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Transcranial amelioration of inflammation and cell death after brain injury.
Open accessAbstract
Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.
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“Cx3cr1+ meningeal macrophages are observed dying within 30 min of injury induction, leading to formation of a “honeycomb” network of microglia at the glial limitans, likely preventing the spread of reactive oxygen species from the leptomeninges into the brain parenchyma”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Roth et al., 2013
In the citing paper
“For example, damage to the glia limitans superficialis after TBI results in a profound morphological transformation of the underlying microglia that depends on ATP release by surface-associated astrocytes and subsequent detection by microglial purinergic receptors (126).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [126]
In the citing paper
“Real-time imaging studies revealed that microglia transform into honeycomb- and jellyfish-like morphologies that provide barrier support and debris clearance (126).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [126]
In the citing paper
“TBI can disrupt vascular integrity in the meninges and brain parenchyma, resulting in leakage of materials from the blood supply into CNS (Fig. 4) (125-127).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [126]
In the citing paper
“In the absence of this transformation, the glia limitans leaked profoundly.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [126]
In the citing paper
“In the minutes following TBI, microglia are recruited via purinergic signaling to clear necrotic debris and adopt a phagocytic state [100,107,108].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [107]
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Citations
Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · cited 1×
“Honeycomb microglial networks circumscribed individual surviving astrocytes in the glial limitans and were induced to do so by release of ATP from connexin hemichannels and detection by purinergic receptors (P2X4 and P2Y12) 16, 17, 19, 20 .”
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · cited 1×
“Honeycomb microglial networks circumscribed individual surviving astrocytes in the glial limitans and were induced to do so by release of ATP from connexin hemichannels and detection by purinergic receptors (P2X4 and P2Y12) 16, 17, 19, 20 .”
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · cited 1×
“In the absence of GSH, the brain responded to damage by eliciting an anatomically partitioned sterile immune reaction 18 .”
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W.-B., & Julius, D. (2006) · Nature Neuroscience · doi:10.1038/nn1805 · Cited by 1,542 · cited 1×
“Honeycomb microglial networks circumscribed individual surviving astrocytes in the glial limitans and were induced to do so by release of ATP from connexin hemichannels and detection by purinergic receptors (P2X4 and P2Y12) 16, 17, 19, 20 .”
Animal models of traumatic brain injury
Xiong, Y., Mahmood, A., & Chopp, M. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3407 · Cited by 1,456 · cited 1×
“moderate, and severe forms of injury 5 , but therapeutic research in these models has not yet translated successfully into the clinic 4, 13 .”
Changing patterns in the epidemiology of traumatic brain injury
Roozenbeek, B., Maas, A. I. R., & Menon, D. K. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.22 · Cited by 1,405
Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation
McDonald, B., Pittman, K., Menezes, G. B., Hirota, S. A., Slaba, I., Waterhouse, C. C. M., Beck, P. L., Muruve, D. A., & Kubes, P. (2010) · Science · doi:10.1126/science.1195491 · Cited by 1,210 · cited 1×
“While microglia protected the parenchyma, myelomonocytic cells invaded the damaged meninges in a P2X7-and pannexin-dependent manner consistent with a recent study showing P2X7-dependent neutrophil recruitment into the injured liver 21 .”
Free Radical Pathways in CNS Injury
LEWÉN, A., MATZ, P., & CHAN, P. H. (2000) · Journal of Neurotrauma · doi:10.1089/neu.2000.17.871 · Cited by 759 · cited 1×
“ROS is commonly observed in TBI lesions 7, 8 , and transcranial delivery of GSH preserved the glial limitans, reduced cell death, and eliminated the sterile injury response.”
Faust, N., Varas, F., Kelly, L. M., Heck, S., & Graf, T. (2000) · Blood · doi:10.1182/blood.v96.2.719 · Cited by 751
Cited by
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Items 201–300 of 574
Elucidation of monocyte/macrophage dynamics and function by intravital imaging
Rua, R., & McGavern, D. B. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.4ri0115-006rr · Cited by 46
Haber, M., Hutchinson, E. B., Sadeghi, N., Cheng, W. H., Namjoshi, D., Cripton, P. A., Irfanoglu, M. O., Wellington, C. L., Diaz-Arrastia, R. R., & Pierpaoli, C. M. (2017) · eNeuro · doi:10.1523/eneuro.0164-17.2017 · Cited by 46
Regional mechanical and biochemical properties of the porcine cortical meninges
Walsh, D. R., Ross, A. M., Malijauskaite, S., Flanagan, B. D., Newport, D. T., McGourty, K., & Mulvihill, J. J. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.09.004 · Cited by 44
Zhao, Z., Yan, L., Wen, J., Satyanarayanan, S. K., Feng, Y., Lu, J., Liu, Y., & Su, H. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad033 · Cited by 45
Koletar, M. M., Dorr, A. E., Brown, M. E., McLaurin, J., & Stefanovic, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-41966-9 · Cited by 43
From cartoon to real time MRI: in vivo monitoring of phagocyte migration in mouse brain
Mori, Y., Chen, T., Fujisawa, T., Kobashi, S., Ohno, K., Yoshida, S., Tago, Y., Komai, Y., Hata, Y., & Yoshioka, Y. (2014) · Scientific Reports · doi:10.1038/srep06997 · Cited by 42
Liang, F., Luo, C., Xu, G., Su, F., He, X., Long, S., Ren, H., Liu, Y., Feng, Y., & Pei, Z. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.05.006 · Cited by 42
Open Challenges and Opportunities in Piezoelectricity for Tissue Regeneration
Deng, X., Zhuang, Y., Cui, J., Wang, L., Zhan, H., Wang, X., Lin, K., & Yuan, C. (2025) · Advanced Science · doi:10.1002/advs.202510349 · Cited by 45
Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells
Bozic, I. D., Savić, D. Z., Stevanović, I. D., Peković, S., Nedeljković, N., & Lavrnja, I. C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00351 · Cited by 44
Levy, D., Edut, S., Baratz-Goldstein, R., Rubovitch, V., Defrin, R., Bree, D., Gariépy, H. D. B., Zhao, J., & Pick, C. G. (2015) · Cephalalgia · doi:10.1177/0333102415617412 · Cited by 41
Yu, W., Parakramaweera, R., Teng, S. L., Gowda, M., Sharad, Y., Thakker‐Varia, S., Alder, J., & Sesti, F. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2273-16.2016 · Cited by 41
“…animals to mild to moderate traumatic brain injury—which is associated with extensive oxidation during the secondary injury (Corps et al., 2015; Hiebert et al., 2015; Shen et al., 2016)— using the lateral fluid percussion (LFP) method (McIntosh et al., 1989; Alder et al., 2011; Roth et al., 2014).”
MethodAlarmins and central nervous system inflammation in HIV ‐associated neurological disorders
Gougeon, M. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12570 · Cited by 41
Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction
Luo, C., Ren, H., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J., Pei, Z., Su, K., & Su, H. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.05.028 · Cited by 43
Targeting P2X4 and P2X7 receptors in multiple sclerosis
Domercq, M., & Matute, C. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.03.010 · Cited by 43
Wang, C., Zhao, C., Liu, W., Huang, X., Deng, Y., Jiang, J., & Li, W. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2019.6460 · Cited by 40
Bhat, S. A., Henry, R. J., Blanchard, A. C., Stoica, B. A., Loane, D. J., & Faden, A. I. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14954 · Cited by 42
Lan, Y., Wang, H., Chen, A., & Zhang, J. (2022) · Immunology · doi:10.1111/imm.13517 · Cited by 45
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesisPreprint
Bolte, A. C., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., Natale, N. R., Ennerfelt, H. E., Frost, E. L., Lammert, C. R., Kipnis, J., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/817023 · Cited by 41
Wang, Y., Tian, J., Liu, D., Li, T., Mao, Y., & Zhu, C. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14794 · Cited by 45
“63,64 HMGB1 strongly stimulates astrocytes to secrete various chemokines, including neutrophil chemokines (CXCL1, CXCL2, and CCL3) and T-cell chemokines (CXCL1, CCL2, CCL5, and CCL20).”
BackgroundNeuroimmune interactions in the development and chronification of migraine headache
Zhang, J., Simoes, R., Guo, T., & Cao, Y. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.08.009 · Cited by 44
Fu, X., Zhang, Y., Chen, G., Mao, G.-Y., Tang, J., Jin, X., Han, Y., Chen, H., & Ding, L. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03251-y · Cited by 42
“These mediators are crucial in the local inflammatory response, influencing neurons and other glial cells [29].”
The role of NLRP3 in traumatic brain injury and its regulation by pioglitazone
Yi, H. J., Lee, J. E., Lee, D. H., Kim, Y. I., Cho, C. B., Kim, I. S., Sung, J. H., & Yang, S. H. (2019) · Journal of neurosurgery · doi:10.3171/2019.6.jns1954 · Cited by 40
Mapping the Connectome Following Traumatic Brain Injury
Hannawi, Y., & Stevens, R. D. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0642-9 · Cited by 41
Rovegno, M., Soto, P., Sáez, P. J., Naus, C. C. G., Sáez, J. C., & Rommy von Bernhardi, M. (2015) · Glia · doi:10.1002/glia.22808 · Cited by 39
Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion
Mutch, W. A. C., Ellis, M. J., Graham, M. R., Wourms, V., Raban, R., Fisher, J. A., Mikulis, D. J., Leiter, J., & Ryner, L. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102181 · Cited by 42
Eles, J. R., Vazquez, A. L., Kozai, T. D. Y., & Cui, X. T. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.12.031 · Cited by 41
“This early migratory window likely represents inflammatory mobilization to the craniotomy and implant site as the initiation of wound healing [30].”
BackgroundInfluentialBarkaway, A., Attwell, D., & Korte, N. (2022) · Neurophotonics · doi:10.1117/1.nph.9.3.031914 · Cited by 38
Xue, F., Sun, D., Wang, Z., Yu, Z., Liu, W., Pu, Y., Wang, D., Huang, A., Liu, M., Xiang, Z., et al. (2017) · Neuroscience Bulletin · doi:10.1007/s12264-017-0153-y · Cited by 38
“jellyfish-like shape are more phagocytic, and tend to be pro-inflammatory, while branched microglia tend to be resting or anti-inflammatory [25].”
BackgroundIgnowski, E., Winter, A. N., Duval, N., Fleming, H., Wallace, T., Manning, E., Koza, L. A., Huber, K. M., Serkova, N. J., & Linseman, D. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.026 · Cited by 38
“In this context, a prior study using a novel closed skull injury model in mice demonstrated that transcranial administration of GSH ameliorated brain injury and neuroinflammation [42].”
Purinergic signaling in Alzheimer’s disease
Erb, L., Woods, L. T., Khalafalla, M. G., & Weisman, G. A. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.10.014 · Cited by 39
CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain
Wang, L., Zheng, J., Zhao, S., Wan, Y., Wang, M., Bosco, D. B., Kuan, C.-Y., Richardson, J. R., & Wu, L. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114120 · Cited by 42
Chan, S., Evans, K. C., Rosen, B. R., Song, T.-Y., & Kwong, K. K. (2014) · Brain Injury · doi:10.3109/02699052.2014.974209 · Cited by 37
α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson’s Disease Pathogenesis
Butkovich, L. M., Houser, M. C., & Tansey, M. G. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00626 · Cited by 39
“In a healthy brain, the inflammatory response resolves relatively quickly, with normal brain function restored (Roth et al., 2014; Laumet et al., 2018).”
BackgroundPersistent neuroinflammation and behavioural deficits after single mild traumatic brain injury
Drieu, A., Lanquetin, A., Prunotto, P., Gulhan, Z., Pédron, S., Vegliante, G., Tolomeo, D., Sérrière, S., Vercouillie, J., Galineau, L., et al. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221119288 · Cited by 42
“It also has been shown in another model of miTBI consisting on compressing the thinned-skull bone, microglia can become activated.(40) Although one could argue that Iba1 is not a specific marker for microglial cells as it can also reflect infiltrating monocytes,(38) the absence of cerebrovascular inflammation in our m…”
MethodFrieler, R. A., Nadimpalli, S., Boland, L. K., Xie, A., Kooistra, L. J., Song, J., Chung, Y., Cho, K. W., Lumeng, C. N.-K., Wang, M. M., et al. (2015) · Brain Research · doi:10.1016/j.brainres.2015.07.011 · Cited by 34
Chronic Traumatic Encephalopathy: Is Latency in Symptom Onset Explained by Tau Propagation?Preprint
Kriegel, J., Papadopoulos, Z., & McKee, A. C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024059 · Cited by 38
Central Nervous System: (Immunological) Ivory Tower or Not?
Marin, I. A., & Kipnis, J. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.122 · Cited by 36
He, J., Huang, Y., Liu, H., Sun, X., Wu, J., Zhang, Z., Liu, L., Zhou, C., Jiang, S., Huang, Z., et al. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113462 · Cited by 36
Engel, T., Brennan, G. P., Sanz‐Rodriguez, A., Alves, M., Beamer, E. H., Watters, O., Henshall, D. C., & Jimenez-Mateos, E. M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.11.007 · Cited by 36
INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury
Calabrese, B., Jones, S. L., Shiraishi‐Yamaguchi, Y., Lingelbach, M., Manor, U., Svitkina, T., Higgs, H. N., Shih, A. Y., & Halpain, S. (2022) · Nature Communications · doi:10.1038/s41467-022-33268-y · Cited by 37
Benromano, T., Defrin, R., Ahn, A. H., Zhao, J., Pick, C. G., & Levy, D. (2014) · European Journal of Pain · doi:10.1002/ejp.583 · Cited by 35
Gao, H., Yin, J., Shi, Y., Hu, H., Li, X., Xue, M., Cheng, W., Wang, Y., Li, X., Li, Y., et al. (2016) · Cardiovascular Therapeutics · doi:10.1111/1755-5922.12245 · Cited by 35
Repositioning drugs for traumatic brain injury - N-acetyl cysteine and Phenserine
Hoffer, B. J., Pick, C. G., Hoffer, M. E., Becker, R. E., Chiang, Y. H., & Greig, N. H. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0377-1 · Cited by 35
Kornguth, S. E., Rutledge, N., Perlaza, G., Bray, J., & Hardin, A. (2017) · Brain Sciences · doi:10.3390/brainsci7120164 · Cited by 35
Meningeal lymphatics, immunity and neuroinflammation
Frederick, N. M., & Louveau, A. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.010 · Cited by 33
Permeability of the Blood–Brain Barrier after Traumatic Brain Injury: Radiological Considerations
Amoo, M., O’Halloran, P. J., Henry, J. H., Husien, M. B., Brennan, P., Campbell, M., Caird, J., & Curley, G. F. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7545 · Cited by 36
Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity
Zhao, J., Blaeser, A. S., & Levy, D. (2021) · Pain · doi:10.1097/j.pain.0000000000002229 · Cited by 35
Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow
Rustenhoven, J., Tanumihardja, C., & Kipnis, J. (2021) · Circulation Research · doi:10.1161/circresaha.121.318173 · Cited by 38
Ahn, S. J., Taoka, T., Moon, W., & Naganawa, S. (2022) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.28117 · Cited by 38
Harch, P. G. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.815056 · Cited by 38
CNS and CNS diseases in relation to their immune system
Xu, J., Ma, C.-Y., Hua, M., Li, J., Xiang, Z., & Wu, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1063928 · Cited by 36
Monitoring in vivo function of cortical microglia
Brawek, B., & Garaschuk, O. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.02.011 · Cited by 35
Zhou, L., Liu, H., Zhang, B., Wei, C., Zhou, S., Huang, X.-Y., Zhong, X., Zhang, L., Bi, W., Liu, J., et al. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202314330 · Cited by 34
In VivoImaging of CNS Injury and Disease
Akassoglou, K., Merlini, M., Rafalski, V. A., Real, R., Liang, L., Jin, Y., Dougherty, S. E., Paola, V. D., Linden, D. J., Misgeld, T., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1826-17.2017 · Cited by 33
“For example, drug delivery through a thinned skull and study of microglia responses using in vivo two-photon imaging allows assessment of drug compounds within 24 h after traumatic brain injury (Roth et al., 2014).”
BackgroundCloyd, R., Koren, S. A., & Abisambra, J. F. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00403 · Cited by 34
“, 1984; Runge et al., 1984; Fornasiero et al., 1987). Lin and Koretsky (1997) first demonstrated manganese contrast can be used as a noninvasive, direct measurement of neuronal function. Lin and Koretsky (1997) administered manganese chloride via a peripheral intravenous injection and reported imaging enhancement in s…”
BackgroundMethodInfluentialMurugan, M., Ravula, A. R., Gandhi, A., Vegunta, G., Mukkamalla, S., Mujib, W., & Chandra, N. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.029 · Cited by 33
Fan, F., Xu, N., Sun, Y., Li, X., Gao, X., Yi, X., Zhang, Y., Meng, X., & Lin, J. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00647 · Cited by 35
Neuro-Inflammation in Pediatric Traumatic Brain Injury—from Mechanisms to Inflammatory Networks
Fraunberger, E. A., & Esser, M. J. (2019) · Brain Sciences · doi:10.3390/brainsci9110319 · Cited by 36
“further ATP, glutamate, and S100β release (via MAPK signaling [60]), microglia recruitment to the site of injury, and the subsequent activation of both astrocytes and microglia [61].”
BackgroundMeningeal blood–brain barrier disruption in acute traumatic brain injury
Turtzo, L. C., Jikaria, N. R., Cota, M. R., Williford, J. P., Uche, V., Davis, T. S., MacLaren, J. M., Moses, A. D., Parikh, G. Y., Castro, M. A., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa143 · Cited by 33
“Traumatic meningeal enhancement (TME), associated with meningeal injury, can be observed on contrast-enhanced MRI after acute TBI (Roth et al., 2014; Ricciardi et al., 2017; Davis et al., 2020) and at 2 weeks after injury (Kim et al.”
BackgroundExtrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages
Amann, L., Fell, A., Monaco, G., Sankowski, R., Wu, H., Jordão, M. J. C., Borst, K., Fliegauf, M., Masuda, T., Ardura-Fabregat, A., et al. (2024) · Science Immunology · doi:10.1126/sciimmunol.adh1129 · Cited by 34
Hammer, D. X., Lozzi, A., Abliz, E., Greenbaum, N., Agrawal, A., Krauthamer, V., & Welle, C. G. (2014) · Biomedical Optics Express · doi:10.1364/boe.5.002823 · Cited by 32
Tang, H., He, K., Zhao, K., Chen, Z., Wu, W., Jin, W., Yang, L., & Xie, B. (2023) · Journal of Neurotrauma · doi:10.1089/neu.2023.0150 · Cited by 31
The immunology of stroke and dementia
Iadecola, C., & Anrather, J. (2025) · Immunity · doi:10.1016/j.immuni.2024.12.008 · Cited by 37
Liu, L., Zhang, X., Chai, Y., Zhang, J., Deng, Q., & Chen, X. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07336-2 · Cited by 41
Mast cells regulate the brain-dura interface and CSF dynamics
Mamuladze, T., Zaninelli, T. H., Smyth, L. C. D., Wu, Y., Abramishvili, D., Silva, R. D. M., Imbiakha, B., Verhaege, D., Du, S., Papadopoulos, Z., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.046 · Cited by 34
Hubert, V., Dumot, C., Ong, E., Amaz, C., Canet‐Soulas, E., Chauveau, F., & Wiart, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-46566-1 · Cited by 34
Zhang, J., Zhou, R., Xiang, C., Fan, F., Gao, J., Zhang, Y., Tang, S., Xu, H., & Yang, H. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15099 · Cited by 32
Gao, H., Di, J., Clausen, B. H., Wang, N., Zhu, X., Zhao, T., Chang, Y., Pang, M., Yang, Y., He, R., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112629 · Cited by 36
Liu, Q., Meng, H., Xie, W., Yu, H., & Zhang, Y. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.187047 · Cited by 31
Lu, M., Yan, X., Yun, S., & Chen, X. (2019) · Inflammation · doi:10.1007/s10753-019-01029-7 · Cited by 31
Meningeal T cells function in the central nervous system homeostasis and neurodegenerative diseases
Abbaoui, A., Fatoba, O., & Yamashita, T. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1181071 · Cited by 32
“Perhaps, they are typically present in the dura mater, and CSF serves as the main route driving meningeal T cells cytokines to the neural cells within different CNS regions through paravascular influx toward glial limitans (Roth et al., 2014).”
Backgroundvon Leden, R. E., Parker, K. N., Bates, A. A., Noble‐Haeusslein, L. J., & Donovan, M. H. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.004 · Cited by 28
“There is a growing interest in neutrophils in TBI, implicating their involvement in secondary injury (Dickens et al., 2017; Makinde et al., 2017; Roth et al., 2014; Russo et al., 2018; Zhao et al., 2017).”
BackgroundFast microglial activation after severe traumatic brain injuries
Lier, J., Ondruschka, B., Bechmann, I., & Dreßler, J. (2020) · International Journal of Legal Medicine · doi:10.1007/s00414-020-02308-x · Cited by 33
Abd‐El‐Basset, E. M., Rao, M. S. R., & Alsaqobi, A. K. (2020) · Neuroscience Insights · doi:10.1177/2633105520947081 · Cited by 30
Silva, L. F. A., Reschke, C. R., Nguyen, T. N., Langa, E., Sanz‐Rodriguez, A., Gerbatin, R. R., Temp, F. R., de Freitas, M. L., Conroy, R. M., Brennan, G. P., et al. (2020) · Molecular Brain · doi:10.1186/s13041-020-00653-x · Cited by 29
Wu, K., Huang, D., Zhu, C., Kasanga, E. A., Zhang, Y., Yu, E., Zhang, H., Ni, Z., Ye, S., Zhang, C., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1428-1 · Cited by 30
“In the early stages of acute brain injury, injured cells release a series of harmful signals to produce immune responses [44].”
BackgroundTong, S., Xie, L., Xie, X., Xu, J., You, Y., Sun, Y., Zhou, S., Ma, C., Jiang, G., Ma, F., et al. (2023) · Advanced Science · doi:10.1002/advs.202304284 · Cited by 29
Evans, T. M., Jaramillo, C. A., Sataranatarajan, K., Watts, L. T., Sabia, M., Qi, W., & Remmen, H. V. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.04.041 · Cited by 30
“It is thought that elevated oxidative damage and inflammation act in a cyclic fashion and propagate secondary injury downstream of the site of TBI (Roth et al., 2014).”
BackgroundZhao, J., & Levy, D. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0115-18.2018 · Cited by 29
“The concentration of levcromakalim expected to be attained at the superficial cortex was estimated to be 100-1000 times lower, (Moore et al., 1982; Roth et al., 2014; Zhao et al., 2016).”
BackgroundPhotobiomodulation therapy for repeated closed head injury in rats
Yang, B., Xu, J., Li, Y., Dong, Y., Li, Y., Tucker, L. D., Yang, L., Zong, X., Wu, C., Xu, T. J., et al. (2019) · Journal of Biophotonics · doi:10.1002/jbio.201960117 · Cited by 30
Zhang, J., Yi, T., Cheng, S., & Zhang, S. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106715 · Cited by 29
Liu, Z., Chen, N.-Y., Tu, P., Wu, C., Chiu, S., Huang, Y., Lim, S., & Yip, P. K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176291 · Cited by 29
“In this study, the focus on the mechanism of action of improved functional outcome by DHA was on edema as a breakdown of BBB is one of the main contributors interfering brain recovery from secondary damage [32].”
BackgroundHubert, V., Hristovska, I., Kárpáti, S., Benkeder, S., Dey, A. K., Dumot, C., Amaz, C., Chounlamountri, N., Watrin, C., Comte, J., et al. (2021) · Advanced Science · doi:10.1002/advs.202101433 · Cited by 34
Mehina, E. M. F., Taylor, S. L., Boghozian, R., White, E. R., Choi, S. E., Cheema, M. S., Körbelin, J., & Brown, C. E. (2021) · Science Advances · doi:10.1126/sciadv.abg2712 · Cited by 28
Sweeney, A. M., Plá, V., Du, T., Liu, G., Sun, Q., Peng, S., Plog, B. A., Kress, B. T., Wang, X., Mestre, H., et al. (2019) · Journal of Visualized Experiments · doi:10.3791/59774 · Cited by 34
Obaid, A., Wu, Y., Hanna, M., Nix, W. D., Ding, J., & Melosh, N. A. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/454520 · Cited by 30
Martin, S. P., & Leeman-Markowski, B. A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2023.1287545 · Cited by 30
Development of an improved and specific inhibitor of NADPH oxidase 2 to treat traumatic brain injury
Mason, H. D., Rai, G., Kozyr, A. V., Jonge, N. D., Gliniewicz, E. F., Berg, L. J., Wald, G., Dorrier, C., Henderson, M. J., Zakharov, A. V., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102611 · Cited by 29
Potential protection of vitamin C against liver-lesioned mice
Su, M., Chen, H., Wei, C., Chen, N., & Wu, W. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.07.034 · Cited by 28
Guo, Y., Du, M., Li, R., Li, K., Huang, X., Duan, D., Ai, X., Yao, F., Zhang, L., Hu, Z., et al. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.04.008 · Cited by 28
Genetic neutrophil deficiency ameliorates cerebral ischemia-reperfusion injury
Frieler, R. A., Chung, Y., Ahlers, C. G., Gheordunescu, G., Song, J., Vigil, T. M., Shah, Y. M., & Mortensen, R. M. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.08.016 · Cited by 29
Sirt1 Regulates Oxidative Stress in Oxygen-Glucose Deprived Hippocampal Neurons
Shi, L., Zhang, J., Wang, Y., Hao, Q., Chen, H., & Cheng, X. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.00455 · Cited by 27
Role for Functional SOD2 Polymorphism in Pulmonary Arterial Hypertension in a Chinese Population
Xu, M. J., Xu, M., Han, L., Yuan, C., Mei, Y., Zhang, H., Chen, S., Sun, K., & Zhu, B. (2017) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph14030266 · Cited by 28
Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases
Yang, J., & Li, Q.-Q. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00143 · Cited by 21
The Role of NKT Cells in Glioblastoma
Brettschneider, E. E. S., & Terabe, M. (2021) · Cells · doi:10.3390/cells10071641 · Cited by 27
Microglia in CNS infections: insights from Toxoplasma gondii and other pathogens
Cowan, M. N., Sethi, I., & Harris, T. H. (2022) · Trends in Parasitology · doi:10.1016/j.pt.2021.12.004 · Cited by 27
Microglial STAT1-sufficiency is required for resistance to toxoplasmic encephalitis
Cowan, M. N., Kovacs, M. A., Sethi, I., Babcock, I. W., Still, K. M., Batista, S. J., O’Brien, C. A., Thompson, J. A., Sibley, L. A., Labuzan, S. A., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010637 · Cited by 24
Kang, J. H., & Ko, Y. T. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10424 · Cited by 27
Gariépy, H. D. B., Zhao, J., & Levy, D. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16650217 · Cited by 26
T cells in the brain inflammation
Yoshimura, A., Ohyagi, M., & Ito, M. (2022) · Advances in immunology · doi:10.1016/bs.ai.2022.10.001 · Cited by 29
Metadata
- Authors
- Roth, T. L., Nayak, D., Atanasijevic, T., Koretsky, A. P., Latour, L. L., & McGavern, D. B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- McGavern, Dorian B.
- Venue
- Nature
- Published
- 2013-12-08
- Volume
- 505
- Issue
- 7482
- Pages
- 223-228
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3930079
- OpenAlex
- W2055797258
- Cited by
- 574
- References
- 27
- Citations by year
- 2026: 30 · 2025: 46 · 2024: 45 · 2023: 42 · 2022: 62 · 2021: 50 · 2020: 49 · 2019: 51 · 2018: 48 · 2017: 39 · 2016: 50 · 2015: 38 · 2014: 24
- FWCI
- 23.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (ZIANS003112)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- traumatic brain injury, meningeal inflammation, purinergic receptor antagonists, glutathione, reactive oxygen species, microglia, neutrophils, vascular injury, neuroinflammation, intravital microscopy
- MeSH terms
- Administration, Topical, Animals, Antioxidants, Astrocytes, Brain, Brain Injuries, Disease Models, Animal, Encephalitis, Glutathione, Humans, Male, Meninges, Neutrophils, Skull, Glasgow Coma Scale, Cell Death, Rats, Sprague-Dawley, Reactive Oxygen Species, Microglia, Receptors, Purinergic P2, Neuroprotective Agents, Intracranial Hemorrhages, Mice, Rats, Receptors, Purinergic P2X7, Purinergic P2 Receptor Antagonists
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