Browsing by Author "Mason, Matthew"

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    Malignant lymphomatous invasion of Meckel’s cave: pathoanatomical considerations of the petrous apex
    (BMJ Publishing, 2021-11-11) Marotta, Dario Alfredo; Mason, Matthew; Cohen-Gadol, Aaron; Kesserwani, Hassan; Neurological Surgery, School of Medicine
    Secondary central nervous system lymphoma is rare, occurring in up to 10% of non-Hodgkin's lymphoma patients and in 5% of diffuse large B-cell lymphoma patients. The prognosis is poor, even rarer is metastasis of large B-cell lymphomas into Meckel’s cave and the trigeminal nerve roots. We describe a relapsing case of a large B-cell lymphoma that migrated into Meckel’s cave, the mandibular branch of the trigeminal nerve and the adjacent cavernous sinus. We review petrous apex anatomy, review the literature of metastatic spread into Meckel’s cave and analyse existing pathoanatomical studies that explain the conduits and barriers of tumour spread. Understanding this pathoanatomical relationship is critical for neurologists and neurosurgeons alike to effectively correlate patient signs and symptoms to intracranial pathology and identify origins and sites of metastatic dispersion in similar rare clinical scenarios.
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    Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates
    (American Association for the Advancement of Science, 2021) Brelstaff, Jack H.; Mason, Matthew; Katsinelos, Taxiarchis; McEwan, William A.; Ghetti, Bernardino; Tolkovsky, Aviva M.; Grazia Spillantini, Maria; Pathology and Laboratory Medicine, School of Medicine
    The microtubule-associated protein tau aggregates in multiple neurodegenerative diseases, causing inflammation and changing the inflammatory signature of microglia by unknown mechanisms. We have shown that microglia phagocytose live neurons containing tau aggregates cultured from P301S tau mice due to neuronal tau aggregate-induced exposure of the “eat me” signal phosphatidylserine. Here, we show that after phagocytosing tau aggregate-bearing neurons, microglia become hypophagocytic while releasing seed-competent insoluble tau aggregates. These microglia express a senescence-like phenotype, demonstrated by acidic β-galactosidase activity, secretion of paracrine senescence-associated cytokines, and maturation of matrix remodeling enzymes, results that are corroborated in P301S mouse brains and ex vivo brain slices. In particular, the nuclear factor κB–dependent activation of matrix metalloprotease 3 (MMP3/stromelysin1) was replicated in brains from patients with tauopathy. These data show that microglia that have been activated to ingest live tau aggregates-bearing neurons behave hormetically, becoming hypofunctional while acting as vectors of tau aggregate spreading.