Imiquimod Reverses Chronic Toxoplasmosis-Associated Behavioral and Neurocognitive Anomalies in a Rat Model.

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. Toxoplasma gondii (T. gondii) transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening. Behavioral and neurological complications have been associated with CT. Furthermore, an effective treatment targeting CT is still lacking. We previously reported the efficacy of imiquimod against CT. Here, we demonstrate the molecular effects of imiquimod or imiquimod followed by the clinically used combination of sulfadiazine and pyrimethamine (SDZ + PYR) on CT-associated behavior in a rat model. Imiquimod decreased the number of cysts in the brains of chronically infected rats due to an induced reactivation of bradyzoites into tachyzoites. Importantly, this decrease was more pronounced in rats treated with imiquimod followed by SDZ + PYR. Rats chronically infected with T. gondii exhibited an anxiety-like behavior. Notably, treatment with imiquimod reversed this behavior aberrancy, with even a more pronounced effect with imiquimod followed by SDZ/PYR. Similarly, rats chronically infected with T. gondii exhibited learning deficits, and imiquimod alone or followed by SDZ/PYR reversed this behavior. Our results enhance our knowledge of the implications of CT on behavioral aberrancies and highlight the potency of imiquimod followed by SDZ + PYR on these CT-associated complications.

Inflammasomes as biomarkers and therapeutic targets in traumatic brain injury and related-neurodegenerative diseases: A comprehensive overview.

Given the ambiguity surrounding traumatic brain injury (TBI) pathophysiology and the lack of any Food and Drug Administration (FDA)-approved neurotherapeutic drugs, there is an increasing need to better understand the mechanisms of TBI. Recently, the roles of inflammasomes have been highlighted as both potential therapeutic targets and diagnostic markers in different neurodegenerative disorders. Indeed, inflammasome activation plays a pivotal function in the central nervous system (CNS) response to many neurological conditions, as well as to several neurodegenerative disorders, specifically, TBI. This comprehensive review summarizes and critically discusses the mechanisms that govern the activation and assembly of inflammasome complexes and the major methods used to study inflammasome activation in TBI and its implication for other neurodegenerative disorders. Also, we will review how inflammasome activation is critical in CNS homeostasis and pathogenesis, and how it can impact chronic TBI sequalae and increase the risk of developing neurodegenerative diseases. Additionally, we discuss the recent updates on inflammasome-related biomarkers and the potential to utilize inflammasomes as putative therapeutic targets that hold the potential to better diagnose and treat subjects with TBI.

The relationship between clinical insight and cognitive and affective empathy in schizophrenia.

BACKGROUND: Schizophrenia is often associated with poor clinical insight (unawareness of mental illness and its symptoms) and deficits in empathy, which are important for social functioning. Cognitive empathy has been linked to clinical insight while affective empathy and its role in insight and pathology have received mixed evidence. METHODS: Instruments assessing symptomatology (Positive and Negative Syndrome Scale; PANSS), clinical insight (Scales to assess awareness of mental disorders; SUMD), and cognitive and affective empathy were administered to 22 participants with first episode and chronic schizophrenia and 21 healthy controls. Self-report, parent-report, and performance based measures were used to assess cognitive and affective empathy (The interpersonal reactivity index; IRI/Reading the Mind in the Eyes Test/Faux Pas) to reduce bias and parse shared variance. RESULTS: Age of onset, gender, and symptomatology emerged as significant predictors of poor clinical insight. Additionally, the fantasy subscale of the IRI as reported by parents emerged as a positive predictor while the personal distress (parent report) subscale emerged as a negative predictor of awareness into mental illness. There were significant differences on performance-based measures of empathy between the control and schizophrenia groups. CONCLUSION: Findings suggest that affective empathy is relatively intact across phases of illness whereas cognitive empathy abilities are compromised and could be targets for psychotherapy intervention.