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Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage.

Rocha-Ferreira E, Hristova M - Front Immunol (2015)

Bottom Line: They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration.Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system.Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Brain Repair Group, Department of Maternal and Fetal Medicine, Institute for Women's Health, University College London , London , UK.

ABSTRACT
Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage.

No MeSH data available.


Related in: MedlinePlus

Inflammatory response following HI injury. Neonatal asphyxia leads to activation of microglia and astrocytes, which subsequently results in increased synthesis and secretion of pro- and anti-inflammatory cytokines, reactive oxygen species, and release of matrix metalloproteinases. This is associated with BBB breakdown, as well as influx of leukocyte and lymphocyte immune cells into the injured brain.
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Figure 1: Inflammatory response following HI injury. Neonatal asphyxia leads to activation of microglia and astrocytes, which subsequently results in increased synthesis and secretion of pro- and anti-inflammatory cytokines, reactive oxygen species, and release of matrix metalloproteinases. This is associated with BBB breakdown, as well as influx of leukocyte and lymphocyte immune cells into the injured brain.

Mentions: Microglia are considered as the resident macrophages of the CNS and account for 10–20% of total glial population. Under normal physiological conditions, microglia are present in a resting state with highly ramified and motile processes. However, in the presence of environmental changes to the brain, microglia become rapidly activated, undergoing morphological changes involving retraction of processes and increase in cell body size. Depending on the extent of damage, microglial cells will further activate, become phagocytic and migrate to the site of injury (19). Microglia play an important role in HIE. Retrospective post-mortem clinical studies have shown substantial microglial activation and infiltration in the hippocampal dentate gyrus of HIE infants, which was not observed in infants who had died from trauma or sepsis (20). Microglial contribution to secondary energy failure is thought to occur via production of pro- and anti-inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) (21, 22), as well as expression of toll like receptors (TLRs) and antigen presentation (Figure 1). Microglial cells are also able to release matrix metalloproteinases, thus leading to breakdown of the BBB, allowing influx of leukocytes into the no longer immune-privileged CNS, thus exacerbating inflammation and subsequent brain damage (23). However, there are contradicting experimental mouse data on whether inhibition of microglial activation following neonatal HI is beneficial (24, 25). The microglial innate immune response is characterized by classical or M1 activation with subsequent production of associated pro-inflammatory molecules, followed by resolution and a switch to alternative or M2 phenotype leading to anti-inflammatory signaling and clearance of reactive species and wound healing (26).


Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage.

Rocha-Ferreira E, Hristova M - Front Immunol (2015)

Inflammatory response following HI injury. Neonatal asphyxia leads to activation of microglia and astrocytes, which subsequently results in increased synthesis and secretion of pro- and anti-inflammatory cytokines, reactive oxygen species, and release of matrix metalloproteinases. This is associated with BBB breakdown, as well as influx of leukocyte and lymphocyte immune cells into the injured brain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325932&req=5

Figure 1: Inflammatory response following HI injury. Neonatal asphyxia leads to activation of microglia and astrocytes, which subsequently results in increased synthesis and secretion of pro- and anti-inflammatory cytokines, reactive oxygen species, and release of matrix metalloproteinases. This is associated with BBB breakdown, as well as influx of leukocyte and lymphocyte immune cells into the injured brain.
Mentions: Microglia are considered as the resident macrophages of the CNS and account for 10–20% of total glial population. Under normal physiological conditions, microglia are present in a resting state with highly ramified and motile processes. However, in the presence of environmental changes to the brain, microglia become rapidly activated, undergoing morphological changes involving retraction of processes and increase in cell body size. Depending on the extent of damage, microglial cells will further activate, become phagocytic and migrate to the site of injury (19). Microglia play an important role in HIE. Retrospective post-mortem clinical studies have shown substantial microglial activation and infiltration in the hippocampal dentate gyrus of HIE infants, which was not observed in infants who had died from trauma or sepsis (20). Microglial contribution to secondary energy failure is thought to occur via production of pro- and anti-inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) (21, 22), as well as expression of toll like receptors (TLRs) and antigen presentation (Figure 1). Microglial cells are also able to release matrix metalloproteinases, thus leading to breakdown of the BBB, allowing influx of leukocytes into the no longer immune-privileged CNS, thus exacerbating inflammation and subsequent brain damage (23). However, there are contradicting experimental mouse data on whether inhibition of microglial activation following neonatal HI is beneficial (24, 25). The microglial innate immune response is characterized by classical or M1 activation with subsequent production of associated pro-inflammatory molecules, followed by resolution and a switch to alternative or M2 phenotype leading to anti-inflammatory signaling and clearance of reactive species and wound healing (26).

Bottom Line: They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration.Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system.Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Brain Repair Group, Department of Maternal and Fetal Medicine, Institute for Women's Health, University College London , London , UK.

ABSTRACT
Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage.

No MeSH data available.


Related in: MedlinePlus