Overexpression of kynurenic acid in stroke: An endogenous neuroprotector?

It is known that kynurenic acid (KYNA) exerts a neuroprotective effect against the neuronal loss induced by ischemia; acting as a scavenger, and exerting antioxidant action. In order to study the distribution of KYNA, a highly specific monoclonal antibody directed against KYNA was developed. This distribution was studied in control rats and in animals in which a middle cerebral artery occlusion (stroke model) was induced. By double immunohistochemistry, astrocytes containing KYNA and GFAP were exclusively found in the ipsilateral cerebral cortex and/or striatum, at 2, 5 and 21days after the induction of stroke. In control animals and in the contralateral side of the stroke animals, no immunoreactivity for KYNA was found. Under pathological conditions, the presence of KYNA is reported for the first time in the mammalian brain from early phases of stroke. The distribution of KYNA matches perfectly with the infarcted regions suggesting that, in stroke, this overexpressed molecule could be involved in neuroprotective/scavenger/antioxidant mechanisms.

NO-tryptophan: a new small molecule located in the rat brain.

A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms.

Direct visualization of retinoic acid in the rat hypothalamus: an immunohistochemical study.

In order to increase our knowledge about the distribution of vitamins in the mammalian brain, we have developed a highly specific antiserum directed against retinoic acid with good affinity (10(-8) M), as evaluated by ELISA tests. In the rat brain, no immunoreactive fibers containing retinoic acid were detected. Cell bodies containing retinoic acid were only found in the hypothalamus. This work reports the first visualization and the morphological characteristics of cell bodies containing retinoic acid in the mammalian paraventricular hypothalamic nucleus and in the dorsal perifornical region, using an indirect immunoperoxidase technique. The restricted distribution of retinoic acid in the rat brain suggests that this vitamin could be involved in very specific physiological mechanisms.

Circulating Antibodies to IDO/THO Pathway Metabolites in Alzheimer's Disease.

In Alzheimer's disease, indoleamine 2,3-dioxygenase and tryptophan hydroxylase are known to induce an overproduction of neurotoxic compounds, such as quinolinic acid and 3-hydroxykynurenine from the former, and 5-hydroxytryptophol and 5-methoxytryptophol from the latter. Other compounds, such as kynurenic acid, serotonin, and melatonin are produced via the same pathways. An improved ELISA method identified circulating antibodies directed against these compounds, linked to proteins, as previously described for other chronic diseases. This describes how only the A isotype of circulating immunoglobulins recognized a pattern of conjugated tryptophan metabolites in the sera of Alzheimer patients. These data indirectly confirmed the involvement of tryptophan derivatives in the pathogenic processes of Alzheimer's disease. Further studies are required to evaluate the relevance of these antibody patterns in monitoring this disease.

A confirmation study of Russian and Ukrainian data on effects of 2450 MHz microwave exposure on immunological processes and teratology in rats.

In a series of Russian and Ukrainian papers published from 1974-1986, it was reported that 30-day whole-body exposures to continuous-wave (CW) radiofrequency (RF) radiation at 2375 MHz and 5 W/m(2) disrupted the antigenic structure of rat brain tissue. The authors suggested that this action caused an autoimmune response in exposed animals. Moreover, these studies reported that blood serum from exposed rats injected into intact nonexposed female rats on the 10th day of pregnancy led to increased postimplantation embryo mortality and decreased fetus size and body weight. Because the results of these studies served in part as the basis for setting exposure limits in the former USSR, it was deemed necessary to perform confirmation studies, using modern dosimetric and biological methods. In our study, a new system was constructed to expose free-moving rats under far-field conditions. Whole-body and brain-averaged specific absorption rates (SARs) were calculated. All results, using ELISA and classic teratology end points, were negative in our laboratory. On the basis of this investigation, we conclude that, under these exposure conditions (2450 MHz, CW, 7 h/day, 30 days, 0.16 W/kg whole-body SAR), RF-radiation exposure had no influence on several immune and degenerative parameters or on prenatal development.

Vitamins in the monkey brain: An immunocytochemical study.

Using highly specific antisera directed against vitamins, the distribution of pyridoxal-, pyridoxine-, vitamin C- and nicotinamide-immunoreactive structures in the monkey (Macaca fascicularis) brain was studied. Neither immunoreactive structures containing pyridoxine or nicotinamide, nor immunoreactive fibers containing vitamin C were found in the monkey brain. However, this work reports the first visualization and the morphological characteristics of pyridoxal- and vitamin C-immunoreactive cell bodies in the mammalian central nervous system using an indirect immunoperoxidase technique. A high density of pyridoxal-immunoreactive cell bodies was found in the paraventricular hypothalamic nucleus and in the supraoptic nucleus and a low density of the same was observed in the periventricular hypothalamic region, whereas a moderate density of vitamin C-immunoreactive cell bodies was observed in the somatosensorial cortex (precentral gyrus). Immunoreactive fibers containing pyridoxal were only visualized in the anterior commissure. The restricted distribution of pyridoxal and vitamin C in the monkey brain suggests that both vitamins could be involved in very specific physiological mechanisms.

Evaluation of the effects of a new drug candidate (GEMSP) in a chronic EAE model.

Chronic Experimental Autoimmune Encephalomyelitis (EAE) was induced in rats to evaluate a new drug candidate (GEMSP) for the treatment of multiple sclerosis. This work is a part of preclinical studies on GEMSP, which is made up of fatty acids, vitamins and amino acids or their derivatives; all these compounds were linked to Poly-L-Lysine. In order to evaluate the effects of GEMSP, animals were divided into three experimental groups: 1) EAE rats treated with GEMSP; 2) EAE rats treated with NaCl; and 3) non-EAE rats. Using immunocytochemical techniques with a pan-leukocyte marker (anti-CD 45), differential leukocyte infiltration was compared in the central nervous systems of the different experimental groups. Antibodies directed against a component of GEMSP, the conjugated methionine, were used in all three groups. We found that: 1) GEMSP was effective in abolishing EAE. The crises and clinical scores were completely abolished in the animals of the first group, but not in the animals belonging to the second group; 2) the degree of leukocyte infiltration varied, depending on the different EAE stages, but was not related to the clinical score; and 3) after using anti-conjugated methionine antibodies, we observed immunoreactivity only in the motoneurons of the ventral horn of the spinal cord in the animals of the first group. This immunoreactivity was not found in the animals of the second or third groups. No methionine immunoreactivity was found in the brain. Our results suggest that GEMSP may be a potential drug candidate against the pathogenic processes involved in multiple sclerosis, inhibiting EAE episodes and brain leukocyte infiltration. Our results also show that one component of GEMSP, the methionine compound, is stored inside motoneurons. The possible physiological actions of GEMSP on spinal cord motoneurons are discussed.