Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability.

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.

Transcranial Doppler findings in a population with clinical probable reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To describe transcranial Doppler (TCD) findings in a population with clinical probable RCVS. Exploratory objectives included the study of clinical characteristics of probable RCVS patients with and without spasm detected by TCD. METHODS: Cross-sectional cohort study of patients with thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) of our neurology and headache center between 2010 and 2019, selecting patients with clinical diagnosis of probable RCVS (negative angiography study) by ICHD-3 criteria and with at least two TCD studies. RESULTS: From 114 TCH patients, 36/114 had probable RCVS by ICHD-3 criteria and had at least two TCD studies available. The mean age at RCVS onset was 42.9years (21-72years); 29/36 (80.6%) were female, 7/28 (25%) had cardiovascular risk factors and 20/36 (55.6%) had history of migraine. Most common triggers were stressful emotion, drugs, valsalva maneuvers and sexual activity. Five/36 (13.9%) had complications and 3/36 (8.3%) had late recurrence. Initial TCD was performed on average of 16 (6-26) days after headache onset. Twenty-nine had vasospasm on TCD, presenting mean flow velocity of MCA (VMCA) of 135.7±17.0cm/s and mean maximum VMCA of 138.3±17.2. Vasospasm was mild in 21/29 patients (72.4%) and moderate in 8/29 (27.6%). Complete VMCA normalization occurred on average 41 (30-70) days after headache onset and 24 (11-47) days after initial TCD. The group of patients with vasospasm detected by TCD had more female patients (26/29, 89.7% vs. 3/7, 42.8%, P=0.016), and more TCH attacks (mean of 3.6 vs. 2.14, P=0.049). CONCLUSION: TCD may be a useful tool in the identification of vasospasm in patients with probable RCVS, supporting the diagnosis of RCVS in patients presenting with recurrent TCH without SAH.

Blood biomarkers associated with inflammation predict poor prognosis in cerebral venous thrombosis:: a multicenter prospective observational study.

BACKGROUND AND PURPOSE: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. METHODS: Pathophysiology of Venous Infarction-Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)-6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. RESULTS: Interleukin-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL-6: OR = 1.28, 95% CI: 1.05-1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4-1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010-3.051, P = 0.029). Baseline IL-6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). CONCLUSIONS: Increased baseline levels of NLR, CRP and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization.

"Headache yesterday" at work. Pilot study of headache impact in an active workforce.

A pilot (single company) questionnaire-based on-line survey aimed to evaluate headache related impact and estimate work-related productivity loss. Participation rate was 5.4%, respondents were mostly female (254, 78.9%) 37.6 years old on average, 63.9% had migraine. Headache point-prevalence on workdays was 14.6%. Lost productivity was 27.7%, considering 2h of absenteeism and 37.5% of over 50% productivity-loss to headache. Sixty percent of employees intended to compensate for lost work, at the expense of family and social time. Total yearly cost of headache in this sample was 262.500 €, 94% indirect wage-loss cost, which extrapolates to 485M€ at a national level.

Headache service quality evaluation: implementation of quality indicators in primary care in Europe.

BACKGROUND: Lifting The Burden (LTB) and European Headache Federation (EHF) have developed a set of headache service quality indicators, successfully tested in specialist headache centres. Their intended application includes all levels of care. Here we assess their implementation in primary care. METHODS: We included 28 primary-care clinics in Germany (4), Turkey (4), Latvia (5) and Portugal (15). To implement the indicators, we interviewed 111 doctors, 92 nurses and medical assistants, 70 secretaries, 27 service managers and 493 patients, using the questionnaires developed by LTB and EHF. In addition, we evaluated 675 patients' records. Enquiries were in nine domains: diagnosis, individualized management, referral pathways, patient education and reassurance, convenience and comfort, patient satisfaction, equity and efficiency of headache care, outcome assessment and safety. RESULTS: The principal finding was that Implementation proved feasible and practical in primary care. In the process, we identified significant quality deficits. Almost everywhere, histories of headache, especially temporal profiles, were captured and/or assessed inaccurately. A substantial proportion (20%) of patients received non-specific ICD codes such as R51 ("headache") rather than specific headache diagnoses. Headache-related disability and quality of life were not part of routine clinical enquiry. Headache diaries and calendars were not in use. Waiting times were long (e.g., about 60 min in Germany). Nevertheless, most patients (> 85%) expressed satisfaction with their care. Almost all the participating clinics provided equitable and easy access to treatment, and follow-up for most headache patients, without unnecessary barriers. CONCLUSIONS: The study demonstrated that headache service quality indicators can be used in primary care, proving both practical and fit for purpose. It also uncovered quality deficits leading to suboptimal treatment, often due to a lack of knowledge among the general practitioners. There were failures of process also. These findings signal the need for additional training in headache diagnosis and management in primary care, where most headache patients are necessarily treated. More generally, they underline the importance of headache service quality evaluation in primary care, not only to identify-quality failings but also to guide improvements. This study also demonstrated that patients' satisfaction is not, on its own, a good indicator of service quality.

Headache service quality: the role of specialized headache centres within structured headache services, and suggested standards and criteria as centres of excellence.

In joint initiatives, the European Headache Federation and Lifting The Burden have described a model of structured headache services (with their basis in primary care), defined service quality in this context, and developed practical methods for its evaluation.Here, in a continuation of the service quality evaluation programme, we set out ten suggested role- and performance-defining standards for specialized headache centres operating as an integral component of these services. Verifiable criteria for evaluation accompany each standard. The purposes are five-fold: (i) to inspire and promote, or stimulate the establishment of, specialized headache centres as centres of excellence; (ii) to define the role of such centres within optimally structured and organized national headache services; (iii) to set out criteria by which such centres may be recognized as exemplary in their fulfilment of this role; (iv) to provide the basis for, and to initiate and motivate, collaboration and networking between such centres both nationally and internationally; (v) ultimately to improve the delivery and quality of health care for headache.

Sequential brief neuropsychological evaluation of migraineurs is identical to controls.

BACKGROUND: Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine. OBJECTIVE: To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications. METHOD: Assembly of the battery that was then applied twice within 6 weeks to interictal migraineurs and matched healthy controls. RESULTS: Migraine patients (n = 24) and controls (n = 24) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P = 0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores. CONCLUSIONS: Interictal migraineurs and controls performance is identical in a brief cognitive battery focused on executive functions. Repeated applications produced a practice effect that was quantified.

Antifungal effect of (R) and (S)-citronellal enantiomers and their predictive mechanism of action on Candida albicans from voriconazole-resistant onychomycoses.

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-ß-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

Lower low density lipoprotein cholesterol associates to higher mortality in non-diabetic heart failure patients.

Background: In patients with established heart failure (HF) low total cholesterol levels associate with worse prognosis. Evidence concerning the impact of Low-density lipoprotein cholesterol (LDL-c) in HF is scarce. We aimed to evaluate the prognostic impact of LDL-c in patients with HF, both with and without diabetes mellitus (DM). Methods: We retrospectively analyzed outpatients with chronic HF with systolic dysfunction followed in our HF clinic from January/2012 to May/2018. LDL-c was calculated using the Friedewald's formula. Patients without a complete lipid profile were excluded. The endpoint under analysis was all-cause mortality. Patients were followed until January/2021. A Cox-regression analysis was used to study the prognostic impact of LDL-c. The LDL-c cut-off used was 100 mg/dL (mean value). Analysis was stratified according to the coexistence of DM. Multivariate models were built adjusting for age, sex, coronary artery disease, atherosclerotic non-coronary artery disease, arterial hypertension, smoking status, statin use, severity of systolic dysfunction, creatinine clearance and evidence-based therapy. Results: We studied 522 chronic HF patients, mean age was 70 years, 66.5% males. Severe systolic dysfunction was present in 42.7%, 30.5% had coronary heart disease, 60.5% had arterial hypertension, 41.6% had DM. A total of 92.0% were treated with beta blocker, 87.5% with an ACEi/ARB and 29.1% with a MRA. During a median follow-up of 53 (interquartile range 33-73) months, 235 (45%) patients died. Patients with LDL-c ≤100 mg/dL presented increased multivariate-adjusted risk of all-cause mortality: HR = 1.58 (95% CI: 1.08-2.30), p = 0.02. When patients were stratified according to DM, LDL-c ≤100 mg/dL was independently associated with increased death risk - HR = 1.55 (95% CI:1.05-2.30), p = 0.03 in patients without DM; in patients with DM no association was detected - multivariate-adjusted HR = 1.18 (95% CI: 0.77-1.80), p = 0.44. Conclusion: Non-DM HF patients with LDL-c>100 mg/dL have a 35% reduction in the mortality risk when compared with those with lower values. The "cholesterol paradox" in HF also applies to LDL-c in non-DM patients.

Impact of mother donor, peripheral blood stem cells and measurable residual disease on outcomes after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in children with acute leukaemia.

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

Neuropsychiatric side-effects of lidocaine: examples from the treatment of headache and a review.

Lidocaine has been used in treatment of patients with refractory headache. Personal observations of neuropsychiatric toxicity in these patients led us to review our cases and the literature systematically for lidocaine side-effects, especially neuropsychiatric symptoms. In our series of 20 patients, side-effects were observed in all, the most frequent being neuropsychiatric (75%) and cardiological (50%). When reviewing published series on intravenous lidocaine use, reports of side-effects range from 0 to 100%, with neuropsychiatric symptoms being reported in 1.8-100%. Thirty-six case reports of lidocaine-induced psychiatric symptoms were also analysed. Psychiatric symptoms of toxicity were similar in most patients, despite their differing ages, pathologies, co-therapies and lidocaine dosages. In conclusion, lidocaine neuropsychiatric toxicity has a well-recognized stereotypical clinical presentation that is probably unrecognized in headache series. As lidocaine represents an emerging alternative therapy in headache, particularly in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, clinicians and patients should be aware of the extent of this problem.

Detection of charge distributions in insulator surfaces.

Charge distribution in insulators has received considerable attention but still poses great scientific challenges, largely due to a current lack of firm knowledge about the nature and speciation of charges. Recent studies using analytical microscopies have shown that insulators contain domains with excess fixed ions forming various kinds of potential distribution patterns, which are also imaged by potential mapping using scanning electric probe microscopy. Results from the authors' laboratory show that solid insulators are seldom electroneutral, as opposed to a widespread current assumption. Excess charges can derive from a host of charging mechanisms: excess local ion concentration, radiochemical and tribochemical reactions added to the partition of hydroxonium and hydronium ions derived from atmospheric water. The last factor has been largely overlooked in the literature, but recent experimental evidence suggests that it plays a decisive role in insulator charging. Progress along this line is expected to help solve problems related to unwanted electrostatic discharges, while creating new possibilities for energy storage and handling as well as new electrostatic devices.

C4d-the witness of humoral rejection.

OBJECTIVE: Acute antibody-mediated (humoral) rejection is a major cause of morbidity, graft loss, and mortality among heart transplant patients. Herein we have presented our experience using C4d to characterize humoral rejection. MATERIALS AND METHODS: All nonformalin-fixed cardiac graft biopsies (protocol or emergency) received between May 2007 and May 2008 were examined by immunofluorescence for C4d. RESULTS: One hundred twelve endomyocardial biopsies from 25 transplanted patients included 20 males and 5 females of ages ranging from 3 to 71 years. The number of biopsies per subject varied from 1 to 11; the timespan between transplantation and the diagnostic biopsies ranged from days to 8 years. Thirteen biopsies showed acute humoral rejection (intramyocardial capillaries positive for C4d); 31, acute cellular rejection (grades 1R, 2R); 7, both humoral and cellular rejection; and 1, acute humoral rejection and allograft vasculopathy. Some of the positive biopsies belonged to the same person, and some to transplanted individuals with signs and symptoms suggestive of rejection, while others did not. The persistence of humoral rejection, despite the disappearance of a cellular component, correlated with slower clinicoechocardiographic improvement. CONCLUSIONS: C4d positivity is a morphologic sign of humoral rejection. It may hasten the appearance and/or worsening of allograft vasculopathy independent of patient age or posttransplantation time.

Silver nanoparticles coated with dodecanethiol used as fillers in non-cytotoxic and antifungal PBAT surface based on nanocomposites.

In the present study, we report the preparation of antifungal and non-cytotoxic polymer nanocomposites with potential application in biomedical materials. Dodecanethiol-protected silver nanoparticles (AgNPs-DDT) were synthesized by a reduction/precipitation method and dispersed in chloroform to obtain stable colloidal dispersions. PBAT-based nanocomposites containing 0.25, 0.5 and 2 wt% AgNPs-DDT were prepared by casting method. The incorporation of AgNPs-DDT in PBAT matrix resulted in nanocomposites which combine improved mechanical performance and antifungal properties with a non-cytotoxic characteristic.

Serratia liquefaciens Infection of a Previously Excluded Popliteal Artery Aneurysm.

INTRODUCTION: Popliteal artery aneurysms (PAAs) are rare in the general population, but they account for nearly 70% of peripheral arterial aneurysms. There are several possible surgical approaches including exclusion of the aneurysm and bypass grafting, or endoaneurysmorrhaphy and interposition of a prosthetic conduit. The outcomes following the first approach are favorable, but persistent blood flow in the aneurysm sac has been documented in up to one third of patients in the early post-operative setting. Complications from incompletely excluded aneurysms include aneurysm enlargement, local compression symptoms, and sac rupture. Notably infection of a previously excluded and bypassed PAA is rare. This is the third reported case of PAA infection after exclusion and bypass grafting and the first due to Serratia liquefaciens. METHODS: Relevant medical data were collected from the hospital database. RESULTS: This case report describes a 54 year old male patient, diagnosed with acute limb ischaemia due to a thrombosed PAA, submitted to emergency surgery with exclusion and venous bypass. A below the knee amputation was necessary 3 months later. Patient follow-up was lost until 7 years following surgical repair, when he was diagnosed with aneurysm sac infection with skin fistulisation. He had recently been diagnosed with alcoholic hepatic cirrhosis Child-Pugh Class B. The patient was successfully treated by aneurysm resection, soft tissue debridement and systemic antibiotics. CONCLUSION: PAA infection is a rare complication after exclusion and bypass procedures but should be considered in any patient with evidence of local or systemic infection. When a PAA infection is diagnosed, aneurysmectomy, local debridement, and intravenous antibiotic therapy are recommended. The "gold standard" method of PAA repair remains controversial. PAA excision or endoaneurysmorrhaphy avoids complications from incompletely excluded aneurysms, but is associated with a high risk of neurological damage.

Coronary Stent Embolisation to an Iatrogenic Arteriovenous Fistula: An Unexpected Complication.

INTRODUCTION: Systemic embolisation of stents represents a rare complication of coronary interventions. REPORT: The case of a patient with peripheral embolisation of a coronary stent while undergoing a coronary procedure for an ischaemic event is reported. The stent lodged at a previously created iatrogenic fistula joining the profunda femoral artery and the common femoral vein. An endovascular attempt was ineffective in treating this complication. The stent was removed surgically and the fistula repaired. DISCUSSION: This unusual clinical setting of stent embolisation concomitant to an iatrogenic arteriovenous femoral fistula is reported.

Microstructure and Hardness of Buffalo's Hoofs.

The aim of this study was to describe the microstructure of hoof capsules of the buffalo. In addition, the study emphasized the morphometric aspects of the horn tubules, the Vickers nanohardness of the dorsal and abaxial walls and sole of the digits of the thoracic and pelvic limbs of the buffalo. The abaxial wall in the thoracic and pelvic digits showed larger diameter of the horn tubules when compared to all dorsal wall and sole. In addition, the abaxial wall of the thoracic digits showed larger diameter of the horn tubules when compared with the pelvic digits. According to the three-dimensional microtomography, the dorsal wall was higher in density compared with the abaxial wall. The latter exhibited an intermediate density, while the sole showed the lowest density. The Vickers nanohardness test showed that there was no difference in hardness and resistance between the experienced regions. However, the elastic modulus was greater on the transversal section of the hoof capsule. In conclusion, the results of the current study show that modern technologies such as microtomography and subsequent imaging can be used to investigate details of the basic morphology in different regions of the buffalo's hoof.

Gamma-irradiated human amniotic membrane decellularised with sodium dodecyl sulfate is a more efficient substrate for the ex vivo expansion of limbal stem cells.

The gold standard substrate for the ex vivo expansion of human limbal stem cells (LSCs) remains the human amniotic membrane (HAM) but this is not a defined substrate and is subject to biological variability and the potential to transmit disease. To better define HAM and mitigate the risk of disease transmission, we sought to determine if decellularisation and/or γ-irradiation have an adverse effect on culture growth and LSC phenotype. Ex vivo limbal explant cultures were set up on fresh HAM, HAM decellularised with 0.5M NaOH, and 0.5% (w/v) sodium dodecyl sulfate (SDS) with or without γ-irradiation. Explant growth rate was measured and LSC phenotype was characterised by histology, immunostaining and qRT-PCR (ABCG2, ΔNp63, Ki67, CK12, and CK13). Ƴ-irradiation marginally stiffened HAM, as measured by Brillouin spectromicroscopy. HAM stiffness and γ-irradiation did not significantly affect the LSC phenotype, however LSCs expanded significantly faster on Ƴ-irradiated SDS decellularised HAM (p<0.05) which was also corroborated by the highest expression of Ki67 and putative LSC marker, ABCG2. Colony forming efficiency assays showed a greater yield and proportion of holoclones in cells cultured on Ƴ-irradiated SDS decellularised HAM. Together our data indicate that SDS decellularised HAM may be a more efficacious substrate for the expansion of LSCs and the use of a γ-irradiated HAM allows the user to start the manufacturing process with a sterile substrate, potentially making it safer. STATEMENT OF SIGNIFICANCE: Despite its disadvantages, including its biological variability and its ability to transfer disease, human amniotic membrane (HAM) remains the gold standard substrate for limbal stem cell (LSC) culture. To address these disadvantages, we used a decellularised HAM sterilised by gamma-irradiation for LSC culture. We cultured LSCs on fresh HAM, HAM decellularised with NaOH, HAM decellularised with sodium dodecyl sulfate (SDS) and HAM decellularised with SDS and sterilised with gamma-irradiation. We demonstrated that although HAM decellularised with SDS and sterilised with gamma-irradiation is significantly stiffer this does not affect LSC culture growth rate or the phenotype of cultured LSCs. We therefore recommend the use of SDS decellularised gamma-irradiated HAM in future LSC clinical trials.

Myenteric neuroprotective role of aspirin in acute and chronic experimental infections with Trypanosoma cruzi.

BACKGROUND: Experimental and clinical studies have shown that myenteric neuron cell death during infection with Trypanosoma cruzi mainly occurs in the esophagus and colon, resulting in megaesophagus and megacolon, respectively. Evidence suggests that the cyclooxygenase enzyme (COX) is involved in the T. cruzi invasion process. The use of low-dose aspirin (ASA), a COX-1/COX-2 inhibitor, has been shown to reduce infection with T. cruzi. Therefore, in this study, we evaluated the effects of treatment with low-dose ASA on myenteric colonic neurons during murine infection with T. cruzi. METHODS: Swiss mice were assigned into groups treated with either phosphate-buffered saline or low doses of ASA during the acute phase (20 mg/kg ASA) and chronic phase (50 mg/kg ASA) of infection with the Y strain of T. cruzi. Seventy-five days after infection, colon samples were collected to quantify inflammatory foci in histological sections and also general (myosin-V+ ), nitrergic, and VIPergic myenteric neurons in whole mounts. Gastrointestinal transit time was also measured. KEY RESULTS: Aspirin treatment during the acute phase of infection reduced parasitemia (P<.05). Aspirin treatment during the acute or chronic phase of the infection reduced the intensity of inflammatory foci in the colon, protected myenteric neurons from cell death and plastic changes, and recovered the gastrointestinal transit of mice infected with T. cruzi (P<.05). CONCLUSION & INFERENCES: Early and delayed treatment with low-dose ASA can reduce the morphofunctional damage of colonic myenteric neurons caused by murine T. cruzi infection.