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Prof Donald Peebles
240
Medical School Building
74 Huntley Street
London
WC1E 6AU
Appointment
  • Chair of Obstetrics
  • Maternal & Fetal Medicine
  • Inst for Women's Health
  • Faculty of Population Health Sciences
Research Summary
Research Overview This multidisciplinary group consists of clinical obstetricians and neonatologists (Peebles, Kendall) and basic neuroscientists (Raivich, Hristova) who share the long term aim of devising therapeutic interventions to reduce the incidence of long term neuro-disability in infants born prematurely or following peri-partum hypoxia-ischaemia. The group works in close collaboration with the neonatal brain research group and jointly they have shared interests and complementary skills. The main areas of research activity include: (1) Molecular signals involved in mediating axonal damage in perinatal subcortical white matter. Immature subcortical white matter in the external and internal capsule is particularly susceptible to infection and hypoxic/ischemic insults and is associated with a high rate of cerebral palsy and poor neurodevelopmental outcome in very premature babies, born before 32 weeks of gestation. Recent studies from our laboratory show rapid, white matter-associated induction of transcription factors and stress-activated protein kinases (SAPK) such as ERK1/2, which can be blocked by specific pharmacological agents and/or in transgenic animals. This aspect of the research strategy is proving highly successful with recent grant funding success (Wellbeing - Raivich/Peebles; SPARKS â€" Raivich/Hristova/Peebles). (2) In collaboration with Prof Adrian Thrasher, Dept Ped Immunology at Institute of Child Health, we are currently constructing viral vectors that could be used to block this post-traumatic molecular activation, to prevent further brain damage and enhance neural repair. Similar research strategies to improve repair and functional recovery in the injured adult spinal cord have received strong support from International Spinal Research Trust, Glaxo and BBSRC (Raivich). (3) Analysis of pH changes in hypoxic and posthypoxic brain. Clinical studies demonstrate progressive acidosis during hypoxic ischemic insult and a rebound alkalosis in the reperfusion phase in both adult stroke and neonatal HI, there is also growing evidence that alkalosis correlates with outcome. Studies in our group using high resolution pH ex vivo imaging with Neutral Red revealed that this alkalotic shift is a global phenomenon, and that events in the remainder of the brain may have a direct influence on the fate of the injured region and hence therapeutic interventions aimed altering / preventing rebound alkalosis in the uninjured regions of the brain may confer neuroprotection. Moreover, blood brain permeable drugs blocking rebound alkalosis appear effective as neuroprotectants. We are currently exploring the role of upstream signaling cascade, particularly that of SAPK in the regulation of Na+/H+-transporters and rebound alkalosis (Action Medical Research - Raivich/Kendall/Peebles). (4) Investigating the synergistic interaction between inflammation and hypoxia-ischaemia in causing neural cell death in the developing brain. This fruitful series of experiments supports the concept of cerebral palsy resulting from multiple insults occurring around the time of delivery. Recent results suggest a key role for components of the neuro-inflammatory cascade and the Tumour Necrosis Factor (TNF) cluster of cytokines in particular (funding Action Medical Research â€" Raivich/Kendall/Peebles). (5) Effects of antenatal exposure to infection and growth restriction on cerebral metabolism and cell death in the chick embryo using MRI, spectroscopy, and immunostaining Recent studies have demonstrated the detrimental effects of even minor increases in ambient temperature on neuronal survival following transisent hypoxia-ischaemia and have also explored the effects of endotoxin on cerebral metabolism, using MRS/MRI (funding; the Wellcome Trust). (6) Studies of the expression of pro- and anti-inflammatory cytokines in mothers and infants following very preterm labour (monocyte HLA-DR expressi
Academic Background
1994 MD Doctor of Medicine University of London
1986 MBBS Bachelor of Medicine/Bachelor of Surgery University of London
1983 BA Bachelor of Arts University of Cambridge
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