{"id":17103,"date":"2014-09-11T14:47:55","date_gmt":"2014-09-11T18:47:55","guid":{"rendered":"http:\/\/therapytoronto.ca\/news\/?p=17103"},"modified":"2014-09-15T04:12:20","modified_gmt":"2014-09-15T08:12:20","slug":"why-hiv-patients-develop-dementia","status":"publish","type":"post","link":"https:\/\/therapytoronto.ca\/news\/2014\/09\/why-hiv-patients-develop-dementia\/","title":{"rendered":"Why HIV patients develop dementia"},"content":{"rendered":"<p>From the Ruhr-University Bochum media release:<\/p>\n<blockquote><p><a href=\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2013\/07\/blood-samples-fridge.jpg\"><img loading=\"lazy\" class=\"alignright size-full wp-image-15092\" alt=\"blood samples fridge\" src=\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2013\/07\/blood-samples-fridge.jpg\" width=\"290\" height=\"177\" \/><\/a>Since the introduction of the combination anti-retroviral therapy (cART) in the mid-90s, <strong>the life expectancy of HIV patients has significantly improved<\/strong>.<\/p>\n<p>As a result, long-term complications are becoming more relevant: <strong>almost every second HIV patient is affected by neurocognitive disorders, which can lead to dementia<\/strong>. It has not as yet been fully understood how these disorders occur. Researchers from Bochum have now successfully demonstrated that infected cells activate specific immune cells in a patient&#8217;s brain, which subsequently display harmful behaviour and lead to the destruction of neurons. These findings may help develop biomarkers to identify risk patients and to make a therapeutic strategy possible in the long term. The study was published in the trade journal <em>Experimental Neurology<\/em>.<\/p>\n<h3>Immune Cells in the Brain Under Suspicion<\/h3>\n<p>&#8220;HIV-associated neurocognitive disorders&#8221; (HAND) include disorders of the cognitive functions, motor capacities as well as behavioural changes. How exactly HAND occur has not, as yet, been fully understood. &#8220;Scientists assume that HIV is harmful to cells directly and that is also triggers indirect mechanisms that lead to nerve cell damage,&#8221; explains Dr Simon Faissner (RUB clinic for neurology, St. Josef-Hospital). The <strong>researchers strongly suspect that, once activated in the brain and the spinal cord, immune cells keep up a chronic inflammation level which then results in the destruction of nerve cells<\/strong>. An immune activation in peripheral tissue as well as therapeutic consequences may likewise contribute to nerve cell damage in the brain.<\/p>\n<h3>First Steps of HIV Infection are Sufficient<\/h3>\n<p>The HI virus overcomes the blood-brain barrier hitchhiking on infected immune cells, the monocytes and probably the T cells. <strong>The researchers from Bochum tested the hypothesis that HIV-infected monocytes activate specific immune cells in the brain, the so-called microglial cells<\/strong>. These cells, in turn, respond by releasing harmful substances, such as reactive oxygen metabolites and inflammatory signalling molecules, i.e. cytokines.<\/p>\n<p>To test this hypothesis, the researchers developed a cell culture system in which they initially examined the effect of HIV-infected monocytes on microglial cells. The researchers simulated the individual steps of HIV infection and measured the volume of the cytokines released at each stage. <strong>Thus, they were able to demonstrate that releasing the viral RNA in the monocytes was a sufficient trigger for maximal microglial activation<\/strong>. Subsequent infection phases &#8212; reverse transcription into DNA and the resulting formation of HIV proteins &#8212; did not augment activation any further.<\/p>\n<h3>Released Substances Result in Neuronal Cell Death<\/h3>\n<p>In the second step, they analysed nerve cells from rat brains to determine if the substances released by the microglial cells could lead to cell death. <strong>Compared with the control group, the number of cell deaths was indeed twice as high<\/strong>. Studies of liquor cerebrospinalis received from HIV-infected patients have shown a positive correlation with marker of neuronal degeneration in patients who did not as yet present any neurocognitive disorders.<\/p>\n<h3>Detailed Understanding Necessary for Therapeutic Strategies<\/h3>\n<p>&#8220;Thanks to our research, we have gained a better understanding of the mechanisms of HIV-associated neurodegeneration,&#8221; concludes Prof Dr Andrew Chan. &#8220;These results are likely to contribute to HAND biomarkers becoming established. <strong>In the long term, these data will be used to develop therapeutic strategies aiming at retarding HAND progression in HIV-infected patients.<\/strong>&#8221; Starting points may include activation of microglial cells &#8212; a method that is applied in other autoimmune diseases of the central nervous system, for example in multiple sclerosis.<\/p><\/blockquote>\n<!-- AddThis Advanced Settings generic via filter on the_content --><!-- AddThis Share Buttons generic via filter on the_content -->","protected":false},"excerpt":{"rendered":"<p>From the Ruhr-University Bochum media release: Since the introduction of the combination anti-retroviral therapy (cART) in the mid-90s, the life expectancy of HIV patients has significantly improved. As a result,&#8230; <a class=\"read-more-link\" href=\"https:\/\/therapytoronto.ca\/news\/2014\/09\/why-hiv-patients-develop-dementia\/\">Read more &raquo;<\/a><!-- AddThis Advanced Settings generic via filter on get_the_excerpt --><!-- AddThis Share Buttons generic via filter on get_the_excerpt --><\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[357,10,358,4],"tags":[],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/17103"}],"collection":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=17103"}],"version-history":[{"count":1,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/17103\/revisions"}],"predecessor-version":[{"id":17108,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/17103\/revisions\/17108"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=17103"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=17103"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=17103"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}