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Subarachnoid hemorrhage (SAH) can be associated with neurological deficits and has profound consequences for mortality and morbidity. Cerebral vasospasm (CVS) and delayed cerebral ischemia affect neurological outcomes in SAH patients, but their mechanisms are not fully understood, and effective treatments are limited. Here, we report that urotensin II receptor UT plays a pivotal role in both early events and delayed mechanisms following SAH in male mice. Few days post-SAH, UT expression is triggered by blood or hemoglobin in the leptomeningeal compartment. UT contributes to perimeningeal glia limitans astrocyte reactivity, microvascular alterations and neuroinflammation independent of CNS-associated macrophages (CAMs). Later, CAM-dependent vascular inflammation and subsequent CVS develop, leading to cognitive dysfunction. In an SAH model using humanized UT h+ / h+ male mice, we show that post-SAH CVS and behavioral deficits, mediated by UT through Gq/PLC/Ca 2+ signaling, are prevented by UT antagonists. These results highlight the potential of targeting UT pathways to reduce early meningeal response and delayed cerebral ischemia in SAH patients., (© 2024. The Author(s).)

Long considered to fluctuate between pro- and anti-inflammatory states, it has now become evident that microglia occupy a variegated phenotypic landscape with relevance to aging and neurodegeneration. However, whether specific microglial subsets converge in or contribute to both processes that eventually affect brain function is less clear. To investigate this, we analyzed microglial heterogeneity in a tauopathy mouse model (K18-seeded P301L) and an accelerated aging model (Senescence-Accelerated Mouse-Prone 8, SAMP8) using cellular indexing of transcriptomes and epitopes by sequencing. We found that widespread tau pathology in K18-seeded P301L mice caused a significant change in the number and morphology of microglia, but only a mild overrepresentation of disease-associated microglia. At the cell population-level, we observed a marked upregulation of the calprotectin-encoding genes S100a8 and S100a9. In 9-month-old SAMP8 mice, we identified a unique microglial subpopulation that showed partial similarity with the disease-associated microglia phenotype and was additionally characterized by a high expression of the same calprotectin gene set. Immunostaining for S100A8 revealed that this population was enriched in the hippocampus, correlating with the cognitive impairment observed in this model. However, incomplete colocalization between their residence and markers of neuronal loss suggests regional specificity. Importantly, S100A8-positive microglia were also retrieved in brain biopsies of human AD and tauopathy patients as well as in a biopsy of an aged individual without reported pathology. Thus, the emergence of S100A8-positive microglia portrays a conspicuous commonality between accelerated aging and tauopathy progression, which may have relevance for ensuing brain dysfunction., (© 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Purpose: Segmental resection is recommended for malignant polyps of the colon that are removed endoscopically with questionable margins. However, when such a lesion is present in the rectum, radical resection may involve a higher risk procedure such as low anterior resection or abdominoperineal resection. We report our long-term results in patients treated by transanal re-excision (TAR) following endoscopic removal of malignant rectal polyps (MRP)., Methods: Twenty-three patients were identified between 2000 and 2006 as having undergone TAR following complete gross endoscopic removal of an MRP. All lesions demonstrated close, unclear, or microscopically positive polypectomy margins., Results: Our population consisted of 13 men and 10 women with a median age of 61 years (range 52-86). Seventeen (74%) patients demonstrated no evidence of residual tumor. Six patients were found to have residual disease (three adenoma, two adenocarcinoma, one positive lymph node). Morbidity was minimal, and there were no mortalities. At a median follow-up of 64.6 months (range 11-90), there have been no recurrences., Conclusion: We conclude that in approximately one quarter of patients, residual disease is identified following TAR. Given the relatively safety and the low recurrence rate associated with this procedure, TAR may be considered as an alternative to radical resection for MRPs with unsatisfactory margins.