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VOL. 74 (3), 387-408, 2008 FINE TUNING NEUROMODULATION BY ADENOSINE...

the local control over microcirculation and necessary oxygen,
rendering membrane potentials useless to modulate neuronal
function. The fact that chemical mediators are already part
of normal physiology, whether during development or adulthood,
means that their activity can be modified by specific agonists and
antagonists to restore homeostasis or to promote the safe pathways
that can lead to regeneration. During the past decades considerable
experimental and clinical data have been accumulated regarding
cellular and biochemical events associated with neuroprotection,
neuroregeneration and brain repair.

Three situations related to neuroprotection will be discussed in
the context of adenosine-related medicines as therapeutical potential
agents. The points I shall emphasize are: first, the insults of neurons
caused by hypoxia/ischemia, which is a typical situation that occurs
during stroke; secondly, I will discuss the reactive oxygen species
(ROS) as a way to induce lesions in neurons and its relation to
neurodegenerative diseases and thirdly, how to enhance the putatitve
neuroprotective actions contained in neurotrophic factors, such as
e.g. the brain derived neurotrophic factor (BDNF) and the glial
derived neurotrophic factor (GDNF).

Before I go into these aspects I would like to give you briefly
some biographical notes about my research context that can explain
why a medical doctor graduated in 1965, who wishes to be a
psychiatrist enters into basic neuroscience research. In fact, when in
1957 I started my studies on Philosophy and in particular Psychology,
I was fascinated by Perception and in particular Behaviour. Why
that strange behaviour of the main character, Meursault of the Albert
Camus novel «L’Etranger»? I decided to go into the medical school
to become a Psychiatrist. It was indeed with great joy that in 1977
when the first edition of the book From Neuron to Brain by Stephen
Kuffler and John Nichols appear, I read in the preface: «We work
mostly on the machinary that enables neurons to function. Students
who become interested in the nervous system almost always tell us that
their curiosity stems from a desire to understand perception,
consciousness, behaviour, or other higher functions of the brain.
Knowing of our preoccupation with the workings of isolated nerve cells
or simple cell systems, they are frequently surprised that we ourselves
started with similar motivations, and they are even more surprised that

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