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

relatively safe treatment. Recently it has been shown in vitro patch
clamp studies that in conditions of 32 ºC, adenosine inhibits NMDA
receptor currents in hypoxia suggesting that adenosine might exert
neuroprotection during hypothermia (34).

In summary, during hypoxia the neuroprotection induced by
adenosine operates both a decrease of neurotransmitter release
via inhibition of pre-synaptic calcium entry by blocking calcium
channels (28) and post-synaptically inhibiting calcium entry via
inhibition of NMDA-receptors.

Finally I also would like to mention our recent observations on
stimulation with interleukin-6 (IL-6), which increases A1 receptor-
mediated inhibition of synaptic transmission. In WT but not in IL6-
KO mice, seizures induce adenosine A1 receptor expression. These
observations reinforce the role of adenosine as an anti-epileptic
agent. IL-6-induced amplification of A1 receptor function enhances
the responses to readily released adenosine during hypoxia, enables
neuronal rescue from glutamate-induced death, and protects animals
from chemically induced convulsing seizures. Taken together, these
results suggest that IL-6 minimizes the consequences of excitotoxic
episodes on brain function through the enhancement of endogenous
adenosinergic signaling (see 2).

REACTIVE OXYGEN SPECIES (ROS)

During brain insults with xanthine-xanthine oxidase there is
production of reactive oxygen species (ROS). It was described by
Almeida et al (1) that the synaptic inhibition induced by ROS needs
adenosine to completely recover in contrast with what happens in
the presence of adenosine A1 receptor blockade with DPCPX (1).

ENHANCEMENT OF NEUROPROTECTIVE EFFECTS OF
NEUROTROPHIC FACTORS

Neurotrophic factors have been shown to have potential
therapeutic applications in neurodegenerative diseases, and nerve
growth factor (NGF) is neuroprotective in models of excitotoxicity.

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