Brain tumor as a prototype of severe brain lesion in patients with "low T3 syndrome".

The purpose of our study was to contribute to better understanding of cerebrospinal fluid (CSF) as a valuable biological material in the research of brain tumors within the "low T3 syndrome", and to discuss the role of thyroid hormones in the central nervous system in subjects with severe cerebral lesions. We studied the levels of total triiodothyronine (tT3), total thyroxine (tT4), free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3) and thyrotropin (TSH) in serum, and fT3, fT4, rT3 and TSH levels in CSF of patients with brain tumor, and compared the results with control group. Study results indicated a statistically significantly higher level of rT3 in serum and CSF of brain tumor patients vs. control group (p < 0.05). The rT3/fT3 ratio was highest in CSF and serum of brain tumor patients, yielding a statistically significant difference (p < 0.05). These results could suggest higher permeability of the blood-brain barrier in brain tumor patients. We also assume that rT3, in the framework of"cerebral low T3 syndrome", is also generated through local intracerebral conversion. Disruption of this process in severe cerebral lesion can lead to increased rT3 concentrations, i.e. development of the "low T3 syndrome".

Photoperiod modulates access of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) to the brain and its effect on gonadotropin and thyroid hormones in adult ewes.

The effects of photoperiod on the cerebrospinal fluid (CSF) concentration of six ortho-substituted polychlorinated biphenyls (PCBs: PCB28, PCB52, PCB101, PCB138, PCB153, and PCB180), the effects of an orally administered low dose of PCB153 (0.3mg/kg, three times a week for three weeks) on PCBs and thyroid hormones (THs) concentrations in the CSF and plasma, and the release of luteinizing hormone (LH) were determined in ovariectomized, estradiol-implanted ewes (2.5 years old) maintained indoors under artificial long day (LD, 16L: 8D) and short day (SD, 8L: 16D) conditions. Concentrations of two PCBs (PCB28 and PCB153) in the plasma and four PCBs in the CSF (PCB101, PCB138, PCB153, and PCB180) were significantly higher during LD than SD. Following PCB153 treatment, its concentration in the plasma was higher in SD (1.2 ± 0.3 ng/ml) than LD (0.2 ± 0.05 ng/ml), but similar in the CSF (10.2 ± 3.7 pg/ml vs. 13 ± 0.7 pg/ml) under both photoperiods. During SD, the concentration of PCB153 in the CSF was higher in treated animals than controls, while no differences were noted under LD. These findings indicate that in ewes, exposure of the brain to more highly chlorinated, ortho-substituted PCBs may be modulated by photoperiod. PCB153 treatment had no effect on plasma THs, but reduced total triiodothyronine concentration during LD and free thyroxine during SD in the CSF. Under both photoperiods, PCB153 reduced basal plasma LH and reinforced the inhibition of pulsatile LH release during LD. As PCB153 reduced LH and THs (which are involved in the seasonal control of reproduction in ewes), it may have a braking effect on seasonal transitions between active and inactive phases of reproduction.

Impaired hepatic function and central dopaminergic denervation in a rodent model of Parkinson's disease: a self-perpetuating crosstalk?

In Parkinson's disease (PD), aside from the central lesion, involvement of visceral organs has been proposed as part of the complex clinical picture of the disease. The issue is still poorly understood and relatively unexplored. In this study we used a classic rodent model of nigrostriatal degeneration, induced by the intrastriatal injection of 6-hydroxydopamine (6-OHDA), to investigate whether and how a PD-like central dopaminergic denervation may influence hepatic functions. Rats received an intrastriatal injection of 6-OHDA or saline (sham), and blood, cerebrospinal fluid, liver and brain samples were obtained for up to 8 weeks after surgery. Specimens were analyzed for changes in cytokine and thyroid hormone levels, as well as liver mitochondrial alterations. Hepatic mitochondria isolated from animals bearing extended nigrostriatal lesion displayed increased ROS production, while membrane potential (ΔΨ) and ATP production were significantly decreased. Reduced ATP production correlated with nigral neuronal loss. Thyroid hormone levels were significantly increased in serum of PD rats compared to sham animals while steady expression of selected cytokines was detected in all groups. Hepatic enzyme functions were comparable in all animals. Our study indicates for the first time that in a rodent model of PD, hepatic mitochondria dysfunctions arise as a consequence of nigrostriatal degeneration, and that thyroid hormone represents a key interface in this CNS-liver interaction. Liver plays a fundamental detoxifying function and a better understanding of PD-related hepatic mitochondrial alterations, which might further promote neurodegeneration, may represent an important step for the development of novel therapeutic strategies.

Neurochemical measures co-vary with personality traits: forensic psychiatric findings replicated in a general population sample.

Neurobiological markers in cerebrospinal fluid (CSF) and in serum, previously found to co-vary with destructive personality traits in violent offenders, were explored in a general population sample of 21 patients undergoing knee surgery. Results on the Karolinska Scales of Personality (KSP) and the Temperament and Character Inventory (TCI) were compared with CSF/serum albumin ratios and serum concentrations of beta-trace protein (betaTP) (as markers for blood-brain barrier (BBB) permeability), to CSF/serum albumin ratios between the dopamine and serotonin metabolites homovanillic acid (HVA)/5-hydroxyindoleacetic acid (HIAA) and to CSF and serum ratios between activated thyroid hormone (T3) and its precursor T4. Serum betaTP concentrations correlated with CSF/serum albumin ratios (P=0.018), but not with preoperative serum creatinine concentrations. Serum betaTP correlated significantly with Monotony Avoidance and Impulsiveness; CSF HVA/5-HIAA ratios with Irritability and low Cooperativeness. The betaTP is a potential serum marker for the integrity of the BBB that does not necessitate lumbar puncture. Thyroid hormones did not correlate with personality traits. As reported in forensic psychiatric patients, aggressive, unempathic personality traits were thus associated with increased dopaminergic activity in relation to the serotonergic activity and impulsivity to increased BBB permeability also in a general population group.

Association between thyroid hormone levels and monoaminergic neurotransmission during surgery.

BACKGROUND: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. METHODS: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. RESULTS: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T(3)/T(4) ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T(3)/T(4) ratio decreased (p<0.0001), while the CSF T(3)/T(4) ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T(3) and T(4) at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. CONCLUSIONS: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress.

Central metabolic messengers and the effects of nutrition on gonadotrophin secretion in sheep.

Nutrition influences the reproductive axis via alteration of gonadotrophin secretion. However, a link between nutrition and the secretion of GnRH, which drives the axis, has yet to be established. The aim of the present study was to measure the change in the concentrations of metabolic substances in the cerebrospinal fluid of adult male sheep offered a diet designed to maintain constant gonadotrophin secretion (Group M; n = 6), or a diet known to increase gonadotrophin secretion (Group M + L; n = 6). On days 1, 3 and 10 of the dietary treatments, cerebrospinal fluid and jugular blood were sampled and analysed for metabolic fuels (glucose, amino acids and free fatty acids) and metabolic hormones (insulin, insulin-like growth factor I, GH, prolactin, cortisol and the thyroid hormones). On day 11 of the dietary treatment, LH pulse frequency and mean FSH concentrations in Group M + L had increased relative to Group M and to day 0. Plasma concentrations of prolactin and insulin on days 3 and 10, and glucose and insulin-like growth factor I on day 10, were higher in Group M + L than in Group M, but only cerebrospinal fluid concentrations of insulin, glucose and certain amino acids were affected by the dietary treatments on days 3 and 10. Cerebrospinal fluid, but not plasma, concentrations of aspartate, tyrosine, cystine, phenylalanine and arginine on day 3, and glutamine, gamma-aminobutyric acid, threonine, alanine on days 3 and 10, were higher in Group M + L relative to Group M. On day 10, plasma and cerebrospinal fluid concentrations of arginine, phenylalaine, proline, tyrosine, methionine and phosphoserine, but only the plasma concentrations of linoleic acid, aspartate and serine, were higher in Group M + L than in Group M. Concentrations of triiodothyronine, thyroxine, and cortisol in plasma and cerebrospinal fluid were not affected. These results show that the nutritional stimulation of gonadotrophin secretion is accompanied primarily by fluctuations in plasma and cerebrospinal fluid concentrations of insulin and certain amino acids, which suggests that, when nutritional status is improved, insulin, amino acids and possibly glucose interact to modulate GnRH secretion.

Neuroendocrinology of cerebrospinal fluid: peptides, steroids, and other hormones.

Cerebrospinal fluid (CSF) has been implicated as a conduit in neuroendocrine integration. Evidence suggests that the ventricular CSF may promote the central distribution, enable the dilutional inactivation (sink effect), and facilitate the peripheral delivery of neurally secreted hormones. This discussion of the sites of origin and concentration gradients of CSF hormones and of both physiological and pharmacological variations in the hormonal content of the CSF provides insight into the putative role of CSF in neuroendocrine regulation. Normal or control concentrations of peptides, steroids, and other hormones present in human lumbar CSF are listed to provide a physiological base line to which the CSF hormonal profile of patients may be compared. The individual, somatotopic, chronological, endocrinological, pharmacological, and possible artifactual variations in CSF hormonal composition are presented to facilitate the formulation of clinical protocols and to eliminate possible sources of error.