Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

EASD 2024

Keep up to date with the top stories from the 60th EASD Annual Meeting with our congress hub page.
ADVANCED SEARCH
Log in
Top
Fluids and Barriers of the CNS
Published in:

Open Access 01-12-2023 | Hydrocephalus | Research

Early postnatal microglial ablation in the Ccdc39 mouse model reveals adverse effects on brain development and in neonatal hydrocephalus

Authors: Farrah N. Brown, Eri Iwasawa, Crystal Shula, Elizabeth M. Fugate, Diana M. Lindquist, Francesco T. Mangano, June Goto

Published in: Fluids and Barriers of the CNS | Issue 1/2023

Login to get access

Abstract

Background

Neonatal hydrocephalus is a congenital abnormality resulting in an inflammatory response and microglial cell activation both clinically and in animal models. Previously, we reported a mutation in a motile cilia gene, Ccdc39 that develops neonatal progressive hydrocephalus (prh) with inflammatory microglia. We discovered significantly increased amoeboid-shaped activated microglia in periventricular white matter edema, reduced mature homeostatic microglia in grey matter, and reduced myelination in the prh model. Recently, the role of microglia in animal models of adult brain disorders was examined using cell type-specific ablation by colony-stimulating factor-1 receptor (CSF1R) inhibitor, however, little information exists regarding the role of microglia in neonatal brain disorders such as hydrocephalus. Therefore, we aim to see if ablating pro-inflammatory microglia, and thus suppressing the inflammatory response, in a neonatal hydrocephalic mouse line could have beneficial effects.

Methods

In this study, Plexxikon 5622 (PLX5622), a CSF1R inhibitor, was subcutaneously administered to wild-type (WT) and prh mutant mice daily from postnatal day (P) 3 to P7. MRI-estimated brain volume was compared with untreated WT and prh mutants P7-9 and immunohistochemistry of the brain sections was performed at P8 and P18-21.

Results

PLX5622 injections successfully ablated IBA1-positive microglia in both the WT and prh mutants at P8. Of the microglia that are resistant to PLX5622 treatment, there was a higher percentage of amoeboid-shaped microglia, identified by morphology with retracted processes. In PLX-treated prh mutants, there was increased ventriculomegaly and no change in the total brain volume was observed. Also, the PLX5622 treatment significantly reduced myelination in WT mice at P8, although this was recovered after full microglia repopulation by P20. Microglia repopulation in the mutants worsened hypomyelination at P20.

Conclusions

Microglia ablation in the neonatal hydrocephalic brain does not improve white matter edema, and actually worsens ventricular enlargement and hypomyelination, suggesting critical functions of homeostatic ramified microglia to better improve brain development with neonatal hydrocephalus. Future studies with detailed examination of microglial development and status may provide a clarification of the need for microglia in neonatal brain development.
Appendix
Available only for authorised users
Literature
1.
Patel SK, Tari R, Mangano FT. Pediatric hydrocephalus and the primary care provider. Pediatr Clin North Am. 2021;68:793–809.PubMedCrossRef
2.
Paulsen AH, Lundar T, Lindegaard KF. Pediatric hydrocephalus: 40-year outcomes in 128 hydrocephalic patients treated with shunts during childhood* Assessment of surgical outcome, work participation, and health-related quality of life. J Neurosurg Pediatr. 2015;16:633–41.PubMedCrossRef
3.
Fairburn B. Choroid plexus papilloma and its relation to hydrocephalus. J Neurosurg. 1960;17:166–71.PubMedCrossRef
4.
5.
Dewan MC, Rattani A, Mekary R, Glancz LJ, Yunusa I, Baticulon RE, et al. Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg. 2018;130:1065–79.CrossRef
6.
Jeng S, Gupta N, Wrensch M, Zhao S, Wu YW. Prevalence of congenital hydrocephalus in California, 1991–2000. Pediatr Neurol. 2011;45:67–71.PubMedCrossRef
7.
Persson EK, Anderson S, Wiklund LM, Uvebrant P. Hydrocephalus in children born in 1999–2002: Epidemiology, outcome and ophthalmological findings. Child’s Nervous Syst. 2007;23:1111–8.CrossRef
8.
Pindrik J, Schulz L, Drapeau A. Diagnosis and surgical management of neonatal hydrocephalus. Semin Pediatr Neurol. 2022;78:7.
9.
Pindrik J, Riva-Cambrin J, Kulkarni AV, Alvey JS, Reeder RW, Pollack IF, et al. Surgical resource utilization after initial treatment of infant hydrocephalus: Comparing etv, early experience of etv with choroid plexus cauterization, and shunt insertion in the hydrocephalus clinical research network. J Neurosurg Pediatr. 2020;26:337–45.PubMedCrossRef
10.
del Bigio MR, Wilson MJ, Enno T. Chronic hydrocephalus in rats and humans: white matter loss and behavior changes. Ann Neurol. 2003;53:337–46.PubMedCrossRef
11.
Pattisapu Jogi V. Pattisapu 2001 Etiology and clinical course of hydro. 2001;
12.
Browd SR, Ragel BT, Gottfried ON, Kestle JRW. Failure of cerebrospinal fluid shunts: Part I: Obstruction and mechanical failure. Pediatr Neurol. 2006;89:83–92.CrossRef
13.
Yuan W, McKinstry RC, Shimony JS, Altaye M, Powell SK, Phillips JM, et al. Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus. AJNR Am J Neuroradiol. 2013;34:439–45.PubMedPubMedCentralCrossRef
14.
Patel SK, Yuan W, Mangano FT. Advanced neuroimaging techniques in pediatric hydrocephalus. Pediatr Neurosurg. 2017;7:436–45.CrossRef
15.
Miller JM, McAllister JP. Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus. Cerebrospinal Fluid Res. 2007;4:8.CrossRef
16.
Williams VJ, Juranek J, Stuebing KK, Cirino PT, Dennis M, Bowman RM, et al. Postshunt lateral ventricular volume, white matter integrity, and intellectual outcomes in spina bifida and hydrocephalus. J Neurosurg Pediatr. 2015;15:410–9.PubMedCrossRef
17.
Gadsdon DR, Variend S, Emery JL. Myelination of the corpus callosum II The effect of relief of hydrocephalus upon the processes of myelination. Z Kinderchir Grenzgeb. 1979;28:314–21.PubMed
18.
Galbreath E, Kim SJ, Park K, Brenner M, Messing A. Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus. J Neuropathol Exp Neurol. 1995;54:339–49.PubMedCrossRef
19.
Weller RO, Shulman K. Infantile hydrocephalus: clinical, histological, and ultrastructural study of brain damage. J Neurosurg. 1972;36:255–65.PubMedCrossRef
20.
del Bigio MR, Bruni JE, Fewer HD. Human neonatal hydrocephalus. An electron microscopic study of the periventricular tissue. J Neurosurg; 1985;63:56–63.
21.
22.
Iwasawa E, Brown FN, Shula C, Kahn F, Lee SH, Berta T, et al. The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model. J Neurosci. 2022;42:1820–44.PubMedPubMedCentralCrossRef
23.
Abdelhamed Z, Vuong SM, Hill L, Shula C, Timms A, Beier D, et al. A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice. Development. 2018;145:8.CrossRef
24.
Emmert AS, Iwasawa E, Shula C, Schultz P, Lindquist D, Scott Dunn R, et al. Impaired neural differentiation and glymphatic CSF flow in the Ccdc39 rat model of neonatal hydrocephalus: Genetic interaction with L1cam. DMM Disease Models and Mechanisms. 2019;12:7.
25.
Goto J, Tezuka T, Nakazawa T, Sagara H, Yamamoto T. Loss of Fyn tyrosine kinase on the C57BL/6 genetic background causes hydrocephalus with defects in oligodendrocyte development. Mol Cell Neurosci. 2008;38:203–12.PubMedCrossRef
26.
Crews L, Tony Wyss-Coray, Eliezer Masliah. Insights into the pathogenesis of hydrocephalus from transgenic and experimental animal models. Brain pathology. 2004;14:312–6.
27.
del Bigio MR, da Silva MC, Drake JM, Tuor UI. Acute and Chronic Cerebral White Matter Damage in Neonatal Hydrocephalus. Can J Neurol Sci. 1994;21:299–305.PubMedCrossRef
28.
del Bigio M, Kanfer J, Zhang Y. Myelination Delay in the cerebral white matter of immature rats. Journal of Neuropathology. 1997;56:1053–66.CrossRef
29.
McAllister JP. Pathophysiology of congenital and neonatal hydrocephalus. Semin Fetal Neonatal Med. 2012;896:285–94.CrossRef
30.
di Curzio DL, Buist RJ, del Bigio MR. Reduced subventricular zone proliferation and white matter damage in juvenile ferrets with kaolin-induced hydrocephalus. Exp Neurol. 2013;248:112–28.PubMedCrossRef
31.
Garcia-Bonilla M, Castaneyra-Ruiz L, Zwick S, Talcott M, Otun A, Isaacs AM, et al. Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter. Fluids Barriers CNS. 2022;19:723.CrossRef
32.
Aojula A, Botfield H, McAllister JP, Gonzalez AM, Abdullah O, Logan A, et al. Diffusion tensor imaging with direct cytopathological validation: Characterisation of decorin treatment in experimental juvenile communicating hydrocephalus. Fluids Barriers CNS. 2016;45:13.
33.
Lattke M, Magnutzki A, Walther P, Wirth T, Baumann B. Nuclear factor κB activation impairs ependymal ciliogenesis and links neuroinflammation to hydrocephalus formation. J Neurosci. 2012;32:11511–23.PubMedPubMedCentralCrossRef
34.
Xu H, Tan G, Zhang S, Zhu H, Liu F, Huang C, et al. Minocycline reduces reactive gliosis in the rat model of hydrocephalus. BMC Neurosci. 2012;13:23217034.CrossRef
35.
McAllister JP, Miller JM. Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus. Cerebrospinal Fluid Res. 2010;7:20507614.CrossRef
36.
Botfield H, Gonzalez AM, Abdullah O, Skjolding AD, Berry M, Mcallister JP, et al. Decorin prevents the development of juvenile communicating hydrocephalus. Brain. 2013;136:2842–58.PubMedCrossRef
37.
38.
Habiyaremye G, Morales DM, Morgan CD, McAllister JP, CreveCoeur TS, Han RH, et al. Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus. Fluids Barriers CNS. 2017;14:67.CrossRef
39.
Limbrick DD, Baksh B, Morgan CD, Habiyaremye G, McAllister JP, Inder TE, et al. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus. PLoS ONE. 2017;34:12.
40.
Schmitz ML, Weber A, Roxlau T, Gaestel M, Kracht M. Signal integration, crosstalk mechanisms and networks in the function of inflammatory cytokines. Biochim Biophys Acta. 2011;1813:2165–75.PubMedCrossRef
41.
42.
Wu KY, Tang FL, Lee D, Zhao Y, Song H, Zhu XJ, et al. Ependymal Vps35 promotes ependymal cell differentiation and survival, suppresses microglial activation, and prevents neonatal hydrocephalus. J Neurosci. 2020;40:3862–79.PubMedPubMedCentralCrossRef
43.
Dagher NN, Najafi AR, Kayala KMN, Elmore MRP, White TE, Medeiros R, et al. Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice. J Neuroinflammation. 2015;21:12.
44.
Hagemeyer N, Hanft KM, Akriditou MA, Unger N, Park ES, Stanley ER, et al. Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood. Acta Neuropathol. 2017;134:441–58.PubMedPubMedCentralCrossRef
45.
Elmore MRP, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA, et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron. 2014;82:380–97.PubMedPubMedCentralCrossRef
46.
Sawicki CM, Kim JK, Weber MD, Faw TD, McKim DB, Madalena KM, et al. Microglia promote increased pain behavior through enhanced inflammation in the spinal cord during repeated social defeat stress. J Neurosci. 2019;39:1139–49.PubMedPubMedCentralCrossRef
47.
Tang Y, Liu L, Xu D, Zhang W, Zhang Y, Zhou J, et al. Interaction between astrocytic colony stimulating factor and its receptor on microglia mediates central sensitization and behavioral hypersensitivity in chronic post ischemic pain model. Brain Behav Immun. 2018;68:248–60.PubMedCrossRef
48.
Elmore MRP, Hohsfield LA, Kramár EA, Soreq L, Lee RJ, Pham ST, et al. Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice. Aging Cell. 2018;17:7.CrossRef
49.
Rice RA, Pham J, Lee RJ, Najafi AR, West BL, Green KN. Microglial repopulation resolves inflammation and promotes brain recovery after injury. Glia. 2017;65:931–44.PubMedPubMedCentralCrossRef
50.
Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, et al. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N Engl J Med. 2015;373:428–37.PubMedCrossRef
51.
Stottmann RW, Moran JL, Turbe-Doan A, Driver E, Kelley M, Beier DR. Focusing forward genetics: A tripartite ENU screen for neurodevelopmental mutations in the mouse. Genetics. 2011;188:615–24.PubMedPubMedCentralCrossRef
52.
Goulding DS, Caleb Vogel R, Pandya CD, Shula C, Gensel JC, Mangano FT, et al. Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice. J Neurosurg Pediatr. 2020;25:476–83.CrossRef
53.
Rosin JM, Vora SR, Kurrasch DM. Depletion of embryonic microglia using the CSF1R inhibitor PLX5622 has adverse sex-specific effects on mice, including accelerated weight gain, hyperactivity and anxiolytic-like behaviour. Brain Behav Immun. 2018;73:682–97.PubMedCrossRef
54.
Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 2013;34:81–9.PubMedCrossRef
55.
Arnoux I, Hoshiko M, Mandavy L, Avignone E, Yamamoto N, Audinat E. Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory ‘Barrel’ cortex. Glia. 2013;61:1582–94.PubMedCrossRef
56.
Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, et al. Single-Cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity. 2019;50:253–71.PubMedCrossRef
57.
Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A unique microglia type associated with restricting development of Alzheimer’s Disease. Cell. 2017;169:1276–90.PubMedCrossRef
58.
Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, el Fatimy R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017;47:566-581.e9.PubMedPubMedCentralCrossRef
59.
Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YHE, et al. Epigenetic regulation of brain region-specific microglia clearance activity. Nat Neurosci. 2018;21:1049–60.PubMedPubMedCentralCrossRef
60.
Hohsfield LA, Najafi AR, Ghorbanian Y, Soni N, Crapser JD, Figueroa Velez DX, et al. Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave. Elife. 2021;10:8.CrossRef
61.
Boer K, Spliet WGM, van Rijen PC, Redeker S, Troost D, Aronica E. Evidence of activated microglia in focal cortical dysplasia. J Neuroimmunol. 2006;173:188–95.PubMedCrossRef
62.
van Vliet EA, Forte G, Holtman L, den Burger JCG, Sinjewel A, de Vries HE, et al. Inhibition of mammalian target of rapamycin reduces epileptogenesis and blood–brain barrier leakage but not microglia activation. Epilepsia. 2012;53:1254–63.PubMedCrossRef
63.
Tanaka Y, Matsuwaki T, Yamanouchi K, Nishihara M. Increased lysosomal biogenesis in activated microglia and exacerbated neuronal damage after traumatic brain injury in progranulin-deficient mice. Neuroscience. 2013;250:8–19.PubMedCrossRef
64.
Bechmann I, Peter S, Beyer M, Gimsa U, Nitsch R. Presence of B7–2 (CD86) and lack of B7–1 (CD(80) on myelin phagocytosing MHC-II-positive rat microglia is associated with nondestructive immunity in vivo. FASEB J. 2001;15:1086–8.PubMed
65.
Bohatschek M, Kloss CUA, Pfeffer K, Bluethmann H, Raivich G. B7.2 on activated and phagocytic microglia in the facial axotomy model: Regulation by interleukin-1 receptor type 1, tumor necrosis factor receptors 1 and 2 and endotoxin. J Neuroimmunol. 2004;156:132–45.PubMedCrossRef
66.
Laman JD, de Boer M, Hart T. Minireview CD40 in clinical inflammation: from multiple sclerosis to atherosclerosis. Dev Immunol. 1998;8:78.
67.
Bercury KK, Macklin WB. Dynamics and mechanisms of CNS myelination. Dev Cell. 2015;9:447–58.CrossRef
68.
Bouyssi-Kobar M, du Plessis AJ, Mccarter R, Brossard-Racine M, Murnick J, Tinkleman L, et al. Third trimester brain growth in preterm infants compared with in utero healthy fetuses. Pediatrics. 2016;8:78.
69.
Kostović I, Jovanov-Milošević N. The development of cerebral connections during the first 20–45 weeks’ gestation. Semin Fetal Neonatal Med. 2006;11:415–22.PubMedCrossRef
70.
Amiel-Tison C, Gosselin J, Infante-Rivard C. Head growth and cranial assessment at neurological examination in infancy. Dev Med Child Neurol. 2002;89:6.
71.
Huang Y, Xu Z, Xiong S, Sun F, Qin G, Hu G, et al. Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat Neurosci. 2018;21:530–40.PubMedCrossRef
72.
Lloyd AF, Davies CL, Holloway RK, Labrak Y, Ireland G, Carradori D, et al. Central nervous system regeneration is driven by microglia necroptosis and repopulation. Nat Neurosci. 2019;22:1046–52.PubMedPubMedCentralCrossRef
73.
Liu Y, Given KS, Dickson EL, Owens GP, Macklin WB, Bennett JL. Concentration-dependent effects of CSF1R inhibitors on oligodendrocyte progenitor cells ex vivo and in vivo. Exp Neurol. 2019;318:32–41.PubMedPubMedCentralCrossRef
74.
Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS ONE. 2011;6:8.CrossRef
75.
Oosterhof N, Kuil LE, van der Linde HC, Burm SM, Berdowski W, van Ijcken WFJ, et al. Colony-Stimulating Factor 1 Receptor (CSF1R) regulates microglia density and distribution, but not microglia differentiation in vivo. Cell Rep. 2018;24:1203–17.PubMedCrossRef
76.
del Bigio MR. Pathophysiologic consequences of hydrocephalus. Neurosurg Clin N Am. 2001;12:639–49.PubMedCrossRef
77.
Ayannuga OA, Shokunbi MT, Naicker TA. Myelin sheath injury in kaolin-induced hydrocephalus: a light and electron microscopy study. Pediatr Neurosurg. 2016;51:61–8.PubMedCrossRef
78.
79.
Santos EN, Fields DR. Regulation of myelination by microglia. Sci Adv. 2021;7:50.CrossRef
80.
Ulfig N, Bohl J, Neudörfer F, Rezaie P. Brain macrophages and microglia in human fetal hydrocephalus. Brain Dev. 2004;26:307–15.PubMedCrossRef
81.
Harris CA, Morales DM, Arshad R, McAllister JP, Limbrick DD. Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction. Fluids Barriers CNS. 2021;18:89.CrossRef
82.
Glees P, Hasan M. Ultrastructure of human cerebral macroglia and microglia: maturing and hydrocephalic frontal cortex. Neurosurg Rev. 1990;13:231–42.PubMedCrossRef
83.
Ross EJ, Graham DL, Money KM, Stanwood GD. Developmental consequences of fetal exposure to drugs: What we know and what we still must learn. Neuropsychopharmacology. 2015;9:61–87.CrossRef
84.
Sminia T, de Groot CJA, Dijkstra CD, Koetsier JC, Polman CH. Macrophages in the central nervous system of the rat. Immunobiology. 1987;174:43–50.PubMedCrossRef
85.
Alliot F, Godin I, Pessac B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Dev Brain Res. 1999;117:145–52.CrossRef
86.
Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330:841–5.PubMedPubMedCentralCrossRef
87.
Zeger M, Popken G, Zhang J, Xuan S, Lu QR, Schwab MH, et al. Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. Glia. 2007;55:400–11.PubMedPubMedCentralCrossRef
88.
89.
Nemes-Baran AD, White DR, DeSilva TM. Fractalkine-dependent microglial pruning of viable oligodendrocyte progenitor cells regulates myelination. Cell Rep. 2020;32:34.CrossRef
90.
Arnold TD, Lizama CO, Cautivo KM, Santander N, Lin L, Qiu H, et al. Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction. J Exp Med. 2019;216:900–15.PubMedPubMedCentralCrossRef
91.
Schafer DP, Stevens B. Microglia function in central nervous system development and plasticity. Cold Spring Harb Perspect Biol. 2015;7:789.CrossRef
92.
Torres L, Danver J, Ji K, Miyauchi JT, Chen D, Anderson ME, et al. Dynamic microglial modulation of spatial learning and social behavior. Brain Behav Immun. 2016;55:6–16.PubMedCrossRef
93.
Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat Commun. 2019;10:89.CrossRef
94.
Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19:1264–72.PubMedPubMedCentralCrossRef
95.
Yu L, Su X, Li S, Zhao F, Mu D, Qu Y. Microglia and their promising role in ischemic brain injuries: an update. Front Cell Neurosci. 2020;14:78.CrossRef
96.
Najafi AR, Crapser J, Jiang S, Ng W, Mortazavi A, West BL, et al. A limited capacity for microglial repopulation in the adult brain. Glia. 2018;66:2385–96.PubMedPubMedCentralCrossRef
97.
O’Neil SM, Witcher KG, McKim DB, Godbout JP. Forced turnover of aged microglia induces an intermediate phenotype but does not rebalance CNS environmental cues driving priming to immune challenge. Acta Neuropathol Commun. 2018;6:129.PubMedPubMedCentralCrossRef
98.
Zhang Y, Zhao L, Wang X, Ma W, Lazere A, Qian H-H, et al. Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation. Neuropathol Commun. 2018;89:5.
99.
Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, et al. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med. 2017;23:997–1003.PubMedCrossRef
100.
Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun. 2019;10:78.CrossRef
101.
Bisht K, Okojie KA, Sharma K, Lentferink DH, Sun YY, Chen HR, et al. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nat Commun. 2021;12:56.CrossRef
Metadata
Title
Early postnatal microglial ablation in the Ccdc39 mouse model reveals adverse effects on brain development and in neonatal hydrocephalus
Authors
Farrah N. Brown
Eri Iwasawa
Crystal Shula
Elizabeth M. Fugate
Diana M. Lindquist
Francesco T. Mangano
June Goto
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2023
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-023-00433-4

Other articles of this Issue 1/2023

Fluids and Barriers of the CNS 1/2023 Go to the issue

Research

Impact of aging on meningeal gene expression

Research

The maturation of iPS cell-derived brain microvascular endothelial cells by inducible-SOX18 expression

Research

Modelling idiopathic intracranial hypertension in rats: contributions of high fat diet and testosterone to intracranial pressure and cerebrospinal fluid production

Research

Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3

Research

Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17

Research

Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model

Advances in Alzheimer's

Alzheimer's research and care is changing rapidly. Keep up with the latest developments from key international conferences, together with expert insights on how to integrate these advances into practice.

This content is intended for healthcare professionals outside of the UK.

Supported by:
  • Lilly
Developed by: Springer Healthcare IME
Learn more
Image Credits