Mahalia S Desruisseaux, Dumitru A Iacobas, Sanda Iacobas, Shankar Mukherjee, Louis M Weiss, Herbert B Tanowitz, David C Spray
{"title":"Alterations in the Brain Transcriptome in <i>Plasmodium Berghei</i> ANKA Infected Mice.","authors":"Mahalia S Desruisseaux, Dumitru A Iacobas, Sanda Iacobas, Shankar Mukherjee, Louis M Weiss, Herbert B Tanowitz, David C Spray","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have used cDNA microarrays to compare gene expression profiles in brains from normal mice to those infected with the ANKA strain of <i>Plasmodium berghei</i>, a model of cerebral malaria. For each of three brains in each group, we computed ratios of all quantifiable genes with a composite reference sample and then computed ratios of gene expression in infected brains compared to untreated controls. Of the almost 12,000 unigenes adequately quantified in all arrays, approximately 3% were significantly downregulated (<i>P <</i> 0.05, ≥ 50% fold change) and about 7% were upregulated. Upon inspection of the lists of regulated genes, we identified a high number encoding proteins of importance to normal brain function or associated with neuropathology, including genes that encode for synaptic proteins or genes involved in cerebellar function as well as genes important in certain neurological diseases such as Alzheimer's disease or autism. These results emphasize the important impact of malarial infection on gene expression in the brain and provide potential biomarkers that may provide novel therapeutic targets to ameliorate the neurological sequelae of this infection.</p>","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587055/pdf/nihms435859.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Desruisseaux, D. Iacobas, S. Iacobaş, Shankar Mukherjee, L. Weiss, H. Tanowitz, D. Spray
{"title":"Alterations in the Brain Transcriptome in Plasmodium Berghei ANKA Infected Mice.","authors":"M. Desruisseaux, D. Iacobas, S. Iacobaş, Shankar Mukherjee, L. Weiss, H. Tanowitz, D. Spray","doi":"10.4303/JNP/N100803","DOIUrl":"https://doi.org/10.4303/JNP/N100803","url":null,"abstract":"We have used cDNA microarrays to compare gene expression profiles in brains from normal mice to those infected with the ANKA strain of Plasmodium berghei, a model of cerebral malaria. For each of three brains in each group, we computed ratios of all quantifiable genes with a composite reference sample and then computed ratios of gene expression in infected brains compared to untreated controls. Of the almost 12,000 unigenes adequately quantified in all arrays, approximately 3% were significantly downregulated (P < 0.05, ≥ 50% fold change) and about 7% were upregulated. Upon inspection of the lists of regulated genes, we identified a high number encoding proteins of importance to normal brain function or associated with neuropathology, including genes that encode for synaptic proteins or genes involved in cerebellar function as well as genes important in certain neurological diseases such as Alzheimer's disease or autism. These results emphasize the important impact of malarial infection on gene expression in the brain and provide potential biomarkers that may provide novel therapeutic targets to ameliorate the neurological sequelae of this infection.","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71099679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trypanosoma cruzi-Derived Neurotrophic Factor: Role in Neural Repair and Neuroprotection.","authors":"Marina V Chuenkova, Mercio Pereiraperrin","doi":"10.4303/jnp/N100507","DOIUrl":"https://doi.org/10.4303/jnp/N100507","url":null,"abstract":"<p><p>Some patients infected with the parasite Try-panosoma cruzi develop chronic Chagas' disease, while others remain asymptomatic for life. Although pathological mechanisms that govern disease progression remain unclear, the balance between degeneration and regeneration in the peripheral nervous system seems to contribute to the different clinical outcomes. This review focuses on certain new aspects of host-parasite interactions related to regeneration in the host nervous system induced by the trans-sialidase of T. cruzi, also known as a parasite-derived neurotrophic factor (PDNF). PDNF plays multiple roles in T. cruzi infection, ranging from immunosuppression to functional mimicry of mammalian neurotrophic factors and inhibition of apoptosis. PDNF affinity to neurotrophin Trk receptors provide sustained activation of cellular survival mechanisms resulting in neuroprotection and neuronal repair, resistance to cytotoxic insults and enhancement of neuritogenesis. Such unique PDNF-elicited regenerative responses likely prolong parasite persistence in infected tissues while reducing neuropathology in Chagas' disease.</p>","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":" ","pages":"55-60"},"PeriodicalIF":0.0,"publicationDate":"2010-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092389/pdf/nihms254024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29883726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jason E Perlman, Kevin R Kazacos, Gavin H Imperato, Rajen U Desai, Susan K Schulman, Jon Edwards, Lucy R Pontrelli, Fabiana S Machado, Herbert B Tanowitz, Norman A Saffra
{"title":"<i>Baylisascaris Procyonis</i> Neural Larva Migrans in an Infant in New York City.","authors":"Jason E Perlman, Kevin R Kazacos, Gavin H Imperato, Rajen U Desai, Susan K Schulman, Jon Edwards, Lucy R Pontrelli, Fabiana S Machado, Herbert B Tanowitz, Norman A Saffra","doi":"10.4303/jnp/N100502","DOIUrl":"https://doi.org/10.4303/jnp/N100502","url":null,"abstract":"<p><p>Neural larva migrans (NLM) with eosinophilic meningoencephalitis secondary to raccoon roundworm (<i>Baylisascaris procyonis</i>) infection has been reported in rural and suburban areas of North America and Europe with extant raccoon populations. Most cases have occurred in infants less than two years of age exposed to areas of raccoon fecal contamination. Here, we present a case of <i>Baylisascaris</i>-induced NLM from the densely populated borough of Brooklyn in New York City and alert urban pediatricians to consider this cause of clinical neurologic disease even in areas not typically thought to be associated with endemic risk factors. Infected raccoons also occur in urban settings, and urban children may be exposed to environmental areas or materials contaminated with their feces and the parasite's eggs.</p>","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205936/pdf/nihms444300.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32773340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increasing Intracerebral Infections Caused by Free-Living Amebae in the United States and Worldwide","authors":"J. Diaz","doi":"10.4303/JNP/N100801","DOIUrl":"https://doi.org/10.4303/JNP/N100801","url":null,"abstract":"Free-living amebae of the genera Acanthamoeba, Balamuthia, Naegleria, and Sappinia are rare causes of infectious diseases in humans with the exception of Acanthamoeba keratitis (AK) which is reported in millions of soft contact lens wearers worldwide each year. Unlike several Acanthamoeba species, only one species of Naegleria, N. fowleri, is known to infect humans by causing an acute, fulminant, usually lethal, central nervous system (CNS) infection, known as primary amebic meningoencephalitis (PAM). Balamuthia mandrillaris, another opportunistic, free-living ameba, is, like Acanthamoeba spp., capable of causing skin lesions and granulomatous amebic encephalitis (GAE) in individuals with compromised or competent immune systems, who inhale infective cysts or develop indolent, granulomatous skin lesions in soil-contaminated wounds. Lastly, Sappinia pedata, a recently identified free-living ameba that lives in soil and animal and reptile feces, has caused a single case of nongranulomatous amebic encephalitis in an immunocompetent Texas farmer. CNS infections caused by these ubiquitous organisms remain rare, but are, nevertheless, increasing today in the US and worldwide due to a combination of environmental and host susceptibility factors. The purpose of this review will be to describe the current epidemiology, pathophysiology, clinical manifestations, diagnosis, management, and prevention of free-living amebic infections of the CNS.","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71098960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Validity of Modelling Cerebral Malaria in Mice: Argument and Counter Argument","authors":"A. Taylor-Robinson","doi":"10.4303/JNP/N100601","DOIUrl":"https://doi.org/10.4303/JNP/N100601","url":null,"abstract":"The clinical manifestations of Plasmodium falciparum infection of humans that are collectively recognised as cerebral malaria produce profound changes in mental status and induce coma. The histopathological hallmark of this encephalopathy is the sequestration of cerebral capillaries and venules with both infected and uninfected erythrocytes. The underlying cause of cerebral malaria is the subject of vigorous debate. A major reason for this is that human brain tissue is only available post mortem. In order to dissect the pathology of this acute disease, therefore, a number of models using murine malarias have been developed. While these have undoubtedly proved useful in helping to identify immunological mechanisms involved, recognition of the differences between the pathological processes during cerebral malaria in mice and man has led to some researchers questioning the validity of extrapolating findings from mouse models to the human condition with a view to informing therapeutic interventions. In turn, this has provoked lively debate within the malaria research community. This commentary sets out our current understanding of cerebral disease in humans and evaluates what meaningful contribution the study of mouse models has made to this knowledge.","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":"45-49"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71098899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. A. Silva, G. Pereira, A. S. Souza, Rafael Rodrigues Silva, M. Rocha, J. Lannes-Vieira
{"title":"Trypanosoma cruzi-Induced Central Nervous System Alterations: From the Entry of Inflammatory Cells to Potential Cognitive and Psychiatric Abnormalities","authors":"A. A. Silva, G. Pereira, A. S. Souza, Rafael Rodrigues Silva, M. Rocha, J. Lannes-Vieira","doi":"10.4303/JNP/N100901","DOIUrl":"https://doi.org/10.4303/JNP/N100901","url":null,"abstract":"Trypanosoma cruzi, a protozoan parasite and the causative agent of Chagas disease, is capable of inducing meningoencephalitis. Independent of the progression from acute to chronic myocarditis observed in immunocompetent T. cruzi-infected patients, inflammation of the central ner- vous system (CNS) self-resolves during acute infection. In contrast, in chronically infected immunocompromised Cha- gas disease patients, the CNS is a major site of reactivation, which can lead to severe and frequently fatal meningoen- cephalitis. More than one hundred years after the discovery of Chagas disease, many questions concerning the molecu- lar mechanisms involved in the induction and resolution of T. cruzi-provoked meningoencephalitis remain unanswered. The study of murine models that reproduce crucial aspects of T. cruzi-elicited CNS inflammation has not only shed light on some of these questions, but it has also raised additional ones. Here, we discuss our results in the context of the cur- rent literature, questioning the involvement of CNS alter- ations caused by the inflammation and parasite in the behav- ioral abnormalities observed during T. cruzi infection.","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71099362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. García, P. Dorny, Yesenia Castillo, E. Pretell, Silvia Rodriguez, L. Mija, Armando E. Gonzalez, R. Gilman, V. Tsang, J. Brandt
{"title":"Circulating Antigen Levels Follow Post-Treatment Evolution of Subarachnoid Neurocysticercosis","authors":"H. García, P. Dorny, Yesenia Castillo, E. Pretell, Silvia Rodriguez, L. Mija, Armando E. Gonzalez, R. Gilman, V. Tsang, J. Brandt","doi":"10.4303/JNP/N100804","DOIUrl":"https://doi.org/10.4303/JNP/N100804","url":null,"abstract":"Subarachnoid neurocysticercosis carries poor prognosis and high mortality. Besides neuroimaging, there are no available monitoring tools. We examined antigen levels in sequential serum samples of a patient who required four courses of antiparasitic treatment. Antigen levels decreased in parallel to parasite resolution. Antigen detection may contribute to monitoring treatment of subarachnoid neurocysticercosis.","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":"1 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71099353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host Cell Preference of Toxoplasma gondii Cysts in Murine Brain: A Confocal Study.","authors":"T C Melzer, H J Cranston, L M Weiss, S K Halonen","doi":"10.4303/jnp/N100505","DOIUrl":"https://doi.org/10.4303/jnp/N100505","url":null,"abstract":"<p><p>Toxoplasma gondii is a protozoan parasite that is widely prevalent in humans and typically results in a chronic infection characterized by cysts located predominantly in the central nervous system. In immunosuppressed hosts, such as patients with HIV infection, the infection can be reactivated from the cysts in the brain resulting in a severe and potentially fatal encephalitis. Studies suggest that the chronic infection may also have neuropathological and behavioral effects in immune competent hosts. An improved understanding of tissue cyst behavior is of importance for understanding both the reactivation as well as the neurophysiological consequences of chronic infection. In vivo studies have identified neurons as host cells for cysts but in vitro studies have found that astrocytes can also foster development of the cysts. In this study we have addressed the question of which neural cell tissue cysts of T. gondii reside during chronic infection using a mouse model. Mice were infected with Me49 Strain T. gondii and the intracellular localization of the cysts analyzed during the development and establishment of a chronic infection at 1, 2, and 6 months post infection. Brains were fixed, cryosectioned, and stained with FITC-Dolichos biflorans to identify the Toxoplasma cysts and they were labeled with cell specific antibodies to neurons or astrocytes and then analyzed using confocal fluorescence microscopy. Cysts were found to occur almost exclusively in neurons throughout chronic infection. No cysts were identified in astrocytes, using the astrocyte marker, GFAP. Astrocyte interactions with neuronal-cysts, however, were frequently observed.</p>","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4303/jnp/N100505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30204420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norman A Saffra, Jason E Perlman, Rajen U Desai, Kevin R Kazacos, Christina M Coyle, Fabiana S Machado, Sanjay R Kedhar, Michael Engelbert, Herbert B Tanowitz
{"title":"Baylisascaris Procyonis Induced Diffuse Unilateral Subacute Neuroretinitis in New York City.","authors":"Norman A Saffra, Jason E Perlman, Rajen U Desai, Kevin R Kazacos, Christina M Coyle, Fabiana S Machado, Sanjay R Kedhar, Michael Engelbert, Herbert B Tanowitz","doi":"10.4303/jnp/N100401","DOIUrl":"https://doi.org/10.4303/jnp/N100401","url":null,"abstract":"<p><p>Diffuse unilateral subacute neuroretinitis (DUSN) secondary to raccoon roundworm (Baylisascaris procyonis) infection has been reported in rural and suburban areas of North America and Europe with extant raccoon populations. Here, we present a case of Baylisascaris-induced DUSN from the densely populated borough of Brooklyn in New York City and alert urban ophthalmologists to consider this etiology even in areas not typically thought to be associated with endemic risk factors. Infected raccoons also occur in urban settings, and urban patients may be exposed in surrounding areas. Most patients with Baylisascaris ocular larva migrans-DUSN will not have concomitant neurologic disease; this fact and larval neurotropism are both misconceptions regarding this infection.</p>","PeriodicalId":73863,"journal":{"name":"Journal of neuroparasitology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278166/pdf/nihms347470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30462376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}