Dynamic changes in the expression pattern of ecto-5'-nucleotidase in the rat model of cortical stab injury.

Traumatic injury induces massive release of ATP in the extracellular space, where it influences numerous aspects of neuronal, astrocytic, and microglial responses to injury by activating P2X and P2Y receptors. The extracellular ATP actions are controlled by the ectonucleotidase enzyme pathway, which hydrolyses ATP to adenosine at all neuronal and nonneuronal cell types. Adenosine activates its P1 receptors, which have important neuroprotective roles.

Ribavirin administration alters ectonucleotidase activities in experimental autoimmune encephalomyelitis.

The role of extracellular purines and purinoreceptors in the pathophysiology of different neurological disorders is the focus of rapidly expanding area of research. Ectonucleotidases are the enzymes with multiple roles in extracellular nucleotides metabolism and regulation of nucleotidebased intercellular signaling. The aim of present study was to investigate the changes in the ATP, ADP and AMP hydrolyzing activities after ribavirin treatment in spinal cord during experimental autoimmune encephalomyelitis (EAE).

Regional changes in ectonucleotidase activity after cortical stab injury in rat.

During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering local cellular and biochemical responses to injury. Different models of brain injury reveal that the local increase in adenine nucleotides levels is followed by a compensatory up-regulation of ectonucleotidase enzymes that catalyze sequential hydrolysis of ATP to ADP, AMP and adenosine. However, recent studies imply that changes in adenine nucleotides release may also occur in the areas distant from the site of direct damage.

Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production.

To determine the mechanism underlying ribavirin induced amelioration of experimental autoimmune encephalomyelitis (EAE), cytokine profiles were evaluated in draining lymph node (DLN) cell culture supernatants and spinal cord obtained from EAE and/or ribavirin-treated EAE Dark Agouti rats. Administration of ribavirin to EAE rats markedly affected the production of pro-inflammatory cytokines IFN-gamma, IL-1beta and TNF-alpha in DLN and spinal cord, thus shifting the balance towards the anti-inflammatory cytokines IL-10 and TGF-beta. These findings suggest that ribavirin attenuates EAE by limiting cytokine-mediated immunoinflammatory events leading to CNS destruction.

Therapeutic effects of combined treatment with ribavirin and tiazofurin on experimental autoimmune encephalomyelitis development: clinical and histopathological evaluation.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and the helpful tool in preclinical testing of various substances considered for treatment of this human CNS disease. Ribavirin (R) and tiazofurin (T) are purine nucleoside analogues, with the broad spectrum of anti-viral, anti-tumoral and anti-inflammatory properties. We proposed that combined treatment with RT, administrated during the effector phase of EAE, would attenuate disease severity, both clinically and pathologically.

Early temporal changes in ecto-nucleotidase activity after cortical stab injury in rat.

During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering multiple cellular responses to injury. Here, we evaluated changes in extracellular ATP, ADP and AMP hydrolysis at different times (0-24 hours) after unilateral cortical stab injury (CSI) in adult rats. Results demonstrated that 24 hours following CSI, ATP and ADP hydrolyzing activities were not significantly altered in injured cortex.

Immunohistological determination of ecto-nucleoside triphosphate diphosphohydrolase1 (NTPDase1) and 5'-nucleotidase in rat hippocampus reveals overlapping distribution.

Distribution of two enzymes involved in the ectonucleotidase enzyme chain, ecto-nucleoside triphosphate diphosphohydrolase1 (NTPDase1) and ecto-5'-nucleotidase, was assessed by immunohistochemistry in the rat hippocampus. Obtained results have shown co-expression of the enzymes in the hippocampal region, as well as wide and strikingly similar cellular distribution. Both enzymes were expressed at the surface of pyramidal neurons in the CA1 and CA2 sections, while cells in the CA3 section were faintly stained.

Immunolocalization of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in the rat forebrain.

Immunohistochemical study was performed to determine distribution of ecto-nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) in adult rat forebrain. The study revealed widespread distribution of NPP1 in rat forebrain, yet with regional differences in the expression pattern and abundance. Strong NPP1 immunoreaction was detected in pyramidal cell layer of cerebral cortex and hippocampus, and in the midline regions of hypothalamus and thalamus.

Up-regulation of ectonucleotidase activity after cortical stab injury in rats.

The objective of this study was to examine the changes in the activity and expression of ectonucleotidase enzymes in the model of unilateral cortical stab injury (CSI) in rat. The activities of ecto-nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1) and ecto 5'-nucleotidase were assessed by measuring the levels of ATP, ADP and AMP hydrolysis in the crude membrane preparations obtained from injured left cortex, right cortex, left and right caudate nucleus, whole hippocampus and cerebellum. Significant increase in NTPDase and ecto 5'-nucleotidase activities was observed in the injured cortex following CSI, whereas in other brain areas only an increase in ecto 5'-nucleotidase activity was seen.

Combination of nucleoside analogues tiazofurin and ribavirin downregulates experimental autoimmune encephalomyelitis.

The effect of combined treatment with ribavirin and tiazofurin on the development of experimental autoimmune encephalomyelitis, the best characterized animal model for human autoimmune disease multiple sclerosis, was investigated. The disease was induced in highly susceptible Dark Agouti rats with spinal cord homogenate in complete Freund's adjuvant. Although ribavirin or tiazofurin alone reduced the clinical and histopathological signs of experimental autoimmune encephalomyelitis, the combination of drugs achieved the same effect with significantly lower doses.

Downregulation of glial scarring after brain injury: the effect of purine nucleoside analogue ribavirin.

The weak regenerative capacity of self-repair after injury to the adult brain is caused by the formation of glial scar due to reactive astrogliosis. In the present study the beginning of reactive astrogliosis in the adult, as shown immunocytochemically by upregulation of glial fibrillary acidic protein (GFAP) and vimentin, was seen two days after the left sensorimotor cortex lesion, being maximal during the first two weeks and declining by 30 days after the lesion. This was accompanied by intensive glial scarring.