**2.3.2 Development**

In this research, it has been studied the concentration of Ca, Mg, Zn, Cu, Fe and Mn in CSF in order to analyze their influence on the pathogeny of some neuropathies (González-Romarís et al., 2011).

The mineral chemical elements and the trace elements were analysed in the CSF extracted from 37 people (17 men and 20 women, between 27 and 73 years of age) who were considered to be healthy after performing a clinical and analytical study. They made up the control group.

In the review of results for 2008 (results not published), the values for ALA-D in the adult sample were 60.59 ± 16.49 (x ± SD), higher than those obtained in 1990: 46.81 ± 15.45 (x ± SD), which is logical if we take into account the fact that the activity of ALA-D in erythrocytes has a negative or inverse correlation with respect to the concentration of Pb in blood. In the 1990 study, Pearson's coefficient of linear correlation obtained was: r = -0.568

**2.3 Study of some elements in cerebrospinal fluid: physiopathological evaluation** 

This study, still in progress, can serve as an example of using the atomic absorption spectrometry technique for the assistance, together with other techniques, in the clinical

The cerebrospinal fluid (CSF) fills the subarachnoid space between the arachnoid membranes and the pia mater called leptomeninges which protect the Central Nervous System -CNS- (encephalon and spinal cord). Seventy percent of the CSF is formed in secretory structures called choroid plexi and the remaining 30% is produced from the

Although the composition of CSF is similar to a plasma filtrate, there are differences which indicate that the CSF formed is produced both by a process of filtration and by active secretion, an osmotic balance being observed between CSF and plasma. A similarity can be seen in the composition of CSF and the extracellular liquid of the nervous system, indicating an easy interchange between both compartments. The CSF and in the cerebral interstice are separated from the blood circulation by the hematoencephalic and hematocephalorachideal barriers which prevent the free passing of substances. This is why they are considered to be functional elements of protection of the nerve cells (Nolte, 1994). In comparison with plasma, the CSF contains a greater concentration of Na, Cl and Mg and a lower one of glucose, proteins, amino acids, uric acid, K, bicarbonate, Ca and phosphate (Guyton, 1990). These differences indicate that the CSF is produced by a mechanism of active secretion and varies according to the location of CSF extraction with regard to the structures it bathes.

Water passes from the stroma to the CSF following the concentration gradient produced by the ATPase-dependent carrier proteins, Cl, Ca and Mg (Nolte, 1994). Cellular metabolytes

The CSF maintains an appropriate chemical environment for neurotransmission and

In this research, it has been studied the concentration of Ca, Mg, Zn, Cu, Fe and Mn in CSF in order to analyze their influence on the pathogeny of some neuropathies (González-

The mineral chemical elements and the trace elements were analysed in the CSF extracted from 37 people (17 men and 20 women, between 27 and 73 years of age) who were considered to be healthy after performing a clinical and analytical study. They made up the control group.

also enter the extracellular liquid from neurones and glial cells.

removes metabolic products and substances which are harmful for the CNS.

(p<0.001).

diagnosis of some diseases.

cerebral capillaries (Carpenter, 1985).

**2.3.1 Introduction** 

**2.3.2 Development** 

Romarís et al., 2011).

In addition, analysis was made of the CSF of 136 individuals from the Services of Neurology, Neurosurgery and Emergency. The CSF was extracted by lumbar puncture in all cases.

The analysis of Ca, Mg, Zn, Cu, Fe and Mn was performed by flame atomic absorption using the corresponding hollow cathode for each metal. The wavelengths for the reading of the absorbance corresponding to each cation analysed were the indicated by the manufacturer.

The values (mean and standard deviation) obtained in the control group for each metal analysed were as follows: Ca (mg/dL), 4.95 ± 0.70; Mg (mg/dL), 2.74 ± 0.10; Zn (µg/dL), 17.40 ± 7.50; Cu (µg/dL), 15.70 ± 4.50; Fe (µg/dL), 13.10 ± 3.60; and Mn (µg/dL), 2.50 ± 0.70. These values agree with the findings published by other authors (Hazell, 1997; Kapaki et al., 1997; Levine et al., 1996).

With regard to the results obtained in the pathological CSF, significant increases were found (p<0.05) in the concentrations of Ca, Cu, Fe, Zn and Mn in the groups classified with cell and protein increase in CSF in comparison to the control group. It was also see that the significant increase of the Ca, Zn and Cu concentrations is greater in those groups which present a higher concentration of proteins, while the increase of Mn corresponds to the increase of cell count. With regard to magnesium, it was seen that the significant reduction of its concentration in relation to the control group corresponds equally both if the cell count or the protein concentration was increased.

Interest in analysing these metals in CSF is directed to explaining the pathogenesis of some dysfunctions of the CNS. Clinical and experimental studies reviewed in the literature confirm the influence that these metals have on the pathogeny of some CNS dysfunctions and diverse neuropathies.

In this way the Ca and Mg ions play an important role in the action of glutamate, which is one of the most important neurotransmitter of vertebrates in the brain. The receptor of glutamate N-methyl-D-aspartate (NMDA) can only be activated in certain conditions of depolarisation of the membrane (Johnson & Ascher, 1988). The Mg ion blocks the channel, not being permeable to the Ca ions**.** When the receptor of glutamate are activated, the receptor reduces its affinity for Mg and the channel becomes permeable, permitting the entry of Ca ions to the neurone, a phenomenon which has been related to memory and the learning process (Hammond & Tritsch, 1990; Thomson, 1986). A reduction has been found in the glutamate and Mg concentration in the CSF in schizophrenic patients (Levine et al., 1996).

Some studies have found an increase of Cu in serum and CSF and an increase of Mn in the spinal cord in Amyotrophic Lateral Sclerosis (ALS), which suggests that this metal plays a role in the pathogeny of this disease (Kapaki et al., 1997).

The clinical association of Pb poisoning and ALS with an increase of Pb in blood and bone has been reported (Kamel et al., 2006). It has been suggested that patients with polymorphism in the gene of the ALA-D enzyme might be more at risk of presenting ALS in exposure to Pb (Kamel et al., 2003). Other studies have found no association between exposure to metals and ALS (McGuire et al., 1997; Bergomi et al., 2002).

It has been suggested that, regarding Mn, the binding of this metal in the basal ganglions of the brain may contribute in the pathogeny of the symptomatology of hepatic encephalopathy (Kuliseusky & Puyols, 1992; Weissenborn, 1995; Noremberg, 1998).

Atomic Absorption Spectroscopy: Fundamentals and Applications in Medicine 21

aragonese population.

**4. References** 

d. Metals in cerebrospinal fluid (Ca, Mg, Zn, Cu, Fe and Mn):

pathogenesis of some brain conditions.

proteins. *Rev. Esp. Fisiol.* 1985; 41: 145-150.

*Neurochem.* 1992; 58: 730-735.

1974; 12: 389-390.

study. *Environ. Res.* 2002; 89: 116-23.

Buenos Aires: El Ateneo, 1985, 1-19.

*Res.* 1988; 16: 1229-1230.

Cartón, JA. Saturnismo. *Med. Clin. (Barc)* 1988; 91: 538-540.

tissues. *Endocrinology* 1965; 77: 1151-1154.

York: Academic Press, 1967; 17-31.

plasmático en rata. *Rev. Esp. Fisiol.* 1990; 46(2): 139- 146.

the Rat. *Proc. Soc. Exp. Biol., N.Y.,* 1956; 92(4): 859-863.



Alda, JO. & Escanero, JF. Transport of calcium, magnesium and strontium by human serum

Aschner, M. & Gannon, M. Manganese uptake and efflux in cultured rat astrocytes. *J.* 

Barbosa, F.; Tanus-Santos, JE.; Gerlach, RF. & Parsons, PJ. A Critical Review of Biomarkers

Bergomi, M.; Vinceti, M.; Nacci, G.; Pietrini, V. & Bratter, P. Environmental exposure to trace

Berlin, A. & Schaller, KH. European Standardized Method for the determination of delta-

Berlin, A.; Schaller, KH.; Grimes, H.; Langevin, M. & Trotter J. Environmental exposure to

Campbell, BC.; Brodie, MJ.; Thompson, GG.; Meredith, PA.; Moore, R. & Goldberg, A.

Carpenter, MB. Neuroanatomía Humana de Strong y Edwin (5ª Edición, 2ª reimpresión).

Castellano, MaC.; Soteras, F.; Córdova, A.; Elósegui, LMa. & Escanero, JF. Zinc distribution

Córdova, A.; Soteras, V.; del Villar, V.; Elósegui, LMa. & Escanero, JF. Efecto de la

Chausmer, AB.; Weiss, P. & Wallach, S. Effect of thyrocalcitonin on calcium exchange in rat

Comar, CL. In: "Strontium metabolism", Leniham, JMA; Loutit, JF; Martin, JH. Eds. New

Comar, CL.; Wasserman, RH.; & Nold, MM. Strontium-Calcium Discrimination Factors in

Escanero, JF. Inferencia del estroncio en el metabolismo del calcio. Tesis Doctoral.

Departamento de Fisiología. Facultad de Medicina. Universidad de Zaragoza, 1974.

Cartón, JA. Saturnismo: epidemiología y diagnóstico. *Med. Clin. (Barc)* 1985; 84: 492-499.

Future Needs. *Environ. Health Perspect.* 2005; 113(12): 1669–1674.

determination. *Int. Arch. Occup. Environ. Health* 1977; 39: 135-141.

and acute hepatic porphyria. *Clin. Sci. Mol. Med.* 1977; 53: 335-340.

Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and

elements and risk of amyotrophic lateral sclerosis: a population-based control

amino-levulinic acid dehydratase activity in blood. *Z. Klin. Chem. Klin. Biochem.* 

lead: analytical and epidemiological investigations using the European Standardized Method for blood delta-amino-levulinic acid dehydratase activity

Alterations in the activity of the enzymes of haem biosynthesis in lead poisoning

between protein serum ligands in rats: acute and chronic overload of zinc. *Med. Sci.* 

tiroparatiroidectomía, la parathormona y la calcitonina sobre el estroncio

Moreover, it has been demonstrated that Mn reduces the uptake of glutamate in cultivated astrocytes. The great capacity of astrocytes to accumulate Mn suggests that its uptake by these cells may play an important role in the development of Alzheimer's type II astrocytosis (Hazell, 1997; Aschner & Gannon, 1992).

In conclusion, this research line, still in progress, can be highly promising to clarify the pathogenesis of some brain conditions.
