Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases (KAT) I and II. A host of immune mediators influence tryptophan degradation. In the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a group of human subjects aged between 25 and 74 years were determined by using a high performance liquid chromatography method. In CSF and serum KAT I and II activities were investigated by radioenzymatic assay, and the levels of β₂-microglobulin, a marker for cellular immune activation, were determined by ELISA. The correlations between neurochemical and biological parameters were evaluated. Two subject groups with significantly different ages, i.e. <50 years and >50 years, p < 0.001, showed statistically significantly different CSF KYNA levels, i.e. 2.84 ± 0.16 fmol/µl vs. 4.09 ± 0.14 fmol/µl, p < 0.001, respectively; but this difference was not seen in serum samples. Interestingly, KYNA is synthesised in CSF principally by KAT I and not KAT II, however no relationship was found between enzyme activity and ageing. A positive relationship between CSF KYNA levels and age of subjects indicates a 95% probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA levels significantly correlated with IgG and β₂-microglobulin levels (R = 0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was found between other biological parameters in CSF or serum. In summary, a positive relationship between the CSF KYNA level and ageing was found, and the data would suggest age-dependent increase of kynurenine metabolism in the CNS. An enhancement of CSF IgG and β₂-microglobulin levels would suggest an activation of the immune system during ageing. Increased KYNA metabolism may be involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic neurotransmission in the ageing CNS.

Repetitive transcranial magnetic stimulation (rTMS) as a new non-invasive painless procedure has been tested for augmentation of motor performance and reduction of spasticity in post-stroke patients. Stroke patients (N = 34) were recruited for rTMS treatment and brain activity analysis (EEG) was performed before and after rTMS. The effect of rTMS was evaluated using National Institute of Health Stroke Scale (NIHSS), Barthel -Index and Ashworth Scale. The content of L-tryptophan (L-TRP), L-kynurenine (L-KYN), kynurenic acid (KYNA) and anthranilic acid (ANA) was determined in the serum of stroke patients before the 1st, after the 5th and after 10th rTMS application using high performance liquid chromatography. In a separate experiment, L-TRP metabolites were determined in the serum of an independent group of stroke patients (N=47) and control subjects (N = 6). The content of L-TRP and L-TRP metabolites in the serum of stroke patients was significantly increased, L-TRY was 121% of CO; L-KYN 161% of CO, p<0.015; ANA 280 % of CO, p<0.001; KYNA 243% of CO, p<0.001, compared to control subjects. Similar changes were found in stroke patients recruited for rTMS. After the 10th rTMS treatment L-KYN and ANA levels increased moderately but significantly in the serum and it was L-KYN 107%, p<0.01; ANA 110%, p = 0.055, versus the value before 1st rTMS, respectively. The ratios L-KYN/TRP and ANA/KYNA increased moderately but significantly after the 10th rTMS. Creatin kinase and prolactin levels were in normal range during rTMS. Stroke patients treated with rTMS have shown a significant enhancement of motor performance and moderate reduction of spasticity. The alteration of ANA/KYNA ratio after rTMS might be of significance with respect to the clinical improvement of patients. The present study gives favour for rTMS as a means for neurorehabilitation of patients after stroke. Notable, the management of therapies following rTMS are of importance for an improvement of hand and fingers activities, as observed within this study.

A female 49 years old patient with vestibular schwannoma developed normal pressure hydrocephalus. Patient complained about gait disturbance, urinary incontinence and memory impairment. Investigation of clinical parameter and measurement of kynurenic acid in the cerebrospinal fluid (CSF) and serum in patients with normal pressure hydrocephalus and in corresponding controls (CO; N=15) were performed. Within investigated parameters significant increase of protein and IgG levels in CSF were found in patient with normal pressure hydrocephalus. Furthermore, kynurenic acid was increased in the CSF by 60% and in the serum by 40%, comparing to CO subjects. Kynurenic acid level in CO was in the CSF and serum 2.77 ± 0.23 and 53.4 ± 4.0 nM, respectively. Three lumbar punctures were applied to patient with normal pressure hydrocephalus and clinical parameters partially normalized and lowering of kynurenic acid levels in CSF and serum were observed. Patient was improving after each lumbar puncture but the effect was transient, therefore permanent CSF shunting was recommended. After that a complete remission of symptoms occurred. Revealed data indicate a significant advantage of single punctures in management of treatment for normal pressure hydrocephalus. Increase of kynurenic acid in CSF represents interesting parameter. It is questionable if occurrence of cognition impairment and/or dementia in patients with normal pressure hydrocephalus might be related to an enhancement of kynurenic acid in the CNS.

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