P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice.

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: Sepsis was induced in wild-type (WT), P2X7-/-, and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7-/- sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba-1) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7-/- sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1ß (IL-1ß), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target.

Sensory and muscular functions of the pelvic floor in women with endometriosis - cross-sectional study.

PURPOSE: The aim of this study was to analyze the sensory and muscle functions of the pelvic floor in women with endometriosis, trying to improve overall knowledge/findings regarding pelvic floor muscle functions in patients with endometriosis. METHODS: Sample size calculated as 92 patients with endometriosis, aged between 18 and 45 years, not virgin, without other causes of pain and could not be pregnant. Patients underwent the Pelvic Floor Sensorial and Muscle Function Exam (EFSMAP). Descriptive data were recorded with mean and standard deviation, median (range), and absolute and relative frequency. The Kolmogorov-Smirnov test was used to observe the normality of quantitative variables. The significance level adopted for this study was 5%. RESULTS: Of 92 women assessed, 93.3% had pain and 75% had increased tone in the levator ani muscle; 50.4% had impaired pelvic floor relaxation with median strength of 3 by the Oxford scale and endurance of 2 s. CONCLUSIONS: The patients had a high prevalence of pain and dysfunction of the pelvic floor muscles, such as low muscle endurance and difficulty to relax. It shows that these patients should be referred to a pelvic floor physiotherapist, as soon as they have the diagnosis of endometriosis, to be assessed to prevent and/or treat pelvic floor impairments.