Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: a potential novel treatment target for perinatal asphyxia.

Worldwide, perinatal asphyxia is an important cause of morbidity and mortality among term-born children. Overactivation of the N-methyl-D-aspartate receptor (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia-ischemia, but the role of both endogenous NMDAr co-agonists D-serine and glycine remains largely elusive. We investigated D-serine and glycine concentration changes in rat glioma cells, subjected to oxygen and glucose deprivation (OGD) and CSF from piglets exposed to hypoxia-ischemia by occlusion of both carotid arteries and hypoxia. We illustrated these findings with analyses of cerebrospinal fluid (CSF) from human newborns affected by perinatal asphyxia. Extracellular concentrations of glycine and D-serine were markedly increased in rat glioma cells exposed to OGD, presumably through increased synthesis from L-serine. Upon reperfusion glycine concentrations normalized and D-serine concentrations were significantly lowered. The in vivo studies corroborated the finding of initially elevated and then normalizing concentrations of glycine and decreased D-serine concentrations upon reperfusion These significant increases of both endogenous NMDAr co-agonists in combination with elevated glutamate concentrations, as induced by global cerebral ischemia, are bound to lead to massive NMDAr activation, excitotoxicity and neuronal damage. Influencing these NMDAr co-agonist concentrations provides an interesting treatment target for this common, devastating and currently poorly treatable condition.

Adenylate kinase activity in the cerebrospinal fluid of hypoxic newborns.

Adenylate kinase (AK) activity in the cerebrospinal fluid (CSF), described as a marker of brain edema and lesions in adults, was studied in 79 newborns with severe respiratory distress within 24 h after admission to the Intensive Care Unit (ICU). The CSF-AK activity was compared with CSF lactate concentration, CSF lactate dehydrogenase activity (LDH), and CSF and serum creatine kinase isoenzyme BB (CK-BB) activity. Newborns were divided into Group I with moderate to severe brain dysfunction and Group II with mild or no detectable brain dysfunction on discharge from the ICU. Mean CSF-AK activity (11.31 U/L) in Group I was significantly (p less than 0.001) higher than in Group II (2.82 U/L). Correlation between CSF-AK and CSF lactate was r = 0.714, p less than 0.01 and between CSF-AK activity and CSF-LDH activity was r = 0.550, p less than 0.01 in Group I. Preliminary data indicate that CSF-AK activity within 24 h after ischaemia is an indicator of hypoxic brain lesions in newborns. Its prognostic value for the infant's development remains to be determined by further study.

Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome.

Infants with respiratory distress syndrome are routinely evaluated for infection which commonly includes a lumbar puncture. In this study cerebrospinal fluid (CSF) examination failed to elicit evidence for meningitis in 238 consecutively admitted infants with respiratory distress syndrome evaluated during the first 24 hours of life. Blood cultures were obtained in all; suprapubic or catheterized urine was obtained in 163 infants; CSF was collected successfully in 203 infants. Seventeen infants demonstrated positive blood cultures: 7 Streptococcus, 5 Staphylococcus, 3 Haemophilus influenzae, 1 Bacillus subtilis and 1 diphtheroid infection. CSF obtained from 14 of those infants had normal examinations and sterile cultures. Factors associated with bacteremia were birth weight (P less than 0.01), gestational age (P less than 0.01), prolonged rupture of membranes (P less than 0.05) and leukopenia below 10 000/mm3 (P less than 0.05). In view of the negative CSF examinations in infants with positive blood cultures and the potential complications of lumbar puncture (hypoxia, trauma, infection, epidermoid tumor), the potential risks of CSF evaluation may exceed the assessed benefit for the infant with respiratory distress syndrome.

Levels of 6-ketoprostaglandin F1 alpha in neonatal cerebrospinal fluid.

6-Ketoprostaglandin F1 alpha determinations were made by radioimmunoassay on samples of cerebrospinal fluid from 41 neonates. Levels were below the smallest quantity detectable (50 pg/ml) in 29 and greater than 200 pg/ml in only 3 babies. These results suggest that 6-ketoprostaglandin F1 alpha is not a major prostaglandin in the cerebrospinal fluid of human infants.