Preprints

2022

1. bioarXiv

   Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis

   Pulous, F. E., Cruz-Hernandez, J. C., Yang, C. B., Kaya, Z., Paccalet, A., Wojtkiewicz, G., Capen, D., Brown, D., Wu, J. W., Schloss, M. J., Vinegoni, C., Richter, D., Yamazoe, M., Hulsmans, M., Momin, N., Grune, J., Rohde, D., McAlpine, C. S., Panizzi, P., Weissleder, R., Kim, D. E., Swirski, F. K., Lin, C. P., Moskowitz, M. A., and Nahrendorf, M.

   bioarXiv preprint bioarXiv:10.1101/2021.08.27.457954v1 2022

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   Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues facilitate intersystem communication. Cerebrospinal fluid (CSF), which interfaces with the glymphatic system and thereby drains the brain’s interstitial and perivascular spaces, facilitates outward signaling beyond the blood-brain barrier. In the present study, we report that CSF can exit into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice migrate along perivascular spaces of dural blood vessels and then travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria hijack this route to invade the skull’s hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. As skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in CSF by regional marrow may have broad implications for inflammatory neurological disorders. This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow.

   @article{2022-NN,
     author = {Pulous, F. E. and Cruz-Hernandez, J. C. and Yang, C. B. and Kaya, Z. and Paccalet, A. and Wojtkiewicz, G. and Capen, D. and Brown, D. and Wu, J. W. and Schloss, M. J. and Vinegoni, C. and Richter, D. and Yamazoe, M. and Hulsmans, M. and Momin, N. and Grune, J. and Rohde, D. and McAlpine, C. S. and Panizzi, P. and Weissleder, R. and Kim, D. E. and Swirski, F. K. and Lin, C. P. and Moskowitz, M. A. and Nahrendorf, M.},
     title = {Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis},
     journal = {bioarXiv preprint bioarXiv:10.1101/2021.08.27.457954v1},
     alternatejournal = {bioarXiv},
     year = {2022},
     volume = {25},
     number = {5},
     pages = {567-+},
     pdf = {2022-NN.pdf},
     abbr = {bioarXiv},
     html = {2022-NN},
     bibtex_show = {true}
   }
2. Nat. Card. Res.

   Neutrophils incite and macrophages avert electrical storm after myocardial infarction

   Grune, J., Lewis, A.J.M., Yamazoe, M., Hulsmans, M., Rohde, D., Xiao, L., Zhang, S., Ott, C., Calcagno, D.M., Zhou, Y., Timm, K., Shanmuganathan, M., Pulous, F.E., Schloss, M.J., Foy, B.H., Capen, D., Vinegoni, C., Wojtkiewicz, G.R., Iwamoto, I., Grune, T., Brown, D., Higgins, J., Ferreira, V.M., Herring, N., Channon, K.M., Neubauer, S., Study, Oxford Acute Myocardial Infarction (OxAMI), Sosnovik, D.E., Milan, D.J., Swirski, F.K., King, K.R., Aguirre, A.D., Ellinor, P.T., and Nahrendorf^#, M.

   Nature Cardiovascular Research 2022

   ABS DOI CITE HTML PDF

   Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2−/− mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36−/− and Mertk−/− mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death.

   @article{2022-NCR-2,
      author= {Grune, J. and Lewis, A.J.M. and Yamazoe, M. and Hulsmans, M. and Rohde, D. and Xiao, L. and Zhang, S. and Ott, C. and Calcagno, D.M. and Zhou, Y. and Timm, K. and Shanmuganathan, M. and Pulous, F.E. and Schloss, M.J. and Foy, B.H. and Capen, D. and Vinegoni, C. and Wojtkiewicz, G.R. and Iwamoto, I. and Grune, T. and Brown, D. and Higgins, J. and Ferreira, V.M. and Herring, N. and Channon, K.M. and Neubauer, S. and Oxford Acute Myocardial Infarction (OxAMI) Study and Sosnovik, D.E. and Milan, D.J. and Swirski, F.K. and King, K.R. and Aguirre, A.D. and Ellinor, P.T. and Nahrendorf, M.},
      title = {Neutrophils incite and macrophages avert electrical storm after myocardial infarction},
      journal = {Nature Cardiovascular Research},
      alternatejournal = {Nat. Card.  Res.},
      year = {2022},
      volume = {1},
      number = {1},
      pages = {649–664},
      doi = {10.1038/s44161-022-00094-w},
   }

   10.1038/s44161-022-00094-w