ASSESSMENT AND COMPARISON OF HORMONAL IMMUNOEXPRESSION AND THE CLINICAL PICTURE IN PATIENTS WITH PITUITARY ADENOMAS.

INTRODUCTION: Symptoms related to hypersecretion of hormones in patients with pituitary adenomas do not always correlate with immunohistochemical staining results. OBJECTIVE: To evaluate the relationship between the pituitary adenomas hormone immunoexpressions and endocrine presentations. PATIENTS AND METHODS: The clinical status and immunoexpression of 72 patients who underwent transsphenoidal surgery for pituitary adenomas were analyzed. RESULTS: Macroadenomas were diagnosed in 51 cases (70.84%), while microadenomas were found in 21 cases (29.16%). The 72 adenoma specimens were divided into 22 monohormonal, 21 plurihormonal, 21 immunonegative and 8 unreliable specimens. The positive immunohistochemical staining results occurred as follows: prolactin and growth hormone 25% each, adrenocorticotropic hormone 13.89%, thyroid-stimulating hormone 5.56%, leuteinizing hormone and follicle-stimulating hormone 12.5%, glycoprotein hormone alpha-subunit 22.22%. Statistically significant relationships between the immunohistochemical presentation and the preoperative diagnosis were found for prolactin and hyperprolactinemia, growth hormone and acromegaly and adrenocorticotropic hormone and Cushing's syndrome. CONCLUSIONS: The lack of full concordance between the clinical presentations and immunohistochemical staining was mainly a result of the presence of nonfunctioning adenomas, plurihormonal adenomas and unreliable specimens. The morphometric method introduced in this study, utilizing the immunoexpression index, provided a very precise evaluation of pituitary adenomas pathology.

Diagnosis of ovarian tumour tissues by SR-FTIR spectroscopy: A pilot study.

Ovarian cancer is the seventh most common cancer among women across the world with very high mortality rates. Histology is considered the gold standard for tumour diagnosis. FTIR spectroscopy is relies on registering biochemical differences in the samples analysed, including biological specimens. Therefore, the Synchrotron radiation based-Fourier transform infrared spectroscopy (SR-FTIR) was used for the preliminary investigation of the molecular composition of the human, non-fixed ovarian neoplastic tissues with different type of biological potential. The study that was carried out on thin tissue sections, placed on barium fluoride infrared windows, was focused on investigating spatial distribution of the biochemical markers in various ovarian tumours. Since the structural constituents of tissues accumulate different molecules which may correspond to the specific type of ovarian tumours, the main goal of this study was to check if the mean intensities of the spectral lines of some bio-molecules can be treated as ovarian cancer bio-indicators. Moreover, an attempt to identify and understand the underlying biochemical changes associated with the disease was carried out. The major spectral differences in the frequency and intensities were identified as bonds of lipids, protein massif and nucleic acids. The results obtained suggest that Fourier transform infrared spectroscopy can be used as a supporting tool in the analysis of neoplastic ovarian tissue.

Intraepidermal nerve fiber density in vulvar lichen sclerosus and normal vulvar tissues.

Lichen sclerosus (LS) is a chronic and inflammatory disease causing sensory symptoms such as itch and pain and affecting most frequently genital skin of women. Intraepidermal nerve fiber density (IENFD) was examined immunohistologically in 20 vulvar skin biopsies of patients affected by LS and in 20 control vulvar skin biopsies, in order to determine if these sensory sensations originate in changes in the epidermal innervation. Obtained results show fewer protein gene product 9.5 (PGP 9.5) positive intraepidermal nerve fibers (IENF) in LS tissues compared to controls (P = 0.004), while the number of calcitonin gene-related peptide (CGRP) positive IENF in LS was increased compared to normal vulvar tissue (P = 0.03). No differences in the number of vasoactive intestinal peptide (VIP) expressing IENF could be observed. To our best knowledge, this is the first study to describe intraepidermal nerve fiber density in vulvar LS. Significant differences in IENFD between LS and control skin samples, which have been found, point to the damage to the small nerve fibers in the disease process of LS, which may contribute to pathogenesis of LS sensory symptoms.

Quantification of selected elements in ovarian tumours and their potentials as a tissue classifier.

Neoplastic and healthy ovarian tissues were analysed to identify the changes in the spatial distribution and concentration of elements using synchrotron induced micro X-ray fluorescence spectroscopy. High-resolution distribution maps of minor and trace elements were drawn. Significant amounts of elements such as P, S, Cl, K, Ca, Fe, Cu, Zn, Br and Rb were present in all neoplastic tissues analysed. The study showed significant diversifications in elemental distributions depending on the structure of tissue. The efficacy of micro X-ray fluorescence spectroscopy to distinguish between various types of ovarian tumours based on the concentrations of studied elements was confirmed by multivariate discriminant analysis. Our analysis showed that the most important elements for tissue classification are S, Cl, K, Fe, Zn, Br and Rb.

Combined in-situ imaging of structural organization and elemental composition of substantia nigra neurons in the elderly.

Human dopaminergic system in general, and substantia nigra (SN) neurons, in particular, are implicated in the pathologies underlying the human brain aging. The interplay between aberrations in the structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress. In the present study, we demonstrate an integrated approach to the analysis of the structural organization, assembly, and metals' accumulation in two distinct areas of SN: in the neuromelanin neurons and neuropil. By using the highly brilliant source of PETRA III and the Kirkpatrick-Baez nano-focus, large area histological brain slices are scanned at the sub-neuronal resolution, taking advantage of continuous motor movement and reduced acquisition time. Elemental analysis with synchrotron radiation based X-ray Fluorescence (SRXRF) is combined with X-ray Phase Contrast Imaging (XPCI) to correct for inherent aberrations in the samples' density and thickness, often referred to as the mass thickness effect. Based on the raw SRXRF spectra, we observed the accumulation of P, S, Cl, K, Ca, Fe, Cu and Zn predominantly in the SN neurons. However, upon the mass thickness correction, the distributions of Cl became significantly more uniform. Simultaneously with the fluorescence signal, the Small Angle X-ray Scattering (SAXS) is recorded by a pixel detector positioned in the far-field, enabling fast online computation of the darkfield and differential phase contrast (DPC). The data has demonstrated the SN neurons and neuropil produces excellent contrast which is due to their different mass density and scattering strength, indicative of differences in local structure and assembly therein. In all, the results show that combined SRXRF-XPCI-SAXS experiments can robustly serve as a unique tool for understanding the interplay between the chemical composition and structural organization that may drive the biochemical age-related processes occurring in the human dopaminergic system.

Shulman disease (eosinophilic fasciitis) in X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) diagnosed in the first year of life is an immunodeficiency with a life-long indication for substitution of immunoglobulins, due to lack of B lymphocytes in the periphery. The decrease of bacterial infection frequency and severity is an effect of immunoglobulin replacement. However, in the majority of patients bronchiectasis and chronic sinusitis with an overgrown mucous membrane develop despite regular substitution. Autoimmune diseases as co-existing diseases in XLA are noted in a few patients presenting symptoms associated with arthritis, scleroderma and myositis. Our patient was diagnosed with XLA in the first year of life, followed by regular substitution of immunoglobulins. The symptoms of pain, edema of muscles of the right shank with skin edema and discoloration after mild injury were noted in a 13-year-old boy. Shulman disease was diagnosed after 6 months of symptoms, based on histopathology of muscle and skin biopsy. Before the diagnosis, non-steroid anti-inflammatory drugs (NSAID) were used with a transient effect. After the diagnosis, therapy included steroids, immunoglobulins in a high dose and immunosuppression, with improvement of clinical symptoms. During methotrexate (MTX) therapy the patient developed two episodes of pneumonia, so mycophenolate mofetil (MMF) was used, with a similar effect. Now, with this therapy, the symptoms are mild and stable without progression.

Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus.

BACKGROUND: Disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on MRI were described as a prognostic factor for responsiveness to the treatment of idiopathic normal pressure hydrocephalus (iNPH). Our premise is that DESH could be associated with compression of the cerebral white matter. Microstructural changes can be identified using diffusion tensor imaging (DTI), specifically fractional anisotropy (FA). The aim of this study is to compare FA in iNPH patients with and without DESH and healthy controls. METHODS: We analysed 1.5-T MRI scans of patients fulfilling the criteria of probable or possible iNPH and positive supplementary tests before and after surgery (ventriculo-peritoneal shunt). FA was measured in the anterior and posterior limb of the internal capsule (PLIC) and in the corpus callosum. Patients were divided into the DESH and non-DESH group. These data were also compared to FA values in the control group. RESULTS: Twenty-seven patients and 24 healthy controls were enrolled. DESH was present in 15 patients and lacking in 12. Twenty-three iNPH patients were shunt responders (85.2 %), and 4 were non-responders (14.8 %). All patients in the DESH group were shunt responders. In the non-DESH group, eight patients were responders (66.7 %). A significant difference between the DESH and non-DESH group was found in the FA of the PLIC. The mean value of FA in the PLIC was 0.72 in the DESH group and 0.66 in the non-DESH group. After the surgery FA decreased in both groups. In the DESH iNPH group FA PLIC decreased to 0.65 and in the non-DESH iNPH group to 0.60. In the healthy controls, the mean FA in the PLIC was 0.58. CONCLUSION: DESH on MRI scans is related to a higher FA in the PLIC with a decrease after the surgery. It reflects a more severe compression of the white matter than in non-DESH patients or healthy volunteers. DESH patients had better outcome than non-DESH patients. This study confirmed the importance of DESH as a supportive sign for iNPH.

Angiocentric glioma from a perspective of A-B-C classification of epilepsy associated tumors.

Angiocentric glioma (AG) is a newly-classified, very rare, WHO grade I central nervous system (CNS) lesion, occurring usually in children and young adults. Only 52 patients with AG have been reported so far, making it one of the rarest neuropathological entities. Hereby we present two new cases of AG in young subjects with detailed neuropathological investigations and a neuroradiological picture along with a brief summary of all already published literature reports of this tumor. Histopathological examination of the resected tissue from both cases revealed similar changes characteristic of AG. The tumors were composed of spindle-like, elongated cells, forming characteristic pseudorosettes around vessels and diffusively infiltrating surrounding tissue, trapping neurons between tumor cells. Noticeably, some neoplastic cells encrusting vessels extended far beyond the main tumor mass. Hypothetically, this may be responsible for the recurrence of the tumor even in the case of apparently total excision. In immunohistochemistry, AG cells were glial fibrillary acidic protein (GFAP) and vimentin positive, also exhibiting a strikingly significant epithelial membrane antigen (EMA) dot-like staining pattern. In one of the cases, electron microscopy revealed ependymal differentiation features such as microvilli and cilia. Taken together, all these data strongly confirm a dual astroglial-ependymal nature of the tumor. Follow up corroborates benign character of this neoplasm. Both AGs reported here were immunonegative for the product of the mutated IDH-1 gene what, according to our best knowledge, has never been reported so far. It may suggest that in their pathogenesis AGs differ from grade II astrocytomas, which in most cases harbor a mutation of IDH-1. Noteworthy, neuroimaging in our cases was relatively characteristic but not conclusive, therefore biopsy (at least) is mandatory. A newly proposed so called "A-B-C" classification of long-term epilepsy-associated tumors (LEATs) places AG in a category named ANET. The authors shortly review the A-B-C classification of LEATs.

Expression of dmrt1 and vtg genes during gonad formation, differentiation and early maturation in cultured Russian sturgeon Acipenser gueldenstaedtii.

Expression of the dmrt1 and vtg genes was described using the real-time PCR (rt-PCR) method from 25 to 1600 days post-hatch (dph) in cultured Russian sturgeon Acipenser gueldenstaedtii. The level of dmrt1 transcription in gonads in subsequent studied periods increased exponentially while vtg expression increased in gonads and livers of A. gueldenstaedtii examined, but in later stages of development. Both dmrt1 and vtg genes showed elevated expression in intersex individuals probably caused by dietary exposure to phyto-oestrogens.

Endplate calcification and cervical intervertebral disc degeneration: the role of endplate marrow contact channel occlusion.

BACKGROUND: The aim of this study was to determine the fundamental relationships between cervical intervertebral disc (IVD) degeneration, endplate calcification, and the patency of endplate marrow contact channels (MCC). MATERIALS AND METHODS: Sixty cervical IVDs were excised from 30 human cadavers. After sectioning the specimens underwent micro computed tomography (microCT) - from all images the number, calibre, diameter and distribution of endplate openings were measured using ImageJ. Next, the specimens were scored for macroscopic degeneration (Thompson's classification), and subsequently underwent histological analysis for both IVD and endplate degeneration (Boos's classification) and calcification. RESULTS: The study group comprised 30 female and 30 male IVDs (mean age ± SD: 51.4 ± 19.5). Specimen's age, macroscopic and microscopic degeneration correlated negatively with the number of MCCs (r = -0.33-(-0.95); p < 0.0001), apart from the MCCs > 300 µm in diameter (r = 0.66-0.79; p < 0.0001). The negative relationship was strongest for the MCCs 10-50 µm in diameter. CONCLUSIONS: There is a strong negative correlation between the number of endplate MCCs, and both macroscopic and microscopic cervical IVD and endplate degeneration. This could further support the thesis that endplate calcification, through the occlusion of MCCs, leads to a fall in nutrient transport to the IVD, and subsequently causes its degeneration.

The combination of artificial neural networks and synchrotron radiation-based infrared micro-spectroscopy for a study on the protein composition of human glial tumors.

Protein-related changes associated with the development of human brain gliomas are of increasing interest in modern neuro-oncology. It is due to the fact that they might make some of these tumors highly aggressive and difficult to treat. This paper presents a methodology for protein-based analysis of human brain gliomas using synchrotron radiation based Fourier transform infrared spectroscopy (SRFTIR) coupled with artificial neural networks (ANNs). The main goal of this study was to optimize a set of ANNs to predict the secondary structure of proteins (alpha-helices, beta-sheets, beta-turns, bends, random coils) in brain gliomas, based on the amide I-II spectral range. All networks were tested and optimized to reach the standard error of prediction (SEP) lower than 5%. The results indicate that protein-related changes are associated with a tumor's malignancy grade. Particularly, the content of alpha helices increases with increasing malignancy grade, while the content of beta sheets decreases. We also found that proteomic information could be a useful marker to distinguish either between low and high grade tumors or between oligodendroglial- and astrocyte-derived ones. This demonstrates the applicability of FTIR coupled with ANNs to provide clinically relevant information.

Minor salivary gland mucinous adenocarcinoma of buccal mucosa - case report and review of the literature.

Mucinous adenocarcinoma (MAC) is commonly found in the gastrointestinal tract but head and neck localisations are very rare. This article presents the case of a 67-year-old patient suffering from a minor salivary gland MAC of the left buccal mucosa, who was treated in the Department of Cranio-Maxillofacial Surgery in Krakow due to multiple recurrences of the tumour. The results of immunohistochemical staining, the course of surgical treatment and follow-up, as well as a review of literature are also discussed.

Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing.

Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this trace element is involved in the integrity of the gastric mucosa. Compounds containing zinc, such as polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and ulcer healing remain unclear. We have determined the efficacy of zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at 3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after ulcer induction (day 0) and at day 3 but then it rose significantly at day 7 after ulcer induction. Treatment with zinc hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric luminal and mucosal levels of Zn(2+), significantly accelerated ulcer healing at day 7 upon ulcer induction. The GBF, which reached a significantly higher value at the ulcer margin than the ulcer bed, was significantly increased in rats treated with zinc hydroaspartate compared with vehicle-controls. The gastric acid output was significantly inhibited in GF rats with gastric ulcer at day 3 then restored at day 14 followed by a significant rise in the plasma gastrin levels. Treatment with zinc hydroaspartate significantly inhibited gastric secretion and also significantly raised the plasma gastrin level when compared to vehicle-control rats. We concluded that 1) trace micronutrients such as Zn(2+) could be successfully measured in the gastric juice and gastric mucosa during ulcer healing; 2) compounds chelating of Zn(2+) can exert a beneficial influence on the ulcer healing via Zn(2+) mediated increase in gastric microcirculation, antisecretory activity and gastrin release, which may enhance the cell proliferation and differentiation during ulcer healing, ultimately exerting a trophic action on the ulcerated gastric mucosa.

Pigmented creatine deposits in Amyotrophic Lateral Sclerosis central nervous system tissues identified by synchrotron Fourier Transform Infrared microspectroscopy and X-ray fluorescence spectromicroscopy.

Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinal cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases.

Two rare cases of pituitary metastases from breast and kidney cancers.

Pituitary metastases, though very uncommon, may cause endocrine and neurosurgical problems. The clinical manifestation of such metastases is highly variable. Most of the metastatic pituitary tumours are oligosymptomatic. We report two cases of metastatic pituitary lesions. The first patient, a 52-year old female, with metastatic breast cancer, developed symptomatic anterior pituitary insufficiency. The second patient, a 46-years old female presented with signs and symptoms of pituitary apoplexy and visual impairment due to metastasis from renal cancer. None of them was diagnosed with diabetes insipidus, the most common manifestation related to pituitary metastatic mass.

Implementation of X-ray fluorescence microscopy for investigation of elemental abnormalities in amyotrophic lateral sclerosis.

The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases.

Structural and energetic consequences of mutations in a solvated hydrophobic cavity.

The structural and energetic consequences of modifications to the hydrophobic cavity of interleukin 1-beta (IL-1beta) are described. Previous reports demonstrated that the entirely hydrophobic cavity of IL-1beta contains positionally disordered water. To gain a better understanding of the nature of this cavity and the water therein, a number of mutant proteins were constructed by site-directed mutagenesis, designed to result in altered hydrophobicity of the cavity. These mutations involve the replacement of specific phenylalanine residues, which circumscribe the cavity, with tyrosine, tryptophan, leucine and isoleucine. Using differential scanning calorimetry to determine the relative stabilities of the wild-type and mutant proteins, we found all of the mutants to be destabilizing. X-ray crystallography was used to identify the structural consequences of the mutations. No clear correlation between the hydrophobicities of the specific side-chains introduced and the resulting stabilities was found.

Analysis of the diffusion weighted MR microscopy data of excised spinal cord of a rat on the basis of the model of restricted diffusion.

Anisotropic diffusion in the excised rat spinal cord saturated with 0.9% saline was investigated using MR microimaging with b-values up to 8000 s/mm2 for different diffusion times. Non-exponential transversal diffusion decay found in white matter (WM) and gray matter (GM) was fitted with 2 components (the "fast" and the "slow"). Significantly smaller non-exponential dependence was found for the longitudinal diffusion in the WM. Obtained results corresponding to restricted diffusion in the range from approximately 2 to approximately 7 microm were correlated with axon diameter distribution in the WM obtained from transmission electron micrographs. It was concluded that observed diffusion anisotropy in the spinal cord might be entirely explained by presence of the slow transversal component, arising from the restricted diffusion. The strict analytical description of the diffusion decay in nervous tissue requires taking into account continuous distribution of the space-scale of the restricting barriers. The simplified two-component analysis may be applicable for visualization of the nervous tissue in clinical practice.

Dysembryoplastic neuroepithelial tumour (DNT). Is the mechanism of seizures related to glutamate? An immunohistochemical study.

Dysembryoplastic neuroepithelial tumour (DNT) is a rare low-grade, mixed neuronal and glial tumour, usually associated with pharmacologically intractable, complex partial or generalised seizures which date from childhood. The prognosis after surgery is favourable. We present a classic case of DNT occurring in an 18-year-old male, who presented simple partial seizures without signs of raised intracranial pressure. CT and MR demonstrated focal mass located in the right temporal lobe. Histologically there were found the features of a typical DNT architecture with mixed cellular composition. The response to surgery was excellent. The tumour has not recurred, and the control of seizures remained good. Immunostaining for glutamate receptor GluR-2 showed stronger immunopositivity in neurones dispersed within the tumour and especially in margins of lesion as compared with apparently normal cerebral cortex. The expression of both excitatoryamino acid transporterproteins EAAT1 and EAAT2 was weaker then in normal cortex and uneven. This perhaps may explain the mechanism of seizures (elevated glutaminergic stimulation), and may suggest the excitotoxic damage of neurones.

Immunohistochemical investigations of excitotoxicity in experimental spinal cord trauma.

The concept of "excitotoxicity" assumes that high concentration of glutamate (main excitatory neuromediator) acting through specific receptors leads to damage of cells due to an influx of calcium ions. Proteins called "excitatory amino acid transporters" (EAATs), present in astroglia, play important role in the removal of glutamate. We investigated the expression of GluR2 (glutamate receptor), EAAT1, and EAAT2 by immunohistochemistry in formalin-fixed, paraffin-embedded rat spinal cords, previously subjected to experimental mechanical trauma. In the injured spinal cords, an elevated immunoreactivity of GluR2 was noted even 10 min after trauma and was still observed 2 days after injury. Strong immunoreactivity was observed not only in many cells in gray matter but also in some cells in white matter (probably glial cells). In the injured spinal cords, we observed stronger (as compared with controls) expression of EAATs in the white matter, especially 6 hours after injury. The results support the role of excitotoxicity in mechanical trauma of spinal cord suggesting a possibility of long lasting elevated expression of glutamate receptor. It may help to understand and to explain beneficial action of "anti-glutamate" drugs, reported by other investigators.