'Smelling' the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus.

The olfactory-type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G-protein (Gαolf), adenylate cyclase 3 and cyclic nucleotide-gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP-brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration-dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gαolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C-inositol 1,4,5-trisphosphate pathways. Olfactory-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.

Central nervous system damage during cardiac surgery assessed by 3 different biochemical markers in cerebrospinal fluid.

Three cerebral biochemical markers, adenylate kinase (AK), neuron-specific enolase (NSE) and protein S-100, were determined in the cerebrospinal fluid (CSF) of male patients 24 h after coronary artery bypass grafting to investigate the extent of possible center nervous system (CNS) damage and relation to the type of oxygenator and the use of an arterial line filter. The patients were randomized into three groups for extracorporeal circulation (ECC); bubble oxygenator without an arterial line filter (Group I, n = 30), bubble oxygenator with a filter (Group II, n = 29) and a flat-sheet membrane oxygenator without a filter (Group III, n = 33). Pathologically high CSF levels of AK and NSE were found 24 h after ECC in respectively 93% and 95% of the patients. All protein S-100 concentrations were within the normal range. Isolated high CSF concentrations of AK, NSE and protein S-100 were observed in group I. Levels of AK and NSE were the lowest in group III, although there was no statistical difference between the groups. In conclusion, our study suggested that CNS damage caused by ECC involved neurons rather than glial cells. AK and NSE in the CSF seemed to be markers of ischaemic neuronal damage. Postoperative levels of biochemical markers in the CSF tended to be the lowest in the flat-sheet membrane oxygenator group.

CSF cyclic AMP and CSF adenylate kinase in cerebral ischaemic infarction.

The severity of neurological deficits, size of hypodense zone on CT, concentration of cAMP and activity of adenylate kinase in cerebrospinal fluid (CSF) were evaluated at predefined intervals in the acute stage of supratentorial cerebral ischaemic infarction in 52 patients. Patients with cerebral infarction had raised activities of adenylate kinase CSF as compared with normal persons. Patients with marked neurological deficits, only slight improvement of neurological signs and large infarction zones on CT had higher average activities of adenylate kinase and lower concentration of cAMP in CSF. Alterations of CSF adenylate kinase and CSF cAMP values were most distinct on the 3rd day after the stroke. Reasons for the changes may be metabolic disorders following brain ischaemia.

Dementia--and adenylate kinase activity in cerebrospinal fluid.

Adenylate kinase (AK) was determined in a lumbo-cisternal cerebrospinal fluid (CSF) gradient and in CSF from patients with mental deterioration. AK activity was unchanged in the gradient and different from albumin and albumin ratio (alb CSF/albumin serum), a blood-brain barrier marker in the same gradient. No differences between normal pressure hydrocephalus, multiinfarct dementia and dementia of the Alzheimer type could be found with regard to adenylate kinase activity in CSF.

Phosphodiesterase and adenyl-cyclase activities in the cerebral cotex of the aging rat.

In an effort to determine the factors responsible for the four-fold decrease in cyclic-AMP content of the rat cerebral cortex, observed to occur between the ages of 3 and 6 months, studies were performed on adenyl-cyclase and phosphodiesterase, the cyclic-AMP synthesizing and hydrolyzing enzymes. The activities and kinetic characteristics were determined for both enzymes as obtained from the cerebral cortex of rats ranging in age from one to 24 months. No age dependence was observed either in adenyl-cyclase activity, assayed with or without fluoride ion, or in phosphodiesterase activity. It was concluded that age related changes in factors other than the direc levels of these enzymes underlie the age related decline in cortical cyclic-AMP levels.