Measurement of prostaglandins in the cerebrospinal fluid in cat, dog, and man.

Prostaglandins are involved in the modulation of various central functions (neurotransmitters and hypothalamic hormone release, thermoregulation, cerebrovascular tone) and their levels increase in pathological situations [subarachnoid hemorrhage (SAH), stroke, convulsive disorders, etc.]. This study, using sensitive and specific antibodies, examined levels of four eicosanoids, prostaglandins E2 and F2 alpha (PGE2, PGF2 alpha); and the metabolites of PGI2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and of thromboxane A2, thromboxane B2 (TxB2), in the cerebrospinal fluid (CSF) obtained atraumatically from three species (human, canine, and feline). An assessment of the methodologic procedures (extraction and radioimmunoassay) was carried out. Human lumbar cerebrospinal fluid was shown to contain PGF2 alpha (15-44 pg/ml), 6-keto-PGF1 alpha (undetectable to 39 pg/ml), and TxB2 (undetectable to 28 pg/ml), whereas PGE2 was undetectable (less than 18 pg) in all cases. In both animals species the eicosanoid concentrations were 3- to 30-fold higher than humans for every prostaglandin examined. Although the prostaglandin profile for a given species remained constant (cat, PGE2:6-keto-PGF1 alpha:TxB2:PGF2 alpha; dog, TxB2:PGE2:6-keto-PGF1 alpha:PGF2 alpha), the absolute levels were found to be lower in the pentobarbital-anesthetized animals than in conscious cats. The correspondence of the prostaglandin profiles found in cerebrospinal fluid with the profiles reported in the literature in brain homogenates for the same species supports the hypothesis that cerebrospinal fluid levels of prostaglandins reflect the relative rates of synthesis in neural tissue.

Prostaglandin levels in cerebrospinal fluid from multiple sclerosis patients in remission and relapse.

Radioimmunoassay (RIA) techniques have been employed to determine prostaglandin (PG) levels in the cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients in remission and relapse and in subjects with other neurological diseases (OND). PGE and PGF2 alpha concentrations in spinal fluid from MS patients in relapse were significantly lower than values estimated during remission and in individuals with OND of the central nervous system (CNS). These observations are discussed in relation to the clinical state of patients with demyelinating disease together with a consideration of the concept that disordered immune mechanisms contribute a central role in the pathogenesis of MS.

Cerebrospinal fluid prostaglandin F2 alpha in stroke patients: no relationship to the degree of neurological deficit.

The concentration of prostaglandin F2 alpha (PGF2 alpha) was measured in cerebrospinal fluid (CSF) of 50 patients with recent stroke divided into three groups in respect to the time (up to 24 h) that expired between cerebrovascular insult and CSF sampling. 10 of the additionally studied persons were neurologically normal (control group). None of the investigated subjects were undergoing any therapy at the time of CSF sampling. The estimation of the neurological score revealed that the stroke patients suffered from acute cerebral ischemic attacks of varying severity. No relationship between the CSF PGF2 alpha and neurological status was found. Within the first 4 h after the stroke a marked increase in PGF2 alpha was found, afterwards being diminished but still enhanced in comparison to the controls.

[New contributions on extinction tests of essential headache. II. The test with indoprofen]. / Nuovi contributi su le prove di estinzione nelle cefalee essenziali: II) Il test con indoprofene.

The authors described the results about the action of indoprofen (i.v. 400 mg) in three subjects affected by premenstrual migraine. They showed decreased levels of PGF2 alpha in the cerebrospinal fluid evaluated by gas-chromatography and mass spectrometry. The samples were extracted at 0, 15, 30 and 45 minutes. The levels of pain, was also decreased, they were evaluated by the analogic visual scale (V.A.S.).

[New contributions on extinction tests of essential headache. III. The test with tiapride]. / Nuovi contributi su le prove di estinzione nelle cefalee essenziali: III) Il test con tiapride.

The Authors valued effects of the extinction-test with Thiapride (200 mg i.v.) in the primary headaches. They particularly noticed a significant reduction of PGF2-alpha and PRL, together with an increase of 5-HT and beta-ELI in CSF.

Effects of subarachnoid haemorrhage on intracranial prostaglandins.

Prostaglandins E2, F2 alpha, 6 oxo F1 alpha and thromboxane B2 increased in cisternal CSF following mock subarachnoid haemorrhage in dogs, particularly PGE2 (X25.5). Concentrations were increased also in lumbar CSF of five patients some 8 days after subarachnoid haemorrhage. Subarachnoid haemorrhage did not alter the production of prostaglandins by dog whole cortex or choroid plexuses in vitro, but production by pooled dissected cerebral arteries of PGE2 was increased and of 6 oxo F1 alpha was decreased. Intravenous indomethacin decreased prostaglandin production by cerebral tissues, and caused a marked decrease in the prostacyclin metabolite in CSF. The implications of our findings for the aetiology of cerebral vasospasm are discussed.

Prostaglandin F2 alpha concentrations in the cerebrospinal fluid of children with febrile convulsions, epilepsy and meningitis.

Cerebrospinal fluid prostaglandin F2 alpha (CSF PGF2 alpha) levels were measured by radioimmunoassay in children as follows: Febrile convulsions (31 cases), epilepsies (32 cases), meningitides (31 cases) and non-neurological diseases (20 cases), totaling 114 cases. A 4.5-fold increase in CSF PGF2 alpha levels was seen in simple febrile convulsion, and a 2.5-fold increase in those with complex febrile convulsion as compared to those with non-neurological diseases. On the other hand, no increase in CSF PGF2 alpha levels was seen in children with epilepsy. When the body temperature was normal, the mean CSF PGF2 alpha levels showed no relation with age. When the body temperature was between 37.5 degrees C and 40 degrees C, the CSF PGF2 alpha levels in infants were higher than those in older children. The CSF PGF2 alpha levels in children with meningitis were high. The mean CSF PGF2 alpha levels in bacterial meningitis were not statistically (p greater than 0.05) different from those in viral meningitis. The CSF PGF2 alpha levels in meningitis were high on admission and gradually decreased with therapy. The results of our studies indicate that PGF2 alpha of the central nervous system markedly increased in infants and children with febrile convulsions or meningitis but not in those with epilepsy.

GC/MS analysis of prostaglandins in ventricular cerebrospinal fluid from head injured humans.

The purpose of this study was to determine the levels of prostaglandins in ventricular cerebrospinal fluid (CSF) from severely head injured humans on successive days following injury. Sixteen samples from three patients were purified using XAD-2 and high pressure liquid chromatography and PGE2, PGF2alpha, and 6-keto-PGF1alpha were quantitated utilizing deuterated internal standards and gas chromatography-mass spectrometry. Generally, the levels of PGs in ventricular CSF were found to be higher than has previously been reported for PGs in CSF from spinal taps. PG levels ranged from reported for PGs in CSF from spinal taps. PG levels ranged from nondetectable to 11.8, 3.3 and 27.3 ng per ml for PGE2, PGF2alpha, and 6-keto-PGF2alpha, respectively. However, in one sample, PG levels were much higher than this range and approached the levels found in human cortical tissue. Analysis of red and white blood cell numbers in the CSF showed no relationship between cell numbers and prostaglandin levels. This study confirms a previous report that 6-keto-PGF2alpha is the major prostaglandin in CSF and demonstrates that PG levels in ventricular CSF from head traumatized humans can be greatly elevated.

Prostaglandin F2 alpha levels in human cerebrospinal fluid in normal and pathological conditions.

Prostaglandin F2 alpha concentrations in cerebrospinal fluid (CSF) from normal human subjects and patients with various pathological disorders of the central nervous system (CNS) were measured by radioimmunoassay. The mean PGF2 alpha level in 54 controls with no evidence of organic CNS disease was 67 pg/ml (range: 25-150 pg/ml). A significant increase of PGF2 alpha levels was demonstrated in most samples from patients with CNS diseases. Extremely high values were found in patients with stroke and subarachnoid hemorrhage when samples were collected shortly after the cerebral attack. With the regression of clinical symptoms and radiological findings a decrease of PGF2 alpha levels was demonstrated in this group of patients. In 32 patients with cerebral transient ischemic attacks a mean PGF2 alpha concentration of 170 pg/ml (range: 35-355 pg/ml) was found. Increased PGF2 alpha levels were found in patients with epilepsy when samples were collected within a few days after a convulsion. PGF2 alpha levels of four patients with slow progredient forms of multiple sclerosis without clinical symptoms at the time of sample collection were not different from normal controls while the mean PGF2 alpha level of all other patients with multiple sclerosis was 152 pg/ml (range: 55-325 pg/ml). Moreover, increased values could be demonstrated in patients with cerebral tumors and inflammatory processes.

Determination of prostaglandin F2 alpha, E2, D2 and 6-keto-F1 alpha in human cerebrospinal fluid.

Prostaglandin (PG)F2 alpha, E2, D2 and 6-keto-F1 ALha were determined in human cerebrospinal fluid by a mass spectrometric technique. The samples were obtained from 12 patients with suspected intracranial disease. A 64 fold variation in PG levels was observed. The major PG was 6-keto-F1 alpha (0.12--15 ng/ml). PGF2 alpha and PGE2 were present in lower concentrations PGD2 was below the level of detection (0.05 ng/ml) except in one patient with extremely high total levels of PGs.

Levels and disappearance of prostaglandin F2alpha in cerebral spinal fluid: a clinical and experimental study.

The concentration of prostaglandin F2alpha (PGF2alpha) was measured in cerebrospinal fluid (CSF) obtained by lumbar puncture in patients with subarachnoid hemorrhage and compared to control values. The level of this prostaglandin was elevated at some time in most patients during the course of their illness. However, this could not be correlated with the severity of neurological deficits observed. The possibility that the concentration of PGF2alpha in lumbar fluid may not reflect that present intracranially was tested experimentally in anesthetized dogs. In these experiments only a small fraction of the radioactive PGF2alpha injected into the cisterna magna appeared in lumbar CSF. Prostaglandin F2alpha rapidly disappeared from the cisterna magna, half time 8 minutes, and radioactivity was present in blood from the jugular vein indicating that normally this prostaglandin rapidly egresses from the CSF into blood. These findings suggest that PGF2alpha can be rapidly transported away from the brain. This could explain the low concentrations of PGF2alpha in CSF of normal individuals and in some patients who have severe cerebral vasospasm. Conversely, the elevation of PGF2alpha in lumbar CSF noted in some patients might be due, in part, to an impairment of transport caused by the size and location of the hemorrhage.

Prostaglandins. A review of neurophysiology and psychiatric implications.

This article reviews the function of prostaglandins (PGs) in the nervous system and discusses the possible alterations in PG metabolism as relating to mental illness. The PGs are a unique group of cyclic fatty acids whose immediate precursors are thought to function postsynaptically by inhibition or facillitation of neurotransmission through cyclase inhibition or activation, and by means of a negative feedback loop to inhibit further release of neurotransmitter from the presynaptic nerve. A review of PGs in psychiatric conditions is presented as well as a discussion of the interaction of psychoactive drugs with the PGs. The concluding section of this review discusses possible future strategies to provide insight into PG physiology as it relates to synaptic transmission in normal and pathological conditions in man.

Measurement of prostaglandin F2alpha levels in cerebrospinal fluid of febrile and afebrile patients with advanced cancer.

Prostaglandin F2alpha levels were measured by radioimmunoassay in 95 samples of unextracted human cerebrospinal fluid obtained from 73 patients with advanced cancer. Concentrations of PGE were too low to be reliably determined by this method using the commercially available kits. Forty-six of the samples assayed contained less than 25pg/ml PGF2alpha. The remaining levels ranged from 25 to 1154 pg/ml c.s.f.; the majority contained less than 200pg/ml. A possible correlation was found between elevated c.s.f. granulocyte count and increased PGF2alpha. A similar relationship was found with regard to protein. These studies failed to demonstrate a correlation between elevated levels of PGF2alpha in cerebrospinal fluid and any pathophysiologic condition.