Hypoxia–ischemia in the immature brain

Abstract

The immature brain has long been considered to be resistant to the damaging effects of hypoxia and hypoxia-ischemia (H/I). However, it is now appreciated that there are specific periods of increased vulnerability, which relate to the developmental stage at the time of the insult. Although much of our knowledge of the pathophysiology of cerebral H/I is based on extensive experimental studies in adult animal models, it is important to appreciate the major differences in the immature brain that impact on its response to, and recovery from, H/I. Normal maturation of the mammalian brain is characterized by periods of limitations in glucose transport capacity and increased use of alternative cerebral metabolic fuels such as lactate and ketone bodies, all of which are important during H/I and influence the development of energy failure. Cell death following H/I is mediated by glutamate excitotoxicity and oxidative stress, as well as other events that lead to delayed apoptotic death. The immature brain differs from the adult in its sensitivity to all of these processes. Finally, the ultimate outcome of H/I in the immature brain is determined by the impact on the ensuing cerebral maturation. A hypoxic-ischemic insult of insufficient severity to result in rapid cell death and infarction can lead to prolonged evolution of tissue damage.

Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia–Ischemia

“…The pathogenesis of brain injury is age dependent and particularly inflammatory, and caspase-dependent processes appear to be important in the immature brain (Vannucci and Hagberg, 2004). However, the role of MMP-9 in the developing brain after injury has not been evaluated.…”

Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

“…Brain damage as a consequence of perinatal cerebral hypoxia/ischemia and stroke is a major cause of acute mortality and severe chronic disabilities, and excitotoxicity is one of the crucial underlying mechanisms. Several evidences suggest that in comparison to the adult brain, the immature brain responds in a particular fashion to brain injuries, partly due to the fact that many of adult gene expression patterns, neural circuits organization, cell differentiation, and myelination have not yet been completed (Ferriero, 2004;Vannucci and Hagberg, 2004). Furthermore, as astroglial cells were the main cell type showing cleaved caspase-3 but not apoptotic cell death after neonatal excitotoxicity, the second aim was to elucidate the putative role that caspase-3 may play in proliferation and cytoskeletal reorganization in reactive astrocytes.…”

Prostaglandin D2Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

“…Neonatal hypoxic-ischemic encephalopathy (HIE) resulting from perinatal cerebral hypoxia-ischemia (HI) is one of the leading causes of acute mortality and chronic disability in infants and children (Vannucci and Hagberg, 2004;Miller et al, 2005). The incidence of systemic asphyxia is 2ϳ4/1,000 full-term infants (Vannucci and Vannucci, 2005), ϳ10% of which cases are diagnosed as HIE (American College of Obstetricians and Gynecologists and American Academy of Pediatrics, 2003).…”