Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

Figure 1

Schematic overview of hypoxia-ischaemia pathology. Disruption of blood and oxygen supply results in an initial increase in blood pressure and cerebral blood flow with redistribution favoring the brain, heart, and adrenal glands, as well as reduction in ATP due to limited glucose availability. This results in intracellular accumulation of calcium and cell membrane depolarisation and initial mostly necrotic cell death. During the latent/recovery phase there is normalization of homeostasis. However, if the initial insult is prolonged or severe, this may result within hours in a secondary delayed energy failure, due to disruption of mitochondria function as a result of excitotoxicity, inflammation, and continual uptake of intracellular calcium as well as release of oxygen reactive species. It is during the secondary energy failure that most cell death occurs, with predominant apoptosis. A tertiary phase may occur within days after initial injury and continues for months. This involves late cell death, astrogliosis, remodelling, and repair. Hypothermia, the only clinical treatment available for neonatal encephalopathy, targets the latent phase.