Cerebrospinal fluid functions

Effects In Humans. Neither postmortem nor functional cerebrospinal fluid (CSF) studies in humans provide firm evidence for similar, long-term damages or alterations to monoaminergic neurons in chronic stimulant abusers. In part, the lack of demonstrable neurochemical changes may well be due to the obvious preclusion of well-controlled prospective experimentation in humans, as well as to variability in critical variables (e.g., individual sensitivity or pattern of abuse) encountered in clinical research. Possible relationship of the various complications of stimulant abuse including hyperpyrexia, seizure, anoxia, and metabolic exhaustion to neuronal chromatolysis, terminal destruction, and monoamine and enzymatic depletion have not been systematically explored in human autopsy eases. It should be also noted that, under nonperturbed conditions, overt behavioral deficits are rare in... 

Roy, A., Pickar, D., Dejong, J., Karoum, F. Linnoila, M. (1998). Norepinephrine and its metabolites in cerebrospinal fluid, plasma and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression. Arch. Gen. Psychiatry, 45, 849-57. 

Embedded within the brain are four ventricles or chambers that form a continuous fluid-filled system. In the roof of each of these ventricles is a network of capillaries referred to as the choroid plexus. It is from the choroid plexuses of the two lateral ventricles (one in each cerebral hemisphere) that cerebrospinal fluid (CSF) is primarily derived. Due to the presence of the blood-brain barrier, the selective transport processes of the choroid plexus determine the composition of the CSF. Therefore, the composition of the CSF is markedly different from the composition of the plasma. However, the CSF is in equilibrium with the interstitial fluid of the brain and contributes to the maintenance of a consistent chemical environment for neurons, which serves to optimize their function. 

Tricoire, H., Moller, M., Chemineau, P. 8r Malpaux, B. (2003). Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod. Reprod. Suppl. 61, 311-21. 

Serotonergic function has been investigated by using multiple methods. Assaying the major metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) has been widely used (Ch. 13). This method assumes that CSF 5-HIAA is related to brain serotonin activity. This premise is supported by the rostral-caudal concentration gradient of CSF 5-HIAA and the observation in postmortem studies that CSF 5-HIAA correlates with levels of 5-HIAA in prefrontal cortex [16], both of which suggest that CSF 5-HIAA is a reasonable index of prefrontal serotonin turnover. ... 

Medical indications Chronic pulmonary disease (excluding asthma) chronic cardiovascular diseases, diabetes mellitus chronic liver diseases, including liver disease as a result of alcohol abuse (e.g., cirrhosis) chronic alcoholism, chronic renal failure or nephrotic syndrome functional or anatomic asplenia (e.g, sickle cell disease or splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery]) immunosuppressive conditions and cochlear implants and cerebrospinal fluid leaks. Vaccinate as close to HIV diagnosis as possible. 

Mass spectrometry has been applied mainly in proteome research, but also in discovery and quantitation of neuropeptides that are involved in pain mechanisms, such as nocistatin, substance P, or verification of, for example, the structure of endogenous morphine in the central nervous system. Some proteomics studies of pain are aimed at the search for pain markers in cerebrospinal fluid, as it may reflect changes in brain and spinal cord functioning. Another research area concerns proteome analysis in cancer pain using spinal cord tissue and animal models. 

An important function of cerebrospinal fluid is mechanical, supporting the brain and cushioning it from blows to the cranium. It also provides another means of removing unwanted substances from the brain, including any neurotransmitters or metabolites that have leaked from synapses. 

The central adrenergic system. It is only recently that immunohistochemical methods have been developed to show that adrenaline-containing cells occur in the brain. Some of these cells are located in the lateral tegmental area, while others are found in the dorsal medulla. Axons from these cells innervate the hypothalamus, the locus coeruleus and the dorsal motor nucleus of the vagus nerve. While the precise function of adrenergic system within the brain is uncertain, it may be surmized that adrenaline could play a role in endocrine regulation and in the central control of blood pressure. There is evidence that the concentration of this amine in cerebrospinal fluid... 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Thus when the results of the studies on platelets, lymphocytes, changes in cerebrospinal fluid metabolites of brain monoamines and the post-mortem studies are taken into account it may be concluded that a major abnormality in both noradrenergic and serotonergic function occurs in depression, and that such changes could be causally related to the disease process. 

Absorption/Distribution - Pyrazinamide is well absorbed from the Gl tract and attains peak plasma concentrations within 2 hours. It is widely distributed in body tissues and fluids including the liver, lungs, and cerebrospinal fluid. Pyrizinamide is approximately 10% bound to plasma proteins. Metabolism/Excretion - The half-life is 9 to 10 hours it may be prolonged in patients with impaired renal or hepatic function. 

Although the examination of total protein in cerebrospinal fluid is quite valuable, it is necessary to mention that this parameter does not provide exact information on the function of the blood-CSF barrier. This is easy to understand. The increased concentration of total protein in cerebrospinal fluid can be based both on the failure of the barrier with a subsequent increase in the concentration of albumin and of other proteins originating from serum and on a more significant intrathecal synthesis of immunoglobulins, especially in levels of IgG. 

The albumin quotient is the most precise, routinely used criterion for assessment of the function of the blood-CSF barrier because albumin in cerebrospinal fluid originates exclusively from serum. Its parallel determination during the monitoring of any CSF protein is necessary because this is the only way to differentiate its increased concentration in cerebrospinal fluid due to passive penetration of the respective serum protein from a more specific increase in the concentration of the monitored protein. It is based on its intrathecal synthesis or on a specific transport mechanism for the given protein across the blood-CSF barrier. Unfortunately, some clinicians disregard this recommendation, and this elementary fact is not sufficiently emphasized in publications on cerebrospinal fluid (A22). 

During the monitoring of any protein in cerebrospinal fluid, it is necessary to bear in mind the functional status of the blood-CSF barrier, serum concentration of the respective protein, and the dimensions of the molecule (or the information based on the molecular weight). These data principally influence the resulting concentration in cerebrospinal fluid. It must also be emphasized again that the parallel determination of albumin in cerebrospinal fluid and serum is necessary. 

Stourac, R, Differential diagnostic relevance of the blood-CSE barrier function and oligoclonal IgG synthesis in cerebrospinal fluid in multiple sclerosis. Clin. Biochem. Metab. 6(27), 210-212 (1998). 

For infected sites that are difficult to reach, i.e. the cerebrospinal fluid, higher than usual doses should be administered, or the drug should be injected directly in the site of the infection (e.g. intrathe-cally). Abnormal body composition and impaired renal function may warrant dosage modification for effectiveness but also to limit toxicity. 

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