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Private Protection at the Brain's Border News & views flood extents and population exposure3,4. They and nature-based approaches might be e-mail: [email protected] found that the number of people exposed insufficient to deal with rising sea levels — the 1. van Loenhout, J. et al. Human Cost of Disasters to floods is likely to continue to increase only option for some communities will be to 2000–2019 (CRED/UNDRR, 2020). more quickly than the overall population in manage their retreat out of flood-prone areas11. 2. Tellman, B. et al. Nature 596, 80–86 (2021). 59 countries, mostly in Asia and Africa. Understanding the links between climate 3. World Resources Institute. Aqueduct Global Flood Risk Maps (2015). Previous studies in this area relied on global change, socio-economic development 4. Winsemius, H. C. et al. Nature Clim. Change 6, 381–385 flood models that use rainfall statistics and and flooding is a big scientific challenge, (2015). elevation models to map potential river- but is essential for developing robust deci- 5. Ward, P. J. et al. Nature Clim. Change 5, 712–715 (2015). 5 6. Browder, G. et al. An EPIC Response: Innovative ine and coastal flood zones . Tellman et al. sion-support models that will enable policy- Governance for Flood and Drought Risk Management instead mapped an unprecedented number makers to calculate and communicate the best (World Bank, 2021). of validated events, including various flood mix of measures for future challenges. Tellman 7. Jongman, B. et al. Proc. Natl Acad. Sci. USA 112, E2271–E2280 (2015). types — such as those caused by dam breaks, and colleagues’ improved global estimates of 8. Girardin, C. A. J. et al. Nature 593, 191–194 (2021). local rainfall events and snowmelt — that had risk are a crucial step in that direction. 9. Sudmeier-Rieux, K. et al. Nature Sustain. https://doi. not been considered in the earlier analyses. As org/10.1038/s41893-021-00732-4 (2021). 10. Crowther, T. W. et al. Nature 525, 201–205 (2015). a result, the authors’ estimate of the increase Brenden Jongman is at the Global Facility for 11. Haasnoot, M., Lawrence, J. & Magnan, A. K. Science 372, in the percentage of people exposed to floods Disaster Reduction and Recovery, World Bank, 1287–1290 (2021). globally is ten times higher than previous Washington DC 20433, USA. The author declares no competing interests. estimates. As with all global assessments, the new work Immunology has its limitations. The flood events consid- ered are still just a subset of all the floods that occurred during the study period. This is because the satellite observations capture Private protection at only floods above a certain spatial extent and that were followed by a period of cloud-free the brain’s border weather, thereby allowing reliable optical detection. Furthermore, the spatial resolution Britta Engelhardt of the satellite data and the use of global popu- lation models do not allow a detailed analysis At the outer border of the brain and spinal cord, immune cells of flood impact in urban areas. Given that the have been observed that originate from the bone marrow of world is rapidly urbanizing and that urban disaster risk is an increasing concern, future the adjacent skull and vertebrae. They reach this site through studies should develop improved approaches special bone channels, without passing through the blood. for estimating global flood risk in cities. The trends revealed in Tellman and col- leagues’ study might seem daunting, but Barriers around the brain and spinal cord of The pia mater lies directly on top of the glia there is also good news to be drawn from the the central nervous system (CNS) protect limitans, a thin layer of extracellular-matrix statistics: the capacity of communities to man- neuronal cells from the changeable milieu of mater ial and cell-protrusion endings at the age and respond to floods has increased over the bloodstream by controlling movement of surface of the CNS tissue4. The anatomy of time. Investments in flood protection, drain- molecules and cells between the blood and the meningeal layers has been likened to age infrastructure and early-warning systems, the CNS. These barriers also ensure that the the defences around a medieval castle, with together with improved building standards, CNS can be kept under surveillance by cer- two walls (the arachnoid barrier and the glia schemes for supporting flood-affected people tain immune cells, but restrict the access of limitans) bordering a guard-patrolled moat and strengthened government policies enforc- blood-derived immune cells and molecules (the subarachnoid space and its immune ing risk-informed land planning, can both pre- to specific compartments at the border of the cells)6. vent floods and buffer the impacts when they CNS1. Writing in Science, Cugurra et al.2 and The two new studies focused on different occur6. The number of fatalities and extent of Brioschi et al.3 report that the dura mater, a subsets of immune cells, namely, myeloid cells flood damage, relative to the number of people tissue layer around the outermost barrier of of the innate branch of the immune system and economic assets exposed to floods, has the CNS, sources a private immune protection (which recognizes stereotypical changes declined globally over the past few decades7. from nearby bone marrow. characteristic of infection)2 and B cells of the As the global population grows and cities Encasing the brain and the spinal cord adaptive immune system (which responds expand, natural ecosystems that once pro- are three meningeal membranes1,4 (Fig. 1). to and remembers specific foreign invad- vided flood protection will also be under The outermost membrane, the dura mater, ers)3. The authors attached the circulatory threat. Mangroves, coral reefs, dune systems lacks a blood–brain barrier, and so the entry system of one mouse, in which these subsets and urban parks can damp flood waves, reduce of blood-derived components, including of immune cells were fluorescently tagged, peak flows and significantly reduce flooding immune cells, into this layer is unrestricted1,4. to that of a second, untreated, mouse, and and other climate-related hazards8. Invest- The arachnoid mater is attached to the inner made the surprising finding that fewer tagged ments in solutions that restore or construct surface of the dura mater. Between the cells than untagged cells were observed in the ecosystems often provide a cost-effective way arachnoid mater and the innermost meningeal dura mater of the second mouse. This finding of reducing flood damage while improving bio- layer, the pia mater, is the subarachnoid space, suggests that a considerable proportion of diversity and providing other benefits9. Satel- which contains cerebrospinal fluid (CSF) immune cells in the dura mater do not arrive lite technology can track changes in protective and resident immune cells that enter during from the bloodstream, but instead originate ecosystems10, similarly to its use in monitoring embryonic development5. The arachnoid from the bone marrow in the skull and the flooding and population changes. However, mater acts as a blood–CSF barrier between vertebrae of the spine. This shortcut is made even the best combination of infrastructure the dura mater and the subarachnoid space. possible by the cells crawling along the outside 38 | Nature | Vol 596 | 5 August 2021 ©2021 Spri nger Nature Li mited. All rights reserved. ©2021 Spri nger Nature Li mited. All rights reserved. of blood vessels inside small, bony channels, identified previously7, between the bone Skull bone Bone-marrow-derived marrow and the dura mater (Fig. 1). Thus, the immune cell dura mater sources a private immune protec- tion right outside the outer CNS barrier (the arachnoid mater) from adjacent bone marrow through a previously unrecognized route. Analysis of gene expression and other Channel characteristics of the individual dura mater containing Blood-derived blood vessel immune cells supported the idea that these immune cell bone-marrow-derived immune cells are pro- Dura mater grammed to ensure CNS health, whereas those arriving from the blood tend to be pro-inflammatory and thus more ready to fight Arachnoid mater potential infections. Moreover, with ageing, Resident increasing numbers of blood-derived immune Subarachnoid Pia subarachnoid immune cell cells were observed in the dura mater, suggest- space (CSF) mater ing a shift in CNS-border immune protection. Unexpectedly, Cugurra et al.2 found a large Brain Glia limitans number of a type of bone-marrow-derived immune cell called granulocytes in the dura Figure 1 | Immune cells from the bone marrow outside the border of the central nervous system mater. Granulocytes are not typically resi- (CNS). Cugurra et al.2 and Brioschi et al.3 studied immune cells in the dura mater, the outermost of three dent in tissue: they are short-lived, circulate meningeal membranes that surround the brain and spinal cord. In addition to immune cells derived from the in the blood and usually infiltrate tissue only bloodstream, they observed immune cells in the dura mater that originated directly from the neighbouring during acute inflammation. However, the bone marrow in the skull or vertebrae. Immune cells from the bone marrow enter the dura mater by moving authors found these cells in the apparently along the outside of blood vessels in channels in the bone. The other two meningeal membranes — the arachnoid mater and pia mater — surround the subarachnoid space, which contains cerebrospinal fluid uninflamed dura mater, and, indeed, granulo- (CSF) and its own immune cells that enter during embryonic development. The arachnoid mater establishes cytes have been observed in healthy meninges a cellular barrier between the dura mater and the CNS. Under the pia mater, the glia limitans layer, which is previously6. made of extracellular matrix material and cellular processes, establishes a further barrier.
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