Brain-immune interactions in perinatal hypoxic-ischemic brain injury

Abstract

Perinatal hypoxia-ischemia remains the primary cause of acute neonatal brain injury, leading to a high mortality rate and long-term neurological deficits, such as behavioral, social, attentional, cognitive and functional motor deficits. An ever-increasing body of evidence shows that the immune response to acute cerebral hypoxia-ischemia is a major contributor to the pathophysiology of neonatal brain injury. Hypoxia-ischemia provokes an intravascular inflammatory cascade that is further augmented by the activation of resident immune cells and the cerebral infiltration of peripheral immune cells response to cellular damages in the brain parenchyma. This prolonged and/or inappropriate neuroinflammation leads to secondary brain tissue injury. Yet, the long-term effects of immune activation, especially the adaptive immune response, on the hypoxic-ischemic brain still remain unclear. The focus of this review is to summarize recent advances in the understanding of post-hypoxic-ischemic neuroinflammation triggered by the innate and adaptive immune responses and to discuss how these mechanisms modulate the brain vulnerability to injury. A greater understanding of the reciprocal interactions between the hypoxic-ischemic brain and the immune system will open new avenues for potential immunomodulatory therapy in the treatment of neonatal brain injury.

Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic‐ischemic brain injury in the neonatal male rat

“…Increasing evidence suggests that post‐ischemic inflammation plays an important role in evolution of brain damages after ischemia (Ziemka‐Nalecz et al, 2017). Hours after onset of cerebral ischemia, a cascade of inflammatory events is initiated through activation of resident cells, among which activated microglia released inflammatory cytokines and increased neuronal death (Li et al, 2017). Our results displayed microglia activation after neonatal HI, and showed that NLRP3 expressed mainly in microglia rather than astrocyte.…”

“…Microglia is a major source of NLRP3 activation and can produce IL‐1β in response to different classical inflammasome activators, such as such as ATP and nigericin. In HIE of human infants, microglial activation and aggregation are the pathological markers(Li et al, 2017).…”

“…Hypoxia ischemia induces an inflammatory response in the brain and peripheral organs, resulting in the release of a number of pro‐ and anti‐inflammatory cytokines and chemokines, including cytokines interleukin (IL)‐1β and IL‐18 (Ziemka‐Nalecz et al, 2017; Li et al, 2017). In particular, the secretion of IL‐1β and IL‐18 requires the NOD (nucleotide‐binding oligomerization domain)‐like receptor (NLR) Pyrin domain containing 3 (NLRP3) inflammasome (Singh and Jha, 2018; Song et al, 2017).…”

“…Hypoxia ischemia induces an inflammatory response in the brain and peripheral organs, resulting in the release of a number of pro-and anti-inflammatory cytokines and chemokines, including cytokines interleukin (IL)-1β and IL-18 (Ziemka-Nalecz et al, 2017;Li et al, 2017).…”

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age

“…On the other hand, age impacts on brain functioning, once it was observed in a previous study that the same neonatal anoxia model, at PND 90, decreased the %OAT and the percentage of time spent on the closed arm was significantly higher in adult male subjected to neonatal anoxia than in control animals Which altered cellular mechanisms would be responsible for these damages? Accumulated evidence has acknowledged the following events: neuronal apoptosis, reactive gliosis, oxidative stress, excitotoxicity, inflammation and disruption of blood-brain barrier as linked to the neonatal brain damage induced by neonatal anoxia (Beilharz et al, 1995;Buwalda et al, 1995;Wei et al, 2004;Borutaite et al, 2013;Fang et al, 2017;Li et al, 2017;Li et al, 2018). Notably, sex-specificity in many of these processes occurs in normal brain development and may be a reason to male and female differentially respond to neonatal oxygen deprivation, which in turn alters their developmental program and cognitive functions, as also shown in the onset of ontogenetic reflexes and somatic development (Kumar et al, 2017).…”