Stroke Patients after repetitive Transcranial Magnetic Stimulation (rTMS)–Alterations of Tryptophan Metabolites in the Serum

Abstract

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.

Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

“…50 Importantly, enhanced KYNA levels were also observed in human cerebrospinal fluid, 51 and accumulated data strongly suggest a correlation between increased KYNA levels and age-related neurodegenerative disorders. [17][18][19][20][21][22][23] Although the present study doesn't support the assumption of a correlation between neurodegeneration and the impairment of mitochondria caused by KYNA, it is important to note that an enhancement of kynurenine aminotransferase activities in the brain may increase the formation of XAN from 3-OH-KYN, as well. In the presence of XAN, the RC value of brain mitochondria was significantly lowered, since oxygen consumption during the passive state was slightly increased, whereas oxygen consumption during the active state was moderately lowered in the presence of glutamate/malate.…”

“…Therefore, one could argue that the physiological significance of these in vitro model experiments for the in vivo situation could be questionable. It is important to mention that submicromolar endogenous levels of L-TRP metabolite, as reported by our studies 18,[21][22][23]51 and several others 3,17,20,25,43 do not take into account that concentration found in homogenate of whole tissue could be significantly lower than in vivo concentrations in compartments of their synthesis, eg, mitochondria.…”

“…40 Increased levels of ANA were observed in the periphery and CNS in various pathological conditions. 23,31 Another metabolite of L-TRP, 3-OH-KYN, which has a role in toxic processes, 5 markedly affected the mitochondrial activities of all three investigated organs. RC values were reduced significantly by 3-OH-KYN in brain, liver and heart mitochondria, independently of whether glutamate/malate or succinate was used.…”

“…The metabolism of L-TRP via kynurenine is overactivated under various pathological conditions as can be seen in the CNS or serum of HIV-1 infected patients, [20][21][22] stroke patients, 23,31 picorna virus encephalomyocarditis, 71 and particularly in neuroborreliosis (personal observation).…”

Jerusalem Balsam Lowers Kynurenic Acid Formation: An In Vitro Study

“…KYNA is altered significantly in various neuropsychiatric and immunologic disorders [6][7][8] and also in aging process [9]. Alterations of L-TRP metabolite levels in the blood found immediately after strokes indicate a significant activation of metabolism along the kynurenine pathway and increase the cardiovascular risk factor, as well [10][11][12]. In the line, we found that KYNA lowers the efficacy of mitochondria ATP synthesis of heart mitochondria [13,14].The aim of the study was to examine the Jerusalem Balsam action, whether this "natural mixture" has an ability to influence KYNA synthesis in the rat liver tissue, in an in vitro study.…”