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Perinatal brain injury:
prevention and neuroprotective mechanisms
The research has been focused on mechanisms of brain injury and especially on perinatal brain injury.
Professor Hagberg demonstrated that reduction in oxygen to the brain (asphyxia) is accompanied by massive release of excitatory amino-acids (EAAs). We believe these compounds exert neurotoxic effects during/after ischemia. EAAs are released also in the immature brain in response to asphyxia in animals and into the fluids of the brain of asphyxiated babies. Henrik has demonstrated that treatment after injury with EAA receptor antagonists (NMDA and AMPA) reduced perinatal brain damage and that the amount of EAA in the brain fluids correlated to outcome in asphyxiated babies. There is also a delayed increase of EAAs and nitric oxide when the baby is deliberately treated with cooling. This may be an important factor explaining how the brain can be protected by reducing a baby’s temperature after asphyxia.
Brain injury sometimes results in an extension of the damage by a cascade of brain cells dying – rather like dominos over in a line being knocked over. This kind of cell death is known as apoptosis. Professor Hagberg’s more recent studies have demonstrated a link between the NMDA receptor, the function of the DNA in the mitochondria in cells, and triggering of the apoptotic cascade. Prof Hagberg has shown that various molecules are involved in this complex process. Substances called calpains (calcium activated proteases), caspases (-3, -2, -9) (proteases involved in apoptotic execution), apoptosis-inducing factor and the DNA–repair enzyme PARP interact and are important to induce brain injury. Recent work show that Bax dependent mitochondrial permeabilization (rather than the mitochondrial permeability transition pore) is critical in the brain injury of immature babies. He also demonstrated that immune cells (microglia, T-cells, neutrophils) as well as cytokines and chemokines are involved in the inflammatory response of the immature nervous system. Prof Hagberg’s group was first to demonstrate how a number of other chemical messengers may be implicated in brain injury in babies, and is devising various ways to prevent this happening.