Brain tissue hydrolysate, Cerebrolysin^®, acts on presynaptic adenosine receptors in the rat hippocampus

Abstract

Adenosine is a potent inhibitory modulator in the brain. It suppresses glutamatergic synaptic transmission and possibly acts as an endogenous brain neuroprotective agent. In this study we have examined the effects of a clinically used porcine brain tissue hydrolysate, Cerebrolysin^®, on synaptic transmission in the CA1 area of the rat hippocampus. Hippocampal slices were prepared for in vitro experiments using standard procedures and perfused with artificial cerebrospinal fluid at 32°C and pH = 7.4. Field potentials were evoked by stimulating the Schaffer collateral/commissural afferents and recorded in the stratum radiatum of CA1 field. Cerebrolysin^® or other pharmacological agents were dissolved in the perfusate prior to applications. The application periods were usually 5–15 minutes, sufficiently long to obtain steady state effects on synaptic transmission. A major effect of Cerebrolysin^® at 10 μl/ml was a depression of synaptic transmission at the Schaffer collateral/ commissural pathway. Detailed analysis showed that the inhibition is presynaptic and can be reduced by a specific blocker of Al adenosine receptors, 8-cyclopentyltheophylline (100nM). Since Cerebrolysin does not contain a detectable amount of adenosine, the effect on adenosine receptors must be indirect, perhaps by release of an endogenous agonist. This action of Cerebrolysin^® is consistent with the putative neuroprotective action underlying its clinical usage. Supported by EBEWE Initiative.