Involvement of ectonucleotidases and purinergic receptor expression during acute Chagas disease in the cortex of mice treated with resveratrol and benznidazole.

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. CD affects people worldwide, primarily in tropical areas. The central nervous system (CNS) is an essential site for T. cruzi persistence during infection. The protozoan may pass through the blood-brain barrier and may cause motor and cognitive neuronal damage. Once in the CNS, T. cruzi triggers immune responses that the purinergic system can regulate. Treatment for CD is based on benznidazole (BNZ); however, this agent has negative side-effects and is toxic to the host. For this reason, we investigated whether resveratrol (RSV), a potent antioxidant and neuroprotective molecule, would modulate purinergic signaling and RSV alone or in combination with BNZ would prevent changes in purinergic signaling and oxidative damage caused by T. cruzi. We infected mice with T. cruzi and treated them with RSV or BNZ for 8 days. Increases in ATP and ADP hydrolysis by NTPDase in the total cortex of infected animals were observed. The treatment with RSV in infected group diminished ATP, ADP, and AMP hydrolysis compared to infected group. The combination of RSV + BNZ decreased AMP hydrolysis in infected animals compared to the INF group, exerting an anti-inflammatory effect. RSV acted as a neuroprotector, decreasing adenosine levels. Infected animals presented an increase of P2X7 and A2A density of purine receptors. RSV reduced P2X7 and A2A and increased A1 density receptors in infected animals. In addition, infected animals showed higher TBARS and reactive oxygen species (ROS) levels than control. RSV diminished ROS levels in infected mice, possibly due to antioxidant properties. In short, we conclude that resveratrol could act as a neuroprotective molecule, probably preventing inflammatory changes caused by infection by T. cruzi, even though the mice experienced high levels of parasitemia.

Neuroprotective role of resveratrol mediated by purinergic signalling in cerebral cortex of mice infected by Toxoplasma gondii.

The central nervous system of the intermediate host plays a central role in lifelong persistence of Toxoplasma gondii as well as the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised individuals. The purinergic system has been implicated in a wide range of immunological pathways for controlling intracellular responses to pathogens, including T. gondii. In the present study, we investigated the effect of resveratrol (RSV) on ectonucleotidases, adenosine deaminase (ADA), and purinergic receptors during chronic infection by T. gondii. For this study, Swiss mice were divided into control (CTL), resveratrol (RSV), infected (INF), and INF+RSV groups. The animals were orally infected with the VEG strain and treated with RSV (100 mg/kg, orally). Ectonucleotidase activities, P2X7, P2Y1, A1, and A2A purinergic receptor density, ROS, and thiobarbituric acid reactive substances levels were measured in the cerebral cortex of mice. T. gondii infection increased NTPDase and reduced ADA activities. Treatment with RSV also affected enzymes hydrolysing extracellular nucleotides and nucleosides. Finally, RSV affected P1 and P2 purinergic receptor expression during T. gondii infection. Overall, RSV-mediated beneficial changes in purinergic signalling and oxidative stress, possibly improving cerebral cortex homeostasis in T. gondii infection.

Relation between acetylcholinesterase and Na+, K+-ATPase activities with impaired memory of mice experimentally infected by Trypanosoma cruzi.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na+, K+-ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na+, K+-ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na+, K+-ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na+, K+-ATPase activities may be considered a mechanism involved in disease pathogenesis.

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection.

Experimental cerebral malaria pathogenesis--hemodynamics at the blood brain barrier.

Cerebral malaria claims the lives of over 600,000 African children every year. To better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, Plasmodium berghei ANKA (PbA) infected CBA/CaJ mice, which develop experimental cerebral malaria (ECM), and P. yoelii 17XL (PyXL) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. Using a combination of intravital imaging and flow cytometry, we show that significantly more CD8(+) T cells, neutrophils, and macrophages are recruited to postcapillary venules during ECM compared to hyperparasitemia. ECM correlated with ICAM-1 upregulation on macrophages, while vascular endothelia upregulated ICAM-1 during ECM and hyperparasitemia. The arrest of large numbers of leukocytes in postcapillary and larger venules caused microrheological alterations that significantly restricted the venous blood flow. Treatment with FTY720, which inhibits vascular leakage, neurological signs, and death from ECM, prevented the recruitment of a subpopulation of CD45(hi) CD8(+) T cells, ICAM-1(+) macrophages, and neutrophils to postcapillary venules. FTY720 had no effect on the ECM-associated expression of the pattern recognition receptor CD14 in postcapillary venules suggesting that endothelial activation is insufficient to cause vascular pathology. Expression of the endothelial tight junction proteins claudin-5, occludin, and ZO-1 in the cerebral cortex and cerebellum of PbA-infected mice with ECM was unaltered compared to FTY720-treated PbA-infected mice or PyXL-infected mice with hyperparasitemia. Thus, blood brain barrier opening does not involve endothelial injury and is likely reversible, consistent with the rapid recovery of many patients with CM. We conclude that the ECM-associated recruitment of large numbers of activated leukocytes, in particular CD8(+) T cells and ICAM(+) macrophages, causes a severe restriction in the venous blood efflux from the brain, which exacerbates the vasogenic edema and increases the intracranial pressure. Thus, death from ECM could potentially occur as a consequence of intracranial hypertension.

Cerebral complement C1q activation in chronic Toxoplasma infection.

Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary, our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.

Characteristic CT and MR imaging findings of cerebral paragonimiasis.

BACKGROUND AND PURPOSE: The early diagnosis of cerebral paragonimiasis (CP) is essential for a good prognosis. We seek to provide references for early diagnosis by analyzing the imaging characteristics of cerebral paragonimiasis. MATERIALS AND METHODS: Images of 27 patients with CP (22 males and 5 females; median age 20.3 years; range: 4 to 47 years) were retrospectively evaluated. All patients underwent head computed tomography (CT) scans; 22 patients underwent conventional magnetic resonance imaging (MRI) sequences, including contrast-enhanced MRI for 20 patients and diffusion-weighted-imaging (DWI) for 1 patient. The diagnosis was confirmed based on a positive antibody test using enzyme-linked immunosorbent assay (ELISA) for paragonimiasis in the serum. RESULTS: The most common imaging findings of CP were isodense or hypodense lesions combined with extensive hypodense areas of perilesional edema on CT scans and a large mass composed of multiple ring-shaped lesions with surrounding edema on MRI images. The conglomeration of multiple ring-shaped lesions (n=11 patients), "tunnel signs" (n=12 patients) and worm-eaten signs (n=5 patients) were characteristic of most CP images. In 14 patients, contrast-enhanced MRI showed varying degrees of contrast enhancement combined with adjacent meningeal enhancement (n=10). CONCLUSIONS: A large mass comprising multiple ring-shaped lesions of different sizes, "tunnel signs" and worm-eaten signs with surrounding edema are the most characteristic features of CP. Extensive invasions of the adjacent meninges and ventricular wall (19 patients), multiple intracerebral lesions, bilateral hemispheric involvement, and lesion migration are other noteworthy imaging characteristics.

Imaging characteristics of cerebral sparganosis with live worms.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of cerebral sparganosis to improve the accuracy of diagnosing cerebral sparganosis with medical imaging modalities. MATERIALS AND METHODS: This was a retrospective study of CT and MRI features of 12 patients with cerebral sparganosis. A comparative analysis between imaging findings, and intraoperative and postoperative pathological findings was performed. RESULTS: A total of 20 lesions were observed in 12 patients with 5 patients having a solitary lesion. CT and MRI imaging showed worm-body sign in 5 patients (41.7%), tunnel-sign in 5 patients (41.7%), migration sign in 7 patients (58.3%), worm-shaped enhancement in 4 patients (33.3%), bead-shaped or ring-shaped enhancement in 5 patients (41.7%), irregular or nodular enhancement in 3 patients (25%), meningeal enhancement in 2 patients (16.6%), intracranial hemorrhage in 2 patients (16.6%), brain parenchymal edema in 10 patients (83.3%), cerebral white matter degeneration in 11 patients (91.7%), negative mass effect in 10 patients (83.3%), and punctuate calcification in 3 patients (25%). Among the 4 patients with live worm, CT and MRI showed worm-body sign in 3 patients (75%), tunnel-sign in 3 patients (75%), migration sign in 3 patients (75%), and worm-shaped enhancement in 2 patients (50%). CONCLUSION: Cerebral sparganosis with live worm exhibits several distinguishing imaging characteristics, which reflect the pathological changes and can improve the diagnosis of cerebral sparganosis.

Cortical pathology in multiple sclerosis patients with epilepsy: a 3 year longitudinal study.

INTRODUCTION: The cause of epilepsy in multiple sclerosis (MS) has not yet been elucidated. The relevance of cortical pathology (cortical lesions and thickness) in MS patients with and without epilepsy was evaluated in a longitudinal study. METHODS: 32 relapsing-remitting MS patients with epilepsy (RRMS/E) and 60 matched RRMS patients without epilepsy were included in a 3 year longitudinal study. The following clinical and MR parameters were analysed: Expanded Disability Status Scale (EDSS), cognitive score (CS), cortical lesion (CL) number and volume, grey matter fraction (GMf), global cortical thickness (CTh), T2 white matter lesion volume (T2WMLV), new CLs and new WM lesions. RESULTS: At baseline (T0), CLs were observed in 27/32 (84.4%) RRMS/E and in 26/60 (43.3%) RRMS (p<0.001) patients, and the RRMS/E group had a higher number (10.2 ± 8.9 vs 4.5 ± 2.4; p<0.001) and total volume (2.0 ± 1.3 vs 0.7 ± 0.8 cm(3); p<0.001) of CLs compared with the RRMS group. No significant difference in T2WMLV was observed. Global CTh was lower in RRMS/E (2.12 ± 0.19 vs 2.35 ± 0.14 mm; p<0.001), and this group also showed a decline in cognition (CS 10.9 ± 6.3 vs 6.2 ± 3.5; p<0.001). After 3 years (T1), the RRMS/E group had a higher accumulation of new CLs (3.4 ± 3.2 vs 1.2 ± 1.1; p<0.001) and faster reduction of GMf (p=0.022) while the two groups did not differ in the number of new WM and new Gad+ lesions. DISCUSSION: RRMS/E had a more severe and rapidly evolving cortical pathology (CLs and atrophy) compared with RRMS without epilepsy. The RRMS/E group was also characterised by more pronounced cognitive decline, higher EDSS and higher prevalence of men.

Atypical radiological findings in cerebral hydatid disease.

Cerebral hydatid disease is very rare, representing only 2% of all cerebral space occupying lesions. The diagnosis is usually based on a pathognomonic CT pattern. Exceptionally, the image is atypical raising suspicion of many differential diagnoses such as intracerebral infectious, vascular lesions, or tumors. We report 2 atypical cases of cerebral hydatid cysts diagnosed in a 21, and a 24-year-old woman. The CT scan results suggest oligodendroglioma in the first case and brain abscess in the second. An MRI was helpful in the diagnosis of the 2 cases. Both patients underwent successful surgery with a good outcome. The hydatid nature of the cyst was confirmed by histology in both cases.

Joint analysis of structural and perfusion MRI for cognitive assessment and classification of Alzheimer's disease and normal aging.

Structural magnetic resonance imaging (MRI) of brain tissue loss and physiological imaging of regional cerebral blood flow (rCBF) can provide complimentary information for the characterization of brain disorders, such as Alzheimer's disease (AD) but studies into gains in classification power for AD using these image modalities jointly have been limited. Our aim in this study was to determine the joint contribution of structural and perfusion-weighted imaging for the classification of AD in a cross-sectional study using an integrated multimodality MRI processing framework and a cortical surface-based analysis approach. We used logistic regression analysis to determine sequentially the value of cortical thickness, rCBF, and cortical thickness and rCBF jointly for classification for diagnosis of AD compared to controls. We further tested the extent to which cortical thinning and reduced rCBF explain individually or together variability in dementia severity. Separate analysis of structural MRI and perfusion-weighted MRI data yielded the well-established pattern of cortical thinning and rCBF reduction in AD, affecting predominantly temporo-parietal brain regions. Using structural MRI and perfusion-weighted MRI jointly indicated that cortical thinning dominated the classification of AD and controls without significant contributions from rCBF. However there was also a positive interaction between reduced rCBF and cortical thinning in the right superior temporal sulcus, implying that structural and physiological brain alterations in AD can be complementary. Compared to reduced rCBF, regional cortical thinning better explained the variability in dementia severity. In conclusion, structural brain alterations compared to physiological variations are the dominant features of MRI in AD.

Frequent development of inflammatory lesions and lymphoid foci in the kidneys of Japanese wild crows (Corvus macrorhynchos and Corvus corone) as a result of the entry of causal agents via the renal portal blood.

Although the increase in the number of wild crows is causing social problems in urban areas, crows play an increasingly important role in monitoring serious infectious diseases, such as highly pathogenic avian influenza and West Nile fever. To gain a better understanding of normal conditions and common disorders in crows, we conducted a retrospective study of wild crows captured in central Japan in the 1990s and examined the necropsy findings from 166 jungle crows (Corvus macrorhynchos) and 74 carrion crows (Corvus corone). We found frequent development of lymphoid foci and inflammatory lesions in the kidneys of both species of crows. These findings were unrelated to place or date of capture, indicating the universality of renal lesion developments in the Corvus species. In the kidneys, suppurative granulomas were concentrated in the renal cortex and the vein wall, indicating the haematoegenous spread of causal agents. However, the glomeruli remained intact, unlike the spreading of causal agents via arterial blood, which strongly suggested the renal portal blood as a possible entry route of causal agents. The renal lymphoid foci showed the same distribution as the granulomas, supporting the possibility of external agents entering through renal portal blood. We also identified types of parasites in Japanese wild crows by means of histopathological analysis. We hope that our data will contribute to the appropriate evaluation and a better understanding of pathological conditions in Japanese wild crows.

Neurocysticercosis causing sudden death.

Neurocysticercosis causes significant morbidity due to neurologic manifestations including seizures. Sudden unexpected death in epilepsy (SUDEP) is responsible for mortality associated with seizure disorders. This case highlights death from neurocysticercosis and possible SUDEP in a nonendemic country.

Concomitant Isolation of Primary Astrocytes and Microglia for Protozoa Parasite Infection.

Astrocytes and microglia are the most abundant glial cells. They are responsible for physiological support and homeostasis maintenance in the central nervous system (CNS). The increasing evidences of their involvement in the control of infectious diseases justify the emerging interest in the improvement of methodologies to isolate primary astrocytes and microglia in order to evaluate their responses to infections that affect the CNS. Considering the impact of Trypanosoma cruzi (T. cruzi) and Toxoplasma gondii (T. gondii) infection in the CNS, here we provide a method to extract, maintain, dissociate and infect murine astrocytes and microglia cells with protozoa parasites. Extracted cells from newborn cortices are maintained in vitro for 14 days with periodic differential media replacement. Astrocytes and microglia are obtained from the same extraction protocol by mechanical dissociation. After phenotyping by flow cytometry, cells are infected with protozoa parasites. The infection rate is determined by fluorescence microscopy at different time points, thus enabling the evaluation of differential ability of glial cells to control protozoan invasion and replication. These techniques represent simple, cheap and efficient methods to study the responses of astrocytes and microglia to infections, opening the field for further neuroimmunology analysis.

Metabolomic signature of mouse cerebral cortex following Toxoplasma gondii infection.

BACKGROUND: The protozoan parasite Toxoplasma gondii infects and alters the neurotransmission in cerebral cortex and other brain regions, leading to neurobehavioral and neuropathologic changes in humans and animals. However, the molecules that contribute to these changes remain largely unknown. METHODS: We have investigated the impact of T. gondii infection on the overall metabolism of mouse cerebral cortex. Mass-spectrometry-based metabolomics and multivariate statistical analysis were employed to discover metabolomic signatures that discriminate between cerebral cortex of T. gondii-infected and uninfected control mice. RESULTS: Our results identified 73, 67 and 276 differentially abundant metabolites, which were involved in 25, 37 and 64 pathways at 7, 14 and 21 days post-infection (dpi), respectively. Metabolites in the unsaturated fatty acid biosynthesis pathway were upregulated as the infection progressed, indicating that T. gondii induces the biosynthesis of unsaturated fatty acids to promote its own growth and survival. Some of the downregulated metabolites were related to pathways, such as steroid hormone biosynthesis and arachidonic acid metabolism. Nine metabolites were identified as T. gondii responsive metabolites, namely galactosylsphingosine, arachidonic acid, LysoSM(d18:1), L-palmitoylcarnitine, calcitetrol, 27-Deoxy-5b-cyprinol, L-homophenylalanine, oleic acid and ceramide (d18:1/16:0). CONCLUSIONS: Our data provide novel insight into the dysregulation of the metabolism of the mouse cerebral cortex during T. gondii infection and have important implications for studies of T. gondii pathogenesis.

Albendazole therapy for single small enhancing CT lesions (SSECTL) in the brain in epilepsy.

BACKGROUND: Single small enhancing CT lesions (SSECTL) of the brain with or without perifocal oedema are common in patients with symptomatic epilepsy in India. Solitary cysticercus granuloma, a benign form of parenchymal neurocysticercosis, is considered to be the most common aetiology for SSECTL. Definite information is lacking regarding the effectiveness of antiparasitic treatment on resolution of these lesions and on long term seizure recurrence. OBJECTIVE: To evaluate the response to albendazole treatment in patients who had SSECTL and new onset seizures treated with antiepileptic drugs (AED) in a prospective clinical trial. METHODS: 43 patients who presented with new onset seizures and were documented to have SSECTL were alternatively allocated to receive albendazole 15 mg/kg/day for 2 weeks or no cysticidal therapy. All patients were treated with AED and followed for at least 6 months for seizure recurrence, and serial CT scans were obtained at 4 weeks, 3 months and at study completion. RESULTS: 28 (65%) patients were aged 5-25 years and 31 (72%) presented clinically with partial motor seizures with or without generalisation. Most of the SSECTL were ring lesions (75%) and located in and around the sensory-motor cortex at the gray-white junction (65%). In the albendazole group, 56% of patients compared with 35% in the control group showed resolution of SSECTL (p = 0.154) at 1 month. 22 of 23 patients (95.6%), who received albendazole, compared with 14 of 20 patients (70%) in the control group, demonstrated radiological resolution on study completion (p = 0.03). Punctate residual calcification and seizure recurrence were observed in four patients (9.3%) in the control group and in three (7%) patients in the albendazole group (p = 0.47). CONCLUSIONS: In patients presenting with seizures due to single viable parenchymal neurocysticercosis, albendazole hastens the resolution of SSECTL if treatment is given in the early phase of the illness.

Unusual MRI findings in a patient with history of frontal fracture and skin infestation by fly larvae, as a possible sign of intracerebral myiasis.

We report a case of an 11-year-old columbian immigrant with mild non-specific cephalalgia. He had a previous history of frontal fracture and skin infestation caused by Dermatobia hominis larvae. MRI performed revealed multiple subependymal and intraventricular lesions with concentric blooming artifacts and moderate hydrocephalus. Based on his previous history, intracerebral myiasis diagnosis was suggested. His mother denied any kind of diagnostic surgery or treatment. To the best of our knowledge, this is the first MRI report of a possible intracerebral myiasis, an exceedingly rare entity.

A survey of Taenia multiceps coenurosis in Sardinian sheep.

A survey was carried out to assess the occurrence of Coenurus cerebralis infection in Sardinian sheep. A prevalence of 0.35% was observed when 566 regularly slaughtered sheep were examined. However, in 120 sheep with suspected symptoms of coenurosis examined from November 2001 to October 2002, a total of 299 cerebral coenurosis lesions were observed with an incidence of 1% per year. Lesions were classified as migratory, cystic and secondary. Most migratory lesions were found in sheep aged 3-6 months. Cavitary lesions containing cysts in different developing stages were found with high incidence per year in sheep aged 7-12 months. Secondary lesions due to the development of Coenurus were most frequent in sheep aged 19-36 months. Most sheep were found infected in spring and in early summer, between March and June. Most lesions were located in the cortex. The mean number of protoscolices per cyst was 149 (range 10-370).

Oral cysticercosis.

Cysticercosis is the result of infection with the larval stage of the tapeworm, Taenia solium. The parasite may settle at any site in the body without causing symptoms, which arise almost exclusively from the involvement of brain or eye, and this may occur several years after infection. Cysticercosis is one of the leading causes of acquired epilepsy in Latin America, parts of Asia, and Africa. More cases are being reported in other countries as a result of immigration from endemic areas. Cysticercosis may cause cystic swellings or nodules in the mouth, and these may be the only evidence of the disease. We present a healthy patient who had multiple intraoral cystic swellings that were diagnosed as cysticercosis in a biopsy specimen. Subsequent investigations showed cysticerci in the brain.

Leishmania amazonensis infection induces behavioral alterations and modulates cytokine and neurotrophin production in the murine cerebral cortex.

Neurological symptoms have been associated with Leishmania infection, however little is known about how the nervous system is affected in leishmaniasis. This work aimed to analyze parasitic load, production of cytokines/neurotrophins in the prefrontal cortex and behavioral changes in BALB/c mice infected with Leishmania amazonensis. At 2 and 4months post-infection, infected mice showed a decrease in IFN-γ, IL-1, IL-6, IL-4, IL-10 cytokines and BDNF and NGF neurotrophins in prefrontal cortex associated with increased anxiety behavior. Parasite DNA was found in brain of all animals at 4months post-infection, when the levels of IBA-1 (activated macrophage/microglia marker) and TNF-α was increased in the prefrontal cortex. However TNF-α returned to normal levels at 6months post-infection suggesting a neuroprotective mechanism.