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Imperial College London: Henrik Hagberg MD PhD

Henrik Hagberg MD PhD, is a professor at the Centre for the Developing Brain, the Institute of Reproductive and Developmental Biology, Imperial College in London, United Kingdom.  The research has been focused on mechanisms of perinatal brain injury. He demonstrated that brain ischemia is accompanied by massive release of excitatory amino-acids (EAAs) implicating that these compounds exert neurotoxic effects during/after ischemia in the adult and immature brain. EAAs are released also into the CSF of asphyxiated babies. He found that post-treatment with EAA receptor antagonists (NMDA and AMPA) reduced perinatal brain injury and the degree of EAA increase in CSF correlated to outcome in asphyxiated babies. There is also a delayed increase of EAAs and NO that is attenuated by hypothermia, which may be one factor of importance to explain the neuroprotective effect of lowering brain temperature. Furthermore, NMDA receptor activation enhances glucose utilization during reperfusion in the immature brain, which is most likely due to an impairment of mitochondrial function. Subsequent studies have also demonstrated a link between the NMDA receptor, mitochondrial function and triggering of the apoptotic cascade encompassing the release of pro-apoptotic molecules. He has shown that both 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 immature brain injury. Recent work show that Bax dependent mitochondrial permeabilization -rather than the mitochondrial permeability transition pore- is critical in immature brain injury. In  addition, immune cells (microglia, T-cells, neutrophils) as well as cytokines and chemokines is involved in the inflammatory response in the immature CNS (clinical and experimental studies). For example,  the IL-1 family cytokine IL-18 was shown to be important for brain recovery after hypoxia-ischemia. Several papers have been published showing that pre-exposure with systemic inflammation induced by bacterial lipopolysaccharide increases injury to subsequent hypoxic-ischemic insults (”sensitisation”) indicating  that TOLL-like receptors are important mediators of CNS vulnerability.


Dr Hagberg plans to explore the link between inflammation (microglia, mast cells) and neuronal/ oligodendroglial cell death, development and regeneration. His group plans to study the following:

Characterize the expression of death receptor ligands (TWEAK, TRAIL, Fas), death receptors (TRAIL receptors, TWEAK receptor, Fas) and decoy receptors in the immature brain and their importance in different immature brain injury and regenerative models in vivo and in vitro.

Examine the p53 regulation of Bax dependent mitochondrial permeabilisation leading to cell death and how inflammation is modulating the pathway in neurons and oligodendroglia.

Explore the role of p53 and caspases in the phenotypic expression of microglia in the immature brain.