Anterior chamber associated immune deviation to cytosolic neural antigens avoids self-reactivity after optic nerve injury and polarizes the retinal environment to an anti-inflammatory profile.

It has been hypothesized that anterior chamber-associated immune deviation (ACAID) to neural antigens induced prior to central nervous system injury can inhibit self-reactivity and lessen secondary degeneration. This work evaluated the effect of ACAID induced to three neural tissue-derived extracts (whole extract, cytosolic extract, CE; or organelle-membrane extract) prior to optic nerve injury on retinal ganglion cell (RGC) survival. The results show that only ACAID to the CE increased RGC survival at 7 and14 days post-injury (dpi). This effect was achieved by retinal polarization towards an anti-inflammatory profile, driven by regulatory T cells and M2-type macrophages at 7 dpi.

ACAID as a potential therapeutic approach to modulate inflammation in neurodegenerative diseases.

The progressive loss of neurons and inflammation characterizes neurodegenerative diseases. Although the etiology, progression and outcome of different neurodegenerative diseases are varied, they share chronic inflammation maintained largely by central nervous system (CNS)-derived antigens recognized by T cells. Inflammation can be beneficial by recruiting immune cells to kill pathogens or to clear cell debris resulting from the primary insult. However, chronic inflammation exacerbates and perpetuates tissue damage. An increasing number of therapies that attempt to modulate neuroinflammation have been developed. However, so far none has succeeded in decreasing the secondary damage associated with chronic inflammation. A potential strategy to modulate the immune system is related to the induction of tolerance to CNS antigens. In this line, it is our hypothesis that this could be accomplished by using anterior chamber associated immune deviation (ACAID) as a strategy. Thus, we review current knowledge regarding some neurodegenerative diseases and the associated immune response that causes inflammation. In addition, we discuss further our hypothesis of the possible usefulness of ACAID as a therapeutic strategy to ameliorate damage to the CNS.

Pentoxifylline downregulates alpha (I) collagen expression by the inhibition of Ikappabalpha degradation in liver stellate cells.

Overproduction of collagen (I) by activated hepatic stellate cells is a critical step in the development of liver fibrosis. It has been established that these cells express interleukin (IL)-6 and respond to this cytokine with an increase in alpha(I) collagen. Pentoxifylline, a methylxanthine derivate, has been reported to have antifibrotic properties, but the mechanism responsible for this effect is unknown. The aim of this study was to determine the effect of pentoxifylline on acetaldehyde-induced collagen production in a rat hepatic stellate cell line (CFSC-2G cells). Cells were treated with 100 microM acetaldehyde and 200 microM pentoxifyline for 3 h. IL-6 and alpha(I) collagen messenger RNA (mRNA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) assay. NFkappaB activation was determined by electrophoretic mobility shift assay. To corroborate NFkappaB participation in pentoxifylline effect, cells were pretreated with 10 microM TPCK, a NFkappaB inhibitor. IkappaBalpha was determined by Western blot. IL-6 expression decreased significantly in acetaldehyde-pentoxifylline-treated cells. Acetaldehyde-treated cells pretreated with an anti-IL-6 monoclonal antibody did not show any increase in alpha (I) collagen expression. Acetaldehyde-treated cells increased 1.48 times NFkappaB activation, whereas acetaldehyde-pentoxifylline-treated cells decreased NFkappaB activation to control values. TPCK pretreated acetaldehyde cells did not present NFkappaB activation. To corroborate NFkappaB participation in pentoxifylline effect, IkappaBalpha was determined. IkappaBalpha protein level decreased 50% in acetaldehyde-treated cells, while acetaldehyde-pentoxifylline-treated cells showed IkappaBalpha control cells value. The data suggest that acetaldehyde induced alpha(I) collagen and IL-6 expression via NFkappaB activation. Pentoxifylline prevents acetaldehyde-induced alpha(I) collagen and IL-6 expression by a mechanism dependent on IkappaBalpha degradation, which in turn blocks NFkappaB activation.

c-Fos expression related to sexual satiety in the male rat forebrain.

The long term inhibition of masculine sexual behavior after repeated ejaculations is known as sexual satiety. To investigate the brain areas that may regulate sexual satiety, c-Fos expression was studied in different groups of sexually experienced male rats: controls not allowed to copulate, males allowed two or four ejaculations and animals allowed to reach sexual satiety. Interestingly, males that ejaculated two or four times had similar c-Fos densities in all the evaluated brain regions, except for the suprachiasmatic nucleus. Similarly, sexually satiated males had analogous c-Fos densities in all the evaluated brain areas independently of the number of ejaculations required to reach satiety. Sexual activity (evidenced in males that ejaculated two or four times) increased c-Fos levels in the anteromedial bed nucleus of the stria terminalis, claustrum, entorhinal cortex, medial preoptic area, nucleus accumbens core, suprachiasmatic nucleus and supraoptic nucleus; however, sexual satiety did not modify c-Fos expression in these regions. Sexually satiated males had increased c-Fos densities in the ventrolateral septum and the anterodorsal and posteroventral medial amygdala, compared with animals allowed to copulate but that did not reach sexual satiety, and decreased c-Fos density in the piriform cortex. These results suggest that the network that underlies sexual satiety is different from that which regulates copulation.