Immunomodulatory Mechanism and Potential Therapies for Perinatal Hypoxic-Ischemic Brain Damage

Abstract

Hypoxia-ischemia (HI) is one of the most common causes of death and disability in neonates. Currently, the only available licensed treatment for perinatal HI is hypothermia. However, it alone is not sufficient to prevent the brain injuries and/or neurological dysfunction related to HI. Perinatal HI can activate the immune system and trigger the peripheral and central responses which involve the immune cell activation, increase in production of immune mediators and release of reactive oxygen species. There is mounting evidence indicating that regulation of immune response can effectively rescue the outcomes of brain injury in experimental perinatal HI models such as Rice-Vannucci model of newborn hypoxic-ischemic brain damage (HIBD), local transient cerebral ischemia and reperfusion model, perinatal asphyxia model, and intrauterine hypoxia model. This review summarizes the many studies about immunomodulatory mechanisms and therapies for HI. It highlights the important actions of some widely documented therapeutic agents for effective intervening of HI related brain damage, namely, HIBD, such as EPO, FTY720, Minocycline, Gastrodin, Breviscapine, Milkvetch etc. In this connection, it has been reported that the ameboid microglial cells featured prominently in the perinatal brain represent the key immune cells involved in HIBD. To this end, drugs, chemical agents and herbal compounds which have the properties to suppress microglia activation have recently been extensively explored and identified as potential therapeutic agents or strategies for amelioration of neonatal HIBD.

Improvement influenza vaccine immune responses with traditional Chinese medicine and its active ingredients

“…Breviscapine had a stronger effect in promoting bone marrow cell maturation and tended to regulate innate immunity. This is different from the conventional understanding of the use of breviscapine in cardiovascular disease (Min et al, 2020), but it has an antiinflammatory effect, and inflammation is closely related to immunity, so the relationship between breviscapine and immunity can be further studied from the perspective of inflammation. The ability of andrographolide to regulate the organ index and spleen lymphocyte subtypes was more prominent and tended to regulate adaptive immunity.…”

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

“…When they become activated by inflammation, microglial cells switch to a pro-inflammatory state and increase in number. They attract peripheral immune cells to the central nervous system by producing and releasing numerous inflammatory mediators such as IL-1B, IL-6, and tumor necrosis factor α [ 28 , 29 ]. IL-1B, a leading pro-inflammatory cytokine, represents a crucial step of the neuroinflammatory cascade.…”

“…In the presence of an intense neuroinflammatory process, the S-100B protein, a calcium-binding peptide [ 32 ], is a reliable indicator to measure the extent of brain damage through glial activation and/or death when is released into the circulation from its major sources, astroglial and Schwann cells [ 33 ]. These glial cells closely interact with microglia and the inflammatory factors release a myelin formation in the brain, thus modulating the response to various brain injuries [ 28 ]. In small amounts, due to paracrine and autocrine effects on neurons and glia, S-100B plays an important role in neurodevelopment and recovery after injury [ 34 ].…”

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

“…In addition, the infiltration of peripheral immune cells can affect the tissue damage, protection, repair, and regeneration of HIBD [ 15 ]. More importantly, monitoring brain immunity and inflammation can guide clinical decision-making [ 16 ]. Ferroptosis is crucial in regulating the function of immune cells, mainly including the number and function of immune cells affected by ferroptosis of immune cells and the inflammatory immune response initiated by ferroptosis of non-immune cells [ 17 ].…”