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J. A. RIBEIRO AN. R. ACAD. NAC. FARM.

NGF administration, in the acute, post-traumatic period following
fluid-percussion brain injury, apparently improves post-traumatic
cognitive deficits (39) and a neurotrophic factor treatment following
traumatic brain injury is neuroprotective (16). Brain-derived
neurotrophic factor (BDNF) has been shown to be neuroprotective
in models of excitotoxicity, axotomy and cerebral ischemia. Blaha
et al. (3) demonstrated the therapeutic potential of brain-derived
neurotrophic factor following traumatic brain injury in the rat.
Neurotrophic factors are involved in neuronal maturation during
development, and protect neurons in experimental models of
neurodegenerative diseases. However, because of the blood brain
barrier it is very difficult to deliver these factors into the brain. A way
to overcome this difficulty was implemented by (38) using trial
infusions of nerve growth factor (NGF) in three patients with
Alzheimer’s disease. NGF was infused continuously through a
neurosurgically implanted cannula into the lateral ventricles of
the brain (38). However, technical difficulties discouraged the
continuation of this therapy.

BDNF is a neurotrophin abundant in the brain and recently it
has been shown that BDNF applied acutely facilitates synaptic
transmission if, before its application one depolarises the preparation
with potassium (4). Also in hippocampal synaptosomes BDNF
facilitates potassium-evoked glutamate release providing
synaptosomes have been previously depolarised by potassium (5).

Another group (17) showed that A2A receptors induce
phosphorylation of BDNF-TrkB-receptors. Since depolarisation
enhances the release of adenosine our group (see 9) decided to
investigate if activating A2A receptors we could selectively facilitate
BDNF actions on synaptic transmission. In fact with the activation
of A2A receptors with selective agonists or by increasing the adenosine
production in the brain with adenosine kinase inhibitors (e.g.
iodotubercidin), it is possible to induce facilitatory effects of BDNF
on synaptic transmission in hippocampal slices (see Figure 1). In
non-A2A pre-conditioned slices there is no BDNF effect on synaptic
transmission (9). It therefore appears to exist potential for the use of
A2A agonists or substances such as adenosine kinase inhibitors, which
through peripheral administration could wake up «sleeping»
neurotrophic factors in order to induce neuroprotection. This is also

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