Exploring the Cardiovascular Benefits of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: Expanding Horizons Beyond Diabetes Management.

Globally, cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality. The risk of cardiovascular disease is markedly increased in individuals with type 2 diabetes mellitus (T2DM), making managing cardiovascular health a top priority. Initially developed for their glucose-lowering properties, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a transformative class of pharmaceuticals with profound cardiovascular benefits that extend far beyond glycemic control. One of the most striking findings is the substantial reduction in major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality, observed in clinical trials evaluating SGLT2 inhibitors. These extraordinary cardioprotective effects are demonstrated by landmark trials such as EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58, which are discussed in detail. In addition, SGLT2 inhibitors have demonstrated positive outcomes in heart failure (HF) with reduced ejection fraction, which has led to their incorporation into HF treatment guidelines. SGLT2 inhibitors offer renoprotection by delaying the progression of diabetic kidney disease, reducing albuminuria, preserving glomerular filtration rates, and their immediate cardiovascular benefits. We investigate the potential mechanisms underlying these renal benefits, focusing on the role of hemodynamic alterations and intraglomerular pressure reduction. In addition, SGLT2 inhibitors have a distinct diuretic effect that can contribute to volume reduction and symptom alleviation in patients with heart failure (HF). This diuretic action, distinct from conventional diuretics, warrants additional research to optimize their use in T2DM and HF patients. The risk of euglycemic diabetic ketoacidosis, genital mycobacterial infections, and bone fractures are also discussed. Understanding these issues is essential for making educated clinical decisions. In conclusion, SGLT2 inhibitors have transcended their initial function as anti-diabetic agents to become essential components of cardiovascular and renal protection strategies in T2DM patients. Their diverse benefits, which include cardioprotection, renoprotection, and the potential for HF management, highlight their potential to transform cardiovascular medicine. Optimizing the use of SGLT2 inhibitors in clinical practice bears the promise of improved cardiovascular outcomes for patients with T2DM and beyond as we navigate this changing landscape.

Purification and biological analysis of antimicrobial compound produced by an endophytic Streptomyces sp.

Fungal phytopathogens and drug-resistant bacteria are two significant challenges in agriculture and public health, respectively. As a result, new sources of antimicrobial compounds are urgently needed. Taking into consideration these aspects, the present study was carried out to explore the antimicrobial activity of Streptomyces sp. SP5 against drug-resistant bacteria, especially methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus  and fungal phytopathogens. MRSA and VRE are both types of antibiotic-resistant bacteria that pose significant challenges to public health. In vitro analysis of the metabolites of Streptomyces sp. SP5 exhibited broad-spectrum antimicrobial activity against drug-resistant bacteria and phytopathogenic fungi. Further chemical investigation of the diethyl ether extract led to the isolation and purification of an antimicrobial compound. The structure of the purified compound was elucidated by performing detailed spectroscopic analysis including MS, IR, and NMR. The compound was identified as plicacetin. Plicacetin is a nucleoside antibiotic that has been reported for antibacterial activity against Gram-positive bacterium Mycobacterium tuberculosis. According to our knowledge, the present study is the first to demonstrate the antimicrobial properties of plicacetin against Fusarium oxysporum, Alternaria brassicicola, Fusarium solani, VRE and Bacillus subtilis. The outcome of the current study endorses that compound produced by Streptomyces sp. SP5 can be used as an antimicrobial agent against fungal phytopathogens and drug-resistant bacteria.

Eosinophilic Enteritis Flare-Up Mimicking Acute Gastroenteritis: A Rare Case.

Eosinophilic enteritis is a rare subset of eosinophilic gastrointestinal disorders. It typically presents with chronic symptoms of abdominal pain, nausea, vomiting, diarrhea, and ascites. However, the clinical presentation can vary due to acute flare-ups. Here, we present a case of eosinophilic enteritis in a young female patient with intractable vomiting and diarrhea, mimicking acute gastroenteritis in the absence of other gastrointestinal symptoms. This case illustrates the challenge of diagnosing acute and diverse presentations of eosinophilic enteritis. It also highlights the importance of promptly treating and confirming the diagnosis through urgent tissue histopathology in adolescents with unexplained vomiting and diarrhea.

Induction of systemic resistance in Solanum lycopersicum and Capsicum annum seedlings against Fusarium wilt by Streptomyces bioformulations.

Plant diseases induced by various phytopathogens pose a significant threat to contemporary agricultural systems around the world. In modern agriculture, the use of pesticides is still a valuable and effective method to control plant diseases. However, agrochemicals are becoming less popular because of the accretion of toxic compounds perilous and potentially hazardous to humans and the environment. Taking into consideration these aspects, the present study was conducted to explore the biocontrol potential of an endophytic Streptomyces sp. SP5 bioformulations against Fusarium wilt. Three bioformulations were prepared using cell biomass and different carriers, i.e., B1 (talc-kaolin), B2 (MgSO4/glycerol/Na-alginate/talc/Ca-lignosulfonate), and B3 (calcium carbonate/CMC/talc). Apart from antagonistic action against Fusarium wilt, the influence of bioformulations on plant growth and systemic resistance was investigated by analyzing morphological parameters (root length, shoot length, root weight, shoot weight), biochemical parameters (photosynthetic pigments, non-enzymatic antioxidants), and induction of antioxidative enzymes, e.g., catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and superoxide dismutase (SOD), in S. lycopersicum and C. annum seedlings. The results revealed that Streptomyces bioformulations effectively controlled Fusarium wilt in S. lycopersicum and C. annum (82.6-83.4% and 81.8-100%, respectively). Besides reducing disease prevalence, bioformulations significantly increased all the morphological parameters and increased the activity of antioxidative enzymes, i.e., CAT, APX, GPX, and SOD, in plants. The current findings display that bioformulations can be utilized as environment-friendly biocontrol agents against Fusarium wilt and also as plant growth promoters.

Insecticidal potential of endophytic Streptomyces sp. against Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) and biosafety evaluation.

Fruit flies of Tephritidae family pose a serious threat to cultivation of fruits and vegetables across the world. Among them, melon fruit fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) is a devastating pest of plants from Cucurbitaceae family. In a rising concern about the harmful effects associated with the use of chemical insecticides and development of resistance in pest insects, safer pest management strategies such as, use of biopesticides of microbial origin are being contemplated. Therefore, the present study aimed to evaluate the insecticidal potential of Streptomyces sp. SP5 protein extract against Z. cucurbitae. MTT assay, Ames mutagenicity, DNA nicking, and comet assay were conducted to determine the biosafety of protein extract. Second instar larvae of Z. cucurbitae were treated with various concentrations (1, 100, 200, 300, 400, and 500 µg/ml) of Streptomyces sp. SP5 protein extract. The protein extract showed significant larvicidal effects with LC50 value of 308.92 µg/ml. The percentage of adults emerged declined with increase in concentration. There was significant prolongation in developmental durations of the larvae. Various morphological aberrations in the form of deformed adults and pupae and decline in pupal weight were also observed. The nutritional physiology of the treated larvae was also adversely affected. The results from biosafety evaluation revealed antimutagenic and non-toxic nature of Streptomyces sp. proteins. This study indicates that Streptomyces sp. SP5 has the potential to be used as an ecologically safe biocontrol agent against Z. cucurbitae.

Efficacy of Molnupiravir for the Treatment of Mild or Moderate COVID-19 in Adults: A Meta-Analysis.

The aim of this meta-analysis is to evaluate the efficacy of molnupiravir among mild or moderate COVID-19 patients. This meta-analysis was reported according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Two authors independently performed a comprehensive search for relevant studies in PubMed, Cochrane Library, and Web of Science. The keywords used to search for relevant records were "Molnupiravir," "COVID-19," and "efficacy." This meta-analysis included studies that compared the effectiveness of molnupiravir with a placebo for COVID-19 treatment. The primary outcome assessed in this meta-analysis was the composite of hospitalization and all-cause mortality (30 days). In addition, we assessed all-cause mortality and hospitalization separately and the number of patients who tested negative for viral RNA on day five. A total of 10 studies were included in the meta-analysis. Among the 10 studies, five were randomized controlled trials and five were observational studies. Based on the results presented in the meta-analysis, it can be concluded that molnupiravir has a significant impact on reducing all-cause mortality and improving the proportion of patients who test negative for viral RNA on day five. The risk of hospitalization and composite outcome was also lower in molnupiravir-treated patients, although the difference was statistically insignificant. The subgroup analysis showed consistent results across all subgroups, indicating that the effect of molnupiravir is consistent regardless of patient characteristics.

Delayed Ventricular Septal Rupture Repair After Myocardial Infarction: An Updated Review.

Ventricular septal rupture (VSR) is a rare but serious complication that can occur after myocardial infarction (MI) and is associated with significant morbidity and mortality. The optimal management approach for VSR remains a topic of debate, with considerations including early versus delayed surgery, risk stratification, pharmacological interventions, minimally invasive techniques, and tissue engineering. The pathophysiology of VSR involves myocardial necrosis, inflammatory response, and enzymatic degradation of the extracellular matrix (ECM), particularly mediated by matrix metalloproteinases (MMPs). These processes lead to structural weakening and subsequent rupture of the ventricular septum. Hemodynamically, VSR results in left-to-right shunting, increased pulmonary blood flow, and potentially hemodynamic instability. The early surgical repair offers the advantages of immediate closure of the defect, prevention of complications, and potentially improved outcomes. However, it is associated with higher surgical risk and limited myocardial recovery potential during the waiting period. In contrast, delayed surgery allows for a period of myocardial recovery, risk stratification, and optimization of surgical outcomes. However, it carries the risk of ongoing complications and progression of ventricular remodeling. Risk stratification plays a crucial role in determining the optimal timing for surgery and tailoring treatment plans. Various clinical factors, imaging assessments, scoring systems, biomarkers, and hemodynamic parameters aid in risk assessment and guide decision-making. Pharmacological interventions, including vasopressors, diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, antiplatelet agents, and antiarrhythmic drugs, are employed to stabilize hemodynamics, prevent complications, promote myocardial healing, and improve outcomes in VSR patients. Advancements in minimally invasive techniques, such as percutaneous device closure, and tissue engineering hold promise for less invasive interventions and better outcomes. These approaches aim to minimize surgical morbidity, optimize healing, and enhance patient recovery. In conclusion, the management of VSR after MI requires a multidimensional approach that considers various aspects, including risk stratification, surgical timing, pharmacological interventions, minimally invasive techniques, and tissue engineering.

Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis.

The aim of this study was to compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide in patients with hypertension. The present meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search for relevant articles was conducted on PubMed, Scopus, and CINAHIL databases from their inception until March 31, 2023. Keywords used to search for relevant articles included "hydrochlorothiazide," "chlortalidone," "hypertension," "cardiovascular," and "blood pressure." The outcomes assessed in this meta-analysis included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Myocardial infarction, stroke, and all-cause mortality were also assessed. For safety analysis, we evaluated the risk of hypokalemia between the two groups. Any disagreement between the two authors in the data extraction process was resolved through discussion. Eight studies fulfilled the inclusion criteria included in the present meta-analysis. Our analysis showed that chlorthalidone was superior to hydrochlorothiazide in controlling both SBP and DBP, with no significant heterogeneity reported. However, there was no significant difference between the two groups in terms of the risk of myocardial infarction, stroke, all-cause mortality, and hospitalization due to heart failure. The hypokalemia rate was reported to be higher with chlorthalidone compared to hydrochlorothiazide.

Association of Deja vu With Cardiovascular Diseases.

Recent studies have suggested a link between déjà vu and cardiovascular diseases (CVDs). While the mechanism for this association is not fully understood, 1 theory suggests that déjà vu may be a result of a disruption in the temporal lobe, which is also responsible for regulating blood pressure and heart rate. Another theory suggests that there may be a shared genetic factor between the 2 conditions, with certain individuals being predisposed to experiencing both. The Apolipoprotein E (APOE) gene, in particular, has been associated with memory processing, Alzheimer's disease, and an increased risk of CVD. The protein encoded by this gene is involved in the metabolism of lipoproteins, including cholesterol and triglycerides, and is also involved in the development of atherosclerosis, which is a key risk factor for CVD. Several hypotheses have been proposed to explain how the APOE4 isoform contributes to CVD, including impairing the clearance of lipoproteins, promoting inflammation, and causing endothelial dysfunction. Psychological factors such as stress may also contribute to the development of CVD, and déjà vu may be associated with emotional arousal and stress. Further research is needed to fully understand the link between déjà vu and CVDs and to explore potential treatment options for individuals who experience both conditions.

Impacts of lockdown on the dynamics of forestry biomass, wildlife species and control of atmospheric pollution.

In this paper, we have formulated and analysed a mathematical model to investigate the impacts of lockdown on the dynamics of forestry biomass, wildlife species and pollution. For this purpose, we have considered a nonlinear system of four ordinary differential equations representing rates of change of the density of forestry biomass, the density of wildlife species, the concentration of pollutants and lockdown. Conditions for the existence, uniqueness and local stability of all equilibria along with the global stability of the interior equilibrium point are derived. Furthermore, conditions that influence the persistence of the system are obtained. By formulating an optimal control problem, the optimal strategies for minimizing the cost of implementation of lockdown as well as the concentration of pollutants are also studied. Numerical simulations are carried out to verify and validate our analytical findings. By this study, we have observed that implementation of lockdown for a sufficient period of time minimizes excessive harvesting of both forestry biomass and wildlife species and the concentration of pollutants in the environment. It is also found that lockdown policy is effective in the optimal control of atmospheric pollution. Therefore, lockdown plays a significant role in the dynamics of forestry biomass, wildlife species and control of pollution in the environment.

Investigating the plant growth promoting and biocontrol potentiality of endophytic Streptomyces SP. SP5 against early blight in Solanum lycopersicum seedlings.

BACKGROUND: Early blight (EB), caused by Alternaria solani, is one of the alarming diseases that restrict tomato production globally. Existing cultural practices and fungicide applications are not enough to control early blight diseases. Therefore, the study aimed to isolate, identify, and characterize an endophytic Streptomyces exhibiting the potential to control early blight in tomato and also promote plant growth. RESULTS: From a Citrus jambhiri leaf, an endophytic Streptomyces sp. with antagonistic activity against Alternaria solani, Colletotrichum acutatum, Cladosporium herbarum, Alternaria brassicicola, Alternaria sp., Fusarium oxysporum and Fusarium sp. was isolated. It was identified as a Streptomyces sp. through 16S ribosomal DNA sequence analysis and designated as SP5. It also produced indole acetic acid which was confirmed by Salkowski reagent assay, TLC and HPLC analysis. Treatment of pathogen infected plants with Streptomyces sp. SP5 antagonists (culture cells/culture supernatant/solvent extract/ acetone precipitates) decreased the early blight disease incidence and significantly increased the various agronomic traits. CONCLUSION: The present study concluded that Streptomyces sp. SP5 possessed antifungal activity against different fungal phytopathogens and had significant potential to control early blight disease and promote plant growth.

Transfusion-Related Renal Dysfunction After Cardiac Surgery: The Role of Myeloid-Related Protein_14 in Neutrophil-Mediated Tubular Damage.

Transfusion is a specific cause of acute kidney injury (AKI) after cardiac surgery. Whether there is an association between the composition of blood products and the onset of AKI is unknown. The present study suggests that the transfusion of packed red blood cells containing a high amount of myeloid-related protein 14 (MRP_14) could increase the incidence of AKI after cardiac surgery. In a mouse model, MRP_14 increased the influx of neutrophils in the kidney after ischemia-reperfusion and their ability to damage tubular cells. Higher concentrations of MRP_14 were found in packed red blood cells from female donors or prepared by whole blood filtration.

Runx3 drives a CD8+ T cell tissue residency program that is absent in CD4+ T cells.

Tissue-resident memory T cells (TRM cells) provide rapid and superior control of localized infections. While the transcription factor Runx3 is a critical regulator of CD8+ T cell tissue residency, its expression is repressed in CD4+ T cells. Here, we show that, as a direct consequence of this Runx3-deficiency, CD4+ TRM cells lacked the transforming growth factor (TGF)-ß-responsive transcriptional network that underpins the tissue residency of epithelial CD8+ TRM cells. While CD4+ TRM cell formation required Runx1, this, along with the modest expression of Runx3 in CD4+ TRM cells, was insufficient to engage the TGF-ß-driven residency program. Ectopic expression of Runx3 in CD4+ T cells incited this TGF-ß-transcriptional network to promote prolonged survival, decreased tissue egress, a microanatomical redistribution towards epithelial layers and enhanced effector functionality. Thus, our results reveal distinct programming of tissue residency in CD8+ and CD4+ TRM cell subsets that is attributable to divergent Runx3 activity.

Corneal tissue-resident memory T cells form a unique immune compartment at the ocular surface.

The eye is considered immune privileged such that immune responses are dampened to protect vision. As the most anterior compartment of the eye, the cornea is exposed to pathogens and can mount immune responses that recruit effector T cells. However, presence of immune memory in the cornea is not defined. Here, we use intravital 2-photon microscopy to examine T cell responses in the cornea in mice. We show that recruitment of CD8+ T cells in response to ocular virus infection results in the formation of tissue-resident memory T (TRM) cells. Motile corneal TRM cells patrol the cornea and rapidly respond in situ to antigen rechallenge. CD103+ TRM cell generation requires antigen and transforming growth factor ß. In vivo imaging in humans also reveals highly motile cells that patrol the healthy cornea. Our study finds that TRM cells form in the cornea where they can provide local protective immunity.

Differential location of NKT and MAIT cells within lymphoid tissue.

Natural Killer T (NKT) cells and Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells that express semi-invariant αß T cell receptors (TCRs) through which they recognise CD1d and MR1 molecules, respectively, in complex with specific ligands. These cells play important roles in health and disease in many organs, but their precise intra-organ location is not well established. Here, using CD1d and MR1 tetramer staining techniques, we describe the precise location of NKT and MAIT cells in lymphoid and peripheral organs. Within the thymus, NKT cells were concentrated in the medullary side of the corticomedullary junction. In spleen and lymph nodes, NKT cells were mainly localised within T cell zones, although following in vivo activation with the potent NKT-cell ligand α-GalCer, they expanded throughout the spleen. MAIT cells were clearly detectable in Vα19 TCR transgenic mice and were rare but detectable in lymphoid tissue of non-transgenic mice. In contrast to NKT cells, MAIT cells were more closely associated with the B cell zone and red pulp of the spleen. Accordingly, we have provided an extensive analysis of the in situ localisation of NKT and MAIT cells and suggest differences between the intra-organ location of these two cell types.

A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity.

The spleen is a compartmentalized organ that serves as a blood filter and safeguard of systemic immune surveillance. Labyrinthine networks of fibroblastic stromal cells construct complex niches within the white pulp and red pulp that are important for tissue homeostasis and immune activation. However, the identity and roles of the global splenic fibroblastic stromal cells in homeostasis and immune responses are poorly defined. Here, we performed a cellular and molecular dissection of the splenic reticular stromal cell landscape. We found that white pulp fibroblastic reticular cells (FRCs) responded robustly during acute viral infection, but this program of gene regulation was suppressed during persistent viral infection. Single-cell transcriptomic analyses in mice revealed diverse fibroblast cell niches and unexpected heterogeneity among podoplanin-expressing cells that include glial, mesothelial, and adventitial cells in addition to FRCs. We found analogous fibroblastic stromal cell diversity in the human spleen. In addition, we identify the transcription factor SpiB as a critical regulator required to support white pulp FRC differentiation, homeostatic chemokine expression, and antiviral T cell responses. Together, our study provides a comprehensive map of fibroblastic stromal cell types in the spleen and defines roles for red and white pulp fibroblasts for splenic function and orchestration of immune responses.

Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes.

Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-ß signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes.

Modelling and analysis of a SEIQR model on COVID-19 pandemic with delay.

This paper deals with mathematical modelling and analysis of a SEIQR model to study the dynamics of COVID-19 considering delay in conversion of exposed population to the infected population. The model is analysed for local and global stability using Lyapunov method of stability followed by Hopf bifurcation analysis. Basic reproduction number is determined, and it is observed that local and global stability conditions are dependent on the number of secondary infections due to exposed as well as infected population. Our study reveals that asymptomatic cases due to exposed population play a vital role in increasing the COVID-19 infection among the population.

Aptamer-based diagnostic and therapeutic approaches in animals: Current potential and challenges.

Fast and precise diagnosis of infectious and non-infectious animal diseases and their targeted treatments are of utmost importance for their clinical management. The existing biochemical, serological and molecular methods of disease diagnosis need improvement in their specificity, sensitivity and cost and, are generally not amenable for being used as points-of-care (POC) device. Further, with dramatic changes in environment and farm management practices, one should also arm ourselves and prepare for emerging and re-emerging animal diseases such as cancer, prion diseases, COVID-19, influenza etc. Aptamer - oligonucleotide or short peptides that can specifically bind to target molecules - have increasingly become popular in developing biosensors for sensitive detection of analytes, pathogens (bacteria, virus, fungus, prions), drug residues, toxins and, cancerous cells. They have also been proven successful in the cellular delivery of drugs and targeted therapy of infectious diseases and physiological disorders. However, the in vivo application of aptamer-mediated biosensing and therapy in animals has been limited. This paper reviews the existing reports on the application of aptamer-based biosensors and targeted therapy in animals. It also dissects the various modifications to aptamers that were found to be successful in in vivo application of the aptamers in diagnostics and therapeutics. Finally, it also highlights major challenges and future directions in the application of aptamers in the field of veterinary medicine.

CD8+ and CD4+ T Cells Infiltrate into the Brain during Plasmodium berghei ANKA Infection and Form Long-Term Resident Memory.

In the Plasmodium berghei ANKA mouse model of malaria, accumulation of CD8+ T cells and infected RBCs in the brain promotes the development of experimental cerebral malaria (ECM). In this study, we used malaria-specific transgenic CD4+ and CD8+ T cells to track evolution of T cell immunity during the acute and memory phases of P. berghei ANKA infection. Using a combination of techniques, including intravital multiphoton and confocal microscopy and flow cytometric analysis, we showed that, shortly before onset of ECM, both CD4+ and CD8+ T cell populations exit the spleen and begin infiltrating the brain blood vessels. Although dominated by CD8+ T cells, a proportion of both T cell subsets enter the brain parenchyma, where they are largely associated with blood vessels. Intravital imaging shows these cells moving freely within the brain parenchyma. Near the onset of ECM, leakage of RBCs into areas of the brain can be seen, implicating severe damage. If mice are cured before ECM onset, brain infiltration by T cells still occurs, but ECM is prevented, allowing development of long-term resident memory T cell populations within the brain. This study shows that infiltration of malaria-specific T cells into the brain parenchyma is associated with cerebral immunopathology and the formation of brain-resident memory T cells. The consequences of these resident memory populations is unclear but raises concerns about pathology upon secondary infection.