ABSTRACT
The efflux of purine nucleobases and their nucleosides from the rat brain was investigated using the brain efflux index (BEI) method. Calculated BEI values showed that purine nucleobases had very rapid initial efflux after the intracerebral injection, which was followed by the slower efflux due to the intracellular trapping of labelled molecules and confirmed by the capillary depletion technique. The efflux of ribonucleosides was much slower than the efflux of nucleobases and the structure of the sugar moiety seemed to be important, since a significant difference in the efflux velocity between ribo- and deoxyribonucleosides was observed. The results of self- and cross-inhibition studies suggested that the efflux of test molecules was saturable and that purines shared the same transport system on the abluminal side of the blood-brain barrier.
Subject(s)
Blood-Brain Barrier/drug effects , Brain/drug effects , Carrier Proteins/drug effects , Purine Nucleosides/metabolism , Purines/metabolism , Adenosine/blood , Adenosine/cerebrospinal fluid , Animals , Blood-Brain Barrier/physiology , Brain/metabolism , Carbon Radioisotopes/metabolism , Carrier Proteins/physiology , Deoxyribonucleosides/blood , Deoxyribonucleosides/cerebrospinal fluid , Extracellular Space/drug effects , Extracellular Space/metabolism , Guanosine/blood , Guanosine/cerebrospinal fluid , Hypoxanthine/blood , Hypoxanthine/cerebrospinal fluid , Injections, Intraventricular , Inosine/blood , Inosine/cerebrospinal fluid , Purine Nucleosides/blood , Purine Nucleosides/cerebrospinal fluid , Rats , Rats, WistarABSTRACT
If febrile seizures cause significant compromise of neuronal metabolism (whether permanent or reversible), this should be reflected in an increase in the cerebrospinal fluid concentrations of neuron-specific enolase (NSE) and/or adenosine triphosphate (ATP) breakdown products. In the present study, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and NSE concentrations were determined in the cerebrospinal fluid of 90 children 1 h after febrile seizure (73 simple febrile seizures (SFS); 17 complex febrile seizures (CFS)), and in a control group of 160 children. There was no statistically significant difference between the SFS group and the control group for any of the substances determined, suggesting that SFS neither significantly depletes neuronal ATP concentration, nor significantly increases NSE concentration; thus, SFS do not appear to constitute a threat to neuronal integrity. However, patients with CFS showed significantly lower IMP concentrations and significantly higher adenine concentrations than controls, and significantly higher AMP concentrations than SFS patients; these results suggest that CFS may affect energy metabolism in the brain. However, NSE concentrations were normal in the cerebrospinal fluid of both SFS and CFS patients, suggesting that neither type of seizure causes significant neuronal damage, at least early after the seizure.
Subject(s)
Phosphopyruvate Hydratase/cerebrospinal fluid , Purine Nucleosides/cerebrospinal fluid , Purine Nucleotides/cerebrospinal fluid , Purines/cerebrospinal fluid , Seizures, Febrile/cerebrospinal fluid , Adenosine Monophosphate/cerebrospinal fluid , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Inosine Monophosphate/cerebrospinal fluid , Male , Reference Values , Seizures, Febrile/classification , Uric Acid/cerebrospinal fluidSubject(s)
Brain Chemistry , Extracellular Space/chemistry , Neurons/chemistry , Purine Nucleosides/analysis , Pyrimidine Nucleosides/analysis , Thalamic Nuclei/chemistry , Animals , Microdialysis/methods , Purine Nucleosides/cerebrospinal fluid , Purines/analysis , Purines/cerebrospinal fluid , Pyrimidine Nucleosides/cerebrospinal fluid , Pyrimidines/analysis , Pyrimidines/cerebrospinal fluid , RatsABSTRACT
The selective toxicity of purine deoxynucleoside to specific lymphocyte cell populations and recent evidence that purine nucleosides are important extracellular modulators of neurotransmission and coronary blood flow have prompted measurement of extracellular purines in man. By using a highly sensitive fluorimetric assay and collecting specimens into an inhibitor of adenosine deaminase, we have accurately measured purine nucleoside and hypoxanthine-xanthine levels in arterial and venous blood, in cerebrospinal fluid and in bone marrow aspirates. In peripheral venous plasma from normal volunteers, purine levels average 2.7 +/- 1.2 microM (mean +/- S.D.) with 38% in the form of adenosine and 47% as hypoxanthine and xanthine. Arterial purine levels are similar to those in mixed venous plasma; however, the hypoxanthine-xanthine component is reduced compared to simultaneously drawn mixed venous specimens (p less than 0.005). Hepatic venous plasma tends to have higher purine levels than does peripheral venous plasma (not significant), whereas bone marrow aspirates have 10-fold higher hypoxanthine-xanthine levels, suggesting that bone marrow may be a major source of plasma purines. Cerebrospinal fluid hypoxanthine-xanthine is twofold to eightfold higher than mixed venous levels, whereas adenosine levels are lower (p less than 0.01 and p less than 0.025, respectively).