Dr. Ravindranath: Brain-related diseases affect more people than any other major disease group, including cardiovascular diseases or cancer. Treatment costs, rehabilitation and related consequences of brain-related diseases are high. The need for better understanding of brain functions, the development of innovative new drugs and determining their efficacy have provided new initiative for neuroscience research and prompted the declaration of the 1990's as the 'Decade of the Brain'. One of the major challenges facing neuroscientists today is the identification of molecular mechanisms involved in the pathogenesis and progression of neuro-generative disorders such as Parkinson's disease, Alzheimer's disease and motor neuron diseases. Exposures to environmental toxicants have been implicated in the pathogenesis of these disorders. Oxy-free radical mediated damage has also been related to the pathogenesis of motor neuron diseases and in the neuronal injury during reperfusion following cerebral ischemia (stroke). Dr. Ravindranath's research has essentially focussed on these areas of work, with particular reference to the understanding of the xenobiotic metabolising capability of the brain and the biochemical mechanisms underlying oxidative stress mediated damage in brain during pathological states. Psycoactive drugs are metabolised by cytochrome P-450 in the liver into both active and inactive compounds, some of which can prolong the parent drug's therapeutic action. Dr. Ravindranath has demonstrated that P-450 enzymes are also present in the brain, where drug metabolism can take place, indicating that P-450 enzymes may play an important role in modifying the therapeutic action of drugs used in the treatment of mental illnesses at their primary sites of action in the brain. The presence of P-450 and FMO in neuronal cells and the inter-individual variations typically seen by her in the several human autopsy tissues, focuses attention for the first time on the role of in situ metabolism at the site of action of these drugs.
Dr. Ravindranath's pioneering research on the role of drug metabolism in human brain is a new area of research. It is highly relevant and will have a significant impact on the development of drugs used to treat mental illnesses. Oxidative stress has been implied in the pathogenesis and progression of a variety of neuro-degenerative disorders. However, very little understanding exists on the molecular events that regulates the recovery of brain from oxidative stress. Dr. Ravindranath has studied in great detail the response of brain to a variety of pathologic states that develop due to generation of oxidative stress. She has demonstrated the unique response of the brain to oxidative stress in terms of the protein Thiol modification, especially with respect to the electron transport chain components in the brain mitochondria. Importantly, she has shown that this may offer greater neuro-protection than traditional antioxidants such as vitamin E. Dr. Ravindranath's research has focussed on identifying newer aspects of brain functions other than those commonly studied such as neuro-tranmission and receptor interactions. Her research endeavours, which have not only been of great clinical relevance, but very successful as exemplified in the 1000 citations that her research papers have received so far. The pioneering work of Dr. Ravindranath has been recognised through the Shanti Swarup Bhatnagar Award in 1996. Her laboratory has also been recognised as an internationally pioneering laboratory in this area and she has been awarded a R-01 (individual investigator award) grant by National Institute of Mental Health (NIMH), National Institutes of Health, U.S.A. to pursue research in this area.
