Neuroimmune cleanup crews in brain injury

Bolte, Ashley C.; Lukens, John R.

doi:10.1016/j.it.2021.04.003

Cited by 42 publications

(25 citation statements)

References 121 publications

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“…The next sections will highlight how meningeal cell types and structures respond to CNS injury (traumatic brain injury, stroke, spinal cord injury), infections (meningitis), and disease (multiple sclerosis, cancer, Alzheimer’s disease) ( Figure 3 ). We also recommend several other comprehensive recent reviews that highlight the meningeal vasculature, immune cells, and lymphatics/glymphatics in disease ( Rasmussen et al, 2018 ; Rua and McGavern, 2018 ; Mastorakos and McGavern, 2019 ; Alves de Lima et al, 2020 ; Bolte and Lukens, 2021 ).…”

Section: Meningeal Response To Injury and Diseasementioning

confidence: 99%

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Derk

Jones

Como

et al. 2021

Front. Cell. Neurosci.

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The meninges are the fibrous covering of the central nervous system (CNS) which contain vastly heterogeneous cell types within its three layers (dura, arachnoid, and pia). The dural compartment of the meninges, closest to the skull, is predominantly composed of fibroblasts, but also includes fenestrated blood vasculature, an elaborate lymphatic system, as well as immune cells which are distinct from the CNS. Segregating the outer and inner meningeal compartments is the epithelial-like arachnoid barrier cells, connected by tight and adherens junctions, which regulate the movement of pathogens, molecules, and cells into and out of the cerebral spinal fluid (CSF) and brain parenchyma. Most proximate to the brain is the collagen and basement membrane-rich pia matter that abuts the glial limitans and has recently be shown to have regional heterogeneity within the developing mouse brain. While the meninges were historically seen as a purely structural support for the CNS and protection from trauma, the emerging view of the meninges is as an essential interface between the CNS and the periphery, critical to brain development, required for brain homeostasis, and involved in a variety of diseases. In this review, we will summarize what is known regarding the development, specification, and maturation of the meninges during homeostatic conditions and discuss the rapidly emerging evidence that specific meningeal cell compartments play differential and important roles in the pathophysiology of a myriad of diseases including: multiple sclerosis, dementia, stroke, viral/bacterial meningitis, traumatic brain injury, and cancer. We will conclude with a list of major questions and mechanisms that remain unknown, the study of which represent new, future directions for the field of meninges biology.

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Section: Meningeal Response To Injury and Diseasementioning

confidence: 99%

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Derk

Jones

Como

et al. 2021

Front. Cell. Neurosci.

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“…Recent data point to a crucial role of the meningeal lymphatic system in modulating inflammation in the CNS 42 and that meningeal lymphatic drainage function could be targeted to mitigate neuroinflammation in aged mice subjected to closed head TBI. 10 Our data indicate that sTBI with a dural breach is associated with a marked local inflammatory response, with the production of monocyte- and leucocyte-recruiting chemokines driving the accumulation of myeloid cells, and that this was more prominent in aged mice.…”

Section: Discussionmentioning

confidence: 99%

Ageing is associated with maladaptive immune response and worse outcome after traumatic brain injury

Moro

Pischiutta

Portet

et al. 2022

Brain Communications

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Traumatic brain injury is increasingly common in older individuals. Older age is one of the strongest predictors for poor prognosis after brain trauma, a phenomenon driven by the presence of extra-cranial comorbidities as well as pre-existent pathologies associated with cognitive impairment and brain volume loss (such as cerebrovascular disease or age-related neurodegeneration). Furthermore, ageing is associated with a dysregulated immune response, which includes attenuated responses to infection and vaccination, and a failure to resolve inflammation leading to chronic inflammatory states. In traumatic brain injury, where the immune response is imperative for the clearance of cellular debris and survey of the injured milieu, an appropriate, self-limiting response is vital to promote recovery. Currently, our understanding of age-related factors that contribute to outcome is limited; but a more complete understanding is essential for development of tailored therapeutic strategies to mitigate the consequences of traumatic brain injury. Here we show greater functional deficits, white matter abnormalities, and worse long term outcomes in aged compared to young C57BL/6J mice after either moderate or severe traumatic brain injury. These effects are associated with altered systemic, meningeal and brain tissue immune response. Importantly, the impaired acute systemic immune response in the mice was similar to findings observed in our clinical cohort. Traumatic brain injured patient cohort over 70 years of age, showed lower monocyte and lymphocyte counts compared with those under 45 years. In mice, traumatic brain injury was associated with alterations in peripheral immune subsets, which differed in aged compared with adult mice. There was a significant increase in transcription of immune and inflammatory genes in the meninges post-traumatic brain injury, including monocyte/leucocyte-recruiting chemokines. Immune cells were recruited to the region of the dural injury, with a significantly higher number of CD11b+ myeloid cells in aged compared with adult mice. In brain tissue, when compared to young adult mice, we observed a more pronounced and widespread reactive astrogliosis one month after trauma in aged mice, sustained by an early and persistent induction of proinflammatory astrocytic state. These findings provide important insights regarding age-related exacerbation of neurological damage after brain trauma.

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“…Traumatic brain injury (TBI) increases the risk of other neurological and mental disorders, including chronic traumatic encephalopathy, AD, anxiety, depression and personality disorders ( Bolte and Lukens, 2021 ). TBI induces the release of Aβ and C-tau.…”

Section: Central Nervous System Diseasesmentioning

confidence: 99%

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

Zhang

2022

Front. Aging Neurosci.

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The glymphatic system, a recently discovered macroscopic waste removal system in the brain, has many unknown aspects, especially its driving forces and relationship with sleep, and thus further explorations of the relationship between the glymphatic system and a variety of possible related diseases are urgently needed. Here, we focus on the progress in current research on the role of the glymphatic system in several common central nervous system diseases and mood disorders, discuss the structural and functional abnormalities of the glymphatic system which may occur before or during the pathophysiological progress and the possible underlying mechanisms. We emphasize the relationship between sleep and the glymphatic system under pathological conditions and summarize the common imaging techniques for the glymphatic system currently available. The perfection of the glymphatic system hypothesis and the exploration of the effects of aging and endocrine factors on the central and peripheral regulatory pathways through the glymphatic system still require exploration in the future.

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Neuroimmune cleanup crews in brain injury

Cited by 42 publications

References 121 publications

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Ageing is associated with maladaptive immune response and worse outcome after traumatic brain injury

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

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