microglia https://www.fiteyes.com/taxonomy/term/1343/all en Palmitoylethanolamide Stimulates Phagocytosis by Microglial Cells without Inducing an Inflammatory Reaction https://www.fiteyes.com/home/research/palmitoylethanolamide-stimulates-phagocytosis-by-microglial-cells-without-inducing-an <!-- THEME DEBUG --> <!-- CALL: theme('field') --> <!-- FILE NAME SUGGESTIONS: * field--body--section.tpl.php * field--section.tpl.php * field--body.tpl.php * field--text-with-summary.tpl.php x field--fences-div.tpl.php * field.tpl.php --> <!-- BEGIN OUTPUT from 'sites/all/modules/fences/templates/field--fences-div.tpl.php' --> <div class="field field-name-body field-type-text-with-summary field-label-hidden"> <p class="mb15">Summary: Palmitoylethanolamide (PEA), an endogenous lipid, increased phagocytosis of bacteria by microglial cells <i>in vitro</i> without a measurable proinflammatory effect. This allows the immune system to kill pathogens without harming nerve cells. Palmitoylethanolamide has been extensively tested clinically without observed severe side effects.<!--break--></p><p class="mb15">Palmitoylethanolamide (PEA) is a small endogenous lipid (molecular mass 299.5 g/mol) which is widely present in cells including microglia (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B55">Muccioli and Stella, 2008</a>), tissues and body fluids. It has analgesic, anticonvulsant, neuroprotective, antipyretic and anti-inflammatory properties. Its actions depend mainly on the peroxisome proliferator-activated receptor (PPAR)α, but it also is a ligand of the transient receptor potential vanilloid-1 (TRPV1) and the orphan G-protein coupled receptor GPR55 (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B18">De Petrocellis et al., 2001</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B47">LoVerme et al., 2005</a>, <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B48">2006</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B80">Ryberg et al., 2007</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B22">Esposito and Cuzzocrea, 2013</a>). In a murine Theiler’s virus model of chronic MS, treatment with PEA (5 mg/kg) between days 60 and 70 post-infection resulted in a strong improvement of motor deficits caused by a reduction of microglial activation observed in untreated mice (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B46">Loría et al., 2008</a>).</p><p class="mb0">In spite of its anti-inflammatory properties, 30 min pre-treatment with PEA stimulated phagocytosis of <i>S. pneumoniae</i> (EC<sub>50</sub> 5.9 nM) and <i>E. coli</i> (EC<sub>50</sub> 23 nM) by microglial cells <i>in vitro</i>. It was not toxic to microglial cells up to a concentration of 1000 nM. Unlike pre-stimulation with TLR and NOD2 agonists, the PEA-mediated increase of microglial bacterial uptake was not accompanied by a release of pro-inflammatory cyto-/chemokines [TNFα, IL-6, and CXCL1 (KC)], avoiding the risk of concomitant neuronal injury (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B70">Redlich et al., 2012</a>). Preliminary data suggest that PEA also decreases the susceptibility of the brain to intracerebral injection of bacteria (Sandra Redlich, unpublished data). From 1969 to 1979, PEA was tested under the brand name Impulsin<sup>R</sup> (SPOFA United Pharmaceutical Works, Prague, Czechoslovakia) in prophylactic and therapeutic clinical trials (five in adults, one in children): it reduced the incidence and severity of acute respiratory infections and influenza (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B36">Kahlich et al., 1979</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B38">Keppel Hesselink et al., 2013</a>). More than 3600 patients received PEA at daily doses from 600 to 1800 mg, and no severe adverse effects were reported (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B36">Kahlich et al., 1979</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B38">Keppel Hesselink et al., 2013</a>).These properties illustrate that PEA is a true immunomodulator and not an immunosuppressant and make PEA a promising agent to enhance the resistance of the brain against infection without carrying the risk of inducing neuronal injury (Figure <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#F6">6</a>). This effect may be of clinical value both in preventing bacterial CNS infections in high-risk groups and in reducing the invasion of pathogens into brain tissue in manifest meningeal infections.</p><p class="mb0"><img alt="" src="http://www.fiteyes.com/sites/www.fiteyes.com/files/_uploads_cck/field_images_inserted/fncel-08-00138-g006.jpg"></p><p class="mb0"><strong>FIGURE 6. Activation of microglia by Toll-like receptor (TLR) agonists and by palmitoylethanolamide (PEA).</strong> The activation by both ways leads to an increase of phagocytosis and intracellular killing of pathogens. Stimulation of one or several TLR or nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors causes the release of proinflammatory products from microglial cells causing neuronal injury in microglial-neuronal co-cultures and probably also in vivo. PEA also increases phagocytosis and intracellular killing of pathogens. To our knowledge, it does not release proinflammatory mediators. For this reason we hypothesize that it will not cause collateral neuronal injury. PEA probably acts via the peroxisome proliferator-activated receptor (PPAR)α, but also is a ligand of the transient receptor potential vanilloid-1 (TRPV1) and the orphan G-protein coupled receptor GPR55 (<a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B18">De Petrocellis et al., 2001</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B47">LoVerme et al., 2005</a>, <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B48">2006</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B80">Ryberg et al., 2007</a>; <a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full#B22">Esposito and Cuzzocrea, 2013</a>).</p><p class="mb0">Source:<br>Hypothesis &amp; Theory ARTICLE<br>Front. Cell. Neurosci., 22 May 2014 | doi: 10.3389/fncel.2014.00138<br>Strategies to increase the activity of microglia as efficient protectors of the brain against infections<br><a href="http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full">http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00138/full</a></p> </div> <!-- END OUTPUT from 'sites/all/modules/fences/templates/field--fences-div.tpl.php' --> <div class="field field-name-taxonomy-vocabulary-2 field-type-taxonomy-term-reference field-label-inline inline clearfix"><h3 class="field-label">Related Tags: </h3><ul class="links inline"><li class="taxonomy-term-reference-0"><a href="/tags/glaucoma">glaucoma</a></li><li class="taxonomy-term-reference-1"><a href="/tags/pea">PEA</a></li><li class="taxonomy-term-reference-2"><a href="/tags/peapure">PeaPure</a></li><li class="taxonomy-term-reference-3"><a href="/tags/palmitoylethanolamide">Palmitoylethanolamide</a></li><li class="taxonomy-term-reference-4"><a href="/tags/n-2-hydroxyethyl-palmitamide">N-(2-hydroxyethyl)-palmitamide</a></li><li class="taxonomy-term-reference-5"><a href="/tags/inflammation">inflammation</a></li><li class="taxonomy-term-reference-6"><a href="/tags/microglia">microglia</a></li><li class="taxonomy-term-reference-7"><a href="/tags/neuroprotection">neuroprotection</a></li></ul></div> Sat, 17 Jan 2015 05:43:59 +0000 dave 1657 at https://www.fiteyes.com Understanding dead vs dormant optic nerve cells https://www.fiteyes.com/blog/dave/understanding-dead-vs-dormant-optic-nerve-cells <div class="sharethis-buttons"><div class="sharethis-wrapper"><span st_url="https://www.fiteyes.com/blog/dave/understanding-dead-vs-dormant-optic-nerve-cells" st_title="Understanding%20dead%20vs%20dormant%20optic%20nerve%20cells" class="st_facebook_large" displayText="facebook"></span> <span st_url="https://www.fiteyes.com/blog/dave/understanding-dead-vs-dormant-optic-nerve-cells" st_title="Understanding%20dead%20vs%20dormant%20optic%20nerve%20cells" class="st_twitter_large" displayText="twitter" st_via="" st_username=""></span> <span st_url="https://www.fiteyes.com/blog/dave/understanding-dead-vs-dormant-optic-nerve-cells" st_title="Understanding%20dead%20vs%20dormant%20optic%20nerve%20cells" class="st_sharethis_large" displayText="sharethis" st_via="" st_username=""></span> </div></div> <div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"><p>A FitEyes member sent some comments and questions today regarding what happens to dead or non-functional optic nerve cells. I have replied inline below so you can read his comments and my responses.</p> <blockquote><div>I am impressed with the enormous amount of knowledge some of you have about glaucoma.</div> </blockquote> <div> </div> <div>Thanks for saying that. I too am impressed by the wealth of knowledge in our community!<br /> </div> <blockquote><div dir="ltr"> <div>I was diagnosed with glaucoma two years ago and as all of you am looking for ways to get better.</div> </div> </blockquote> <div> </div> <div>I believe we can improve. It is my belief that the optic nerve can regenerate.<br /> </div> <blockquote><div dir="ltr"> <div>Q. Can anyone tell me what happens to dead optic nerve cells (ONC)? Does the body flush them away or do they remain in their shriveled state?</div> </div> </blockquote> <div> </div> <div>In glaucoma apoptosis (as opposed to necrosis) is the main pathway to retinal ganglion cell death. Apoptosis is a natural type of self-induced destruction. (It is called programmed cell death, although I personally think that term is misleading.) It is contrasted with externally induced tramatic destruction (necrosis).<br /><br />However, <b>apoptosis does occur in response to the cell's environment </b>(as noted below). So if you want to call it <i>programmed cell death</i>, note that information from the cell's environment is the input into this program. Something triggers the program to run. It is a response to the milieu and I see it in a holistic way (which is not always how it is explained in the textbooks).<br /><br />In the eye there is rapid <b>phagocytosis of the apoptotic debris</b>. This means that immune cells (e.g. glial cells) engulf the apoptotic debris. This is a type of clean up process. It helps prevent auto-immune responses and other unwanted responses. However, some experts feel that, in glaucoma, the phagocytosis often extends to nearby healthy retinal ganglion cells, thus spreading the damage beyond what the ideal natural process would represent. This is all my own understanding. I trust that any experts reading the above will offer any needed corrections.<br /><br /><br /><div style="margin-left: 40px;">From <a href="http://dx.doi.org/10.5772/54294"><i>Neuroprotection in Glaucoma</i></a>: Mechanisms believed to cause stress to retinal ganglion cells and to initiate the apoptotic cascade include:</div> <ul style="margin-left: 40px;"><li>biomechanical stress [52, 53],</li> <li>excitotoxicity [54-57],</li> <li>tissue hypoxia (insufficient oxygen) [58, 59],</li> <li>altered nutritional blood supply [60, 61],</li> <li>mitochondrial dysfunction [62-65],</li> <li>Müller glial cell activation (glial hyperactivation) [66],</li> <li>protein misfolding [67-69],</li> <li>oxidative stress [70, 71],</li> <li>dysfunctional autoimmunity [72],</li> <li>neurotrophin deprivation [73, 74],</li> <li>inflammation [75, 76]</li> <li>(see references below)</li> </ul></div> <blockquote><div dir="ltr"> <div>Q. There also must be millions of  stunted, dormant," hibernating" ONCs, for otherwise how can microcurrent bring them partly back to life?</div> </div> </blockquote> <div> </div> <div>I think the above facts give a slightly different perspective. However, there do appear to be some number of retinal ganglion cells that can regain function.</div> <div> </div> <blockquote><div dir="ltr"> <div>Q. This procedure is available in Germany but is expensive and seems to last less than a year.</div> </div> </blockquote> <div> </div> <div>It's too new to say much about how long it lasts or what its true potential is. It is also too early to say if it is the ideal way to revive the non-functional cells. My own belief is that meditation is a superior (and safer) way to achieve this result.<br /> </div> <blockquote><div dir="ltr"> <div>Q. I would like to believe in resurrection for the only alternative is stem cell therapy which is probably a dozen years away.</div> </div> </blockquote> <div> </div> <div>No, there are many other possible alternatives. I don't think it is healthy for us patients to close our minds to all the alternatives. After all, given that stem cells are a natural process, why does it require medical intervention for us to take advantage of this process? I think natural methods such as meditation can trigger the natural process of optic nerve regeneration, although science may not yet know that...</div> </div></div></div><div class="field field-name-taxonomy-vocabulary-2 field-type-taxonomy-term-reference field-label-inline inline clearfix"><h3 class="field-label">Filed Under (tags): </h3><ul class="links inline"><li class="taxonomy-term-reference-0"><a href="/tags/glaucoma">glaucoma</a></li><li class="taxonomy-term-reference-1"><a href="/tags/optic-nerve">optic nerve</a></li><li class="taxonomy-term-reference-2"><a href="/tags/retinal-ganglion-cells">retinal ganglion cells</a></li><li class="taxonomy-term-reference-3"><a href="/tags/apoptosis">apoptosis</a></li><li class="taxonomy-term-reference-4"><a href="/tags/phagocytosis">phagocytosis</a></li><li class="taxonomy-term-reference-5"><a href="/tags/glial-cells">glial cells</a></li><li class="taxonomy-term-reference-6"><a href="/tags/microglia">microglia</a></li></ul></div> Sun, 30 Nov 2014 19:31:50 +0000 dave 1649 at https://www.fiteyes.com