation of the CNS [ 131 , 132 ].…”

Treating Cerebral Ischemia: Novel Therapeutic Strategies from Experimental Stroke Research

“…After brain injury, the gut microbiome is altered and in turn modulates stroke outcome via modulation of postischemic inflammatory responses (92). Currently, the first clinical trials are conducted to further investigate how dysbiosis of the gut microbiome may influence immune response and outcome after stroke (93).…”