Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1754 2022-06-16 19:13:54 |
2 layout + 1 word(s) 1755 2022-06-17 03:48:06 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Preininger, M.; Kaufer, D. Astrocyte Functions. Encyclopedia. Available online: (accessed on 25 April 2024).
Preininger M, Kaufer D. Astrocyte Functions. Encyclopedia. Available at: Accessed April 25, 2024.
Preininger, Marcela, Daniela Kaufer. "Astrocyte Functions" Encyclopedia, (accessed April 25, 2024).
Preininger, M., & Kaufer, D. (2022, June 16). Astrocyte Functions. In Encyclopedia.
Preininger, Marcela and Daniela Kaufer. "Astrocyte Functions." Encyclopedia. Web. 16 June, 2022.
Astrocyte Functions

Astrocytes are stellated glial cells that interface with nearly every functional element of the brain. They are the most abundant glial cells in the brain and can comprise up to 50% of the tissue volume in some regions. Their branch-like processes surround neurons, axons, synapses, and blood vessels, and perform numerous functions that are essential for brain homeostasis and neural functioning.

astrocytes senescence blood–brain barrier

1. Introduction

Age-onset neurodegenerative disorders such as Alzheimer’s disease (AD) and related dementias (ADRD) are debilitating conditions that progressively impair the memory, cognition, and daily functioning of afflicted individuals. As the average lifespan has increased in developed nations, so has the prevalence of symptomatic AD. An estimated 6.2 million adults aged 65 and older are living with Alzheimer’s dementia, presenting a substantial societal burden [1]. However, despite decades of research, negligible progress has been made in developing effective disease-modifying treatments capable of halting or reversing AD progression and associated cognitive decline. The unsatisfactory clinical trial outcomes of experimental AD therapies indicate the need for a greater understanding of the age-related processes that drive neurodegenerative diseases.

2. Astrocyte Functions

Astrocytes are stellated glial cells that interface with nearly every functional element of the brain. They are the most abundant glial cells in the brain and can comprise up to 50% of the tissue volume in some regions [2]. Their branch-like processes surround neurons, axons, synapses, and blood vessels, and perform numerous functions that are essential for brain homeostasis and neural functioning [3]. Therefore, astrocytes play a pivotal role in preserving brain health, as well as driving pathogenic processes [4][5]. The understanding of astrocyte functions is continually growing as researchers study this heterogenous population of cells under different conditions, and it is increasingly evident that astrocytes perform unique functions, depending on their temporal and regional location within the brain [6][7][8][9]. Here, the researchers briefly review the astrocyte functions related to neuronal support, immune modulation, and regulation of the blood–brain barrier (BBB), as three factors that go awry in aging and disease.

2.1. Neuronal Support

At the macrostructural level, astrocytes help form a functional glial network that extends from the ependyma to the pial surface via gap junctions [10][11]. The perivascular feet of astrocytes associate with the parenchymal basal lamina to form a plexus called the glia limitans. This thin, but dense, structure surrounds the pia mater, subpial space, and perivascular spaces, and plays an essential role in controlling the movement of substances from the blood or cerebrospinal fluid (CSF) into the brain parenchyma, where neurons are located [12].
In addition to their role in barrier function, astrocytes maintain the optimal conditions required for neurotransmission within the cerebral microenvironment. To transmit a signal, neurotransmitters are released from an axon terminal into the synaptic cleft, where they interact with post-synaptic receptors. Ending the transmission requires neurotransmitter uptake from the synaptic cleft by neurons and astrocytes. While neurons primarily uptake the inhibitory transmitter, gamma-amino butyric acid (GABA), astrocytes are responsible for the uptake and metabolism of the excitatory amino acid, glutamate [13][14][15]. Additionally, the propagation of nerve impulses involves cellular depolarization, which causes local extracellular changes in ion concentration. Astrocytes contain ion channels, enzymes, and receptors that enable them to modify extracellular ion concentrations and pH following depolarization to restore the surrounding milieu to its resting state [16][17][18][19]. Astrocytes are also critical in removing harmful metabolites and waste products from the brain. They can directly metabolize some soluble waste products, such as ammonia; alternatively, they collect and shuttle unwanted metabolites and soluble proteins, such as amyloid beta (Aβ) to the vasculature for elimination via the glymphatic system [15][20][21].
In addition to maintaining the cerebral microenvironment, astrocytes also participate in neurotransmission and are critical in shaping the complex circuitry of the brain [22]. Astrocytes form tripartite complexes with presynaptic and postsynaptic nerve terminals, through which they help define synaptic connections. Astrocytes are the major source of extracellular matrix proteins, cell adhesion molecules, and neurotrophic factors in the central nervous system (CNS), which are essential in promoting neurite growth and elongation [23][24][25][26][27]. Additionally, astrocytes physically associate with neuronal synapses via perisynaptic astrocytic processes (PAPs) that regulate many aspects of their formation, maturation, and function [22][28]. For example, astrocytes regulate synaptogenesis via the secretion of thrombospondins (TSP) [29] and TGFβ1 [30][31], and can specifically control the maturation and plasticity of certain circuits via the secretion of Hevin and SPARC [32][33].

2.2. Immune Modulation

Compared to other tissues, the brain is a relatively immune-privileged site because it lacks a significant resident lymphoid population, and the BBB substantially restricts the entry of circulating immune cells into the CNS. Astrocytes are not immune cells per se, but are capable of many immune functions, including phagocytosis, antigen presentation, and facilitating immune-cell trafficking [34][35]. Therefore, astrocytes may produce pro- or anti-inflammatory cytokines, such as IL-1β, IL-6, TNF, IL-10, IL-27, and TGF-β in response to disease, stress, or injury [34][36]. Within the CNS, they communicate bidirectionally with microglia to coordinate defense responses [37]. Along with microglia, astrocytes phagocytose neuronal material including synapses, apoptotic neurons, and degenerating axons, as well as toxic proteins, such as Aβ plaques in AD and α-synuclein in Parkinson’s disease [38][39]. Consistent with their ability to present antigens, astrocytes express major histocompatibility complex (MHC) antigens that are upregulated in response to disease [40]. For example, high levels of astrocytic MHC-II were found in the brains of patients with Parkinson’s disease (PD), which correlated with the load of pathological, phosphorylated alpha synuclein (αSYN) [41]. Notably, perivascular and infiltrated CD4+ T cells were surrounded by MHC-II expressing astrocytes, indicating astrocyte–T-cell cross-talk in the PD brain [41]. Astrocytic MHC-I is upregulated during aging, which appears to be protective, since it is associated with preserved cognitive function [42].
Due to their proximity to blood vessels, astrocytes play a critical role in mediating reciprocal communication between CNS-resident cells and the immune system. Depending on the subsets involved, astrocytes respond to T-cell signals to either boost or limit CNS inflammation. For instance, pathogenic Th17 cells signal to astrocytes via GM-CSF and IL-17 to boost neurotoxic astrogliosis [43][44][45]; however, FOXP3+ regulatory T cells secrete amphiregulin to suppress astrogliosis and promote recovery after ischemic stroke [46]. Conversely, they can also produce chemokines, such as CCL2, CXCL10, and CXCL12, which are involved in leukocyte recruitment into the CNS [47]. During aging, there is an increase in the production of astrocytic CXCL10, which serves as a chemoattractant for peripheral immune cells and aids in T-cell adhesion to endothelial cells [48]. In summary, astrocytes are critical regulators of immune responses in the CNS, as they may promote or dampen neuronal damage and inflammation, depending on the context and stimuli.

2.3. Blood–Brain Barrier Regulation and Maintenance

The BBB is a highly selective semipermeable barrier that restricts the entry of blood cells and plasma components into the brain parenchyma, facilitates the influx of essential nutrients, and mediates the efflux of neurotoxic products. Together, these tasks maintain an optimal environment for neuronal survival and function. The anatomical BBB consists of a continuous monolayer of endothelial cells (ECs) connected by tight junctions (TJ) and adherens junctions (containing claudin, occludin, and zonula occludens proteins). TJ proteins restrict paracellular permeability and also segregate the apical and basal domains of the cell membrane, which enables endothelial polarization [49]. The regulation of the BBB is accomplished by the neurovascular unit (NVU), a multicellular unit that functionally connects the brain and the cerebral vasculature. The NVU is composed of specialized ECs, pericytes, and perivascular astrocytes, whose end-feet sheath all cerebral blood vessels [50].
In addition to the paracellular pathway, several transcellular pathways across the BBB are carefully regulated by the NVU. Due to large surface areas of the lipophilic membranes in ECs, small gaseous molecules, such as O2 and CO2, and small lipid-soluble agents can diffuse freely though the endothelium. Specialized EC transporter proteins, such as glucose transporter 1 (GLUT1) and L-type amino acid transporter 1 (LAT1), supply the brain with glucose and amino acids, respectively. Additional transporters supply the brain with nucleosides, nucleobases, and other substances [51]. Some transporters, such as P-glycoprotein (Pgp), are energy-dependent and act as efflux transporters for neurotoxic molecules [52]. Other proteins, such as insulin and transferrin, are taken up by ECs via receptor-mediated endocytosis and then transported across the BBB in vesicles, in a process called receptor-mediated transcytosis (RMT) [53]. Native plasma proteins, such as albumin, are typically excluded from the healthy adult brain, but can cross the BBB via adsorptive-mediated transcytosis (AMT) under specific conditions [54]. AMT is also vesicle-mediated, but it involves nonspecific binding to the membrane surface charges before internalization and transport through EC cell bodies.
The perivascular end feet of astrocytes show several specialized features, including a high density of K+ transporters and aquaporin (AQP4) water channels, which are involved in ion recycling and brain-volume regulation, respectively [55]. Through a combination of cell–cell interactions and soluble factors, perivascular astrocytes regulate the expression of TJ proteins and directly modify the transport properties of the cerebral endothelium [55][56][57]. Compared with ECs cultured alone, ECs co-cultured with astrocytes or astrocyte-conditioned media were found to exhibit increased TJ formation, transporter expression, and overall improved barrier function [58]. Subsequent studies have identified the molecular mechanisms responsible for the astrocytic regulation of the BBB. For example, the astrocyte secretion of factors such as angiopoietin 1 (ANG1) and sonic hedgehog (SHH) cause ECs to upregulate TJ proteins, thus enhancing barrier tightness [59][60][61].
Beyond BBB regulation, a recent research showed that astrocytes perform a necessary and nonredundant function in adult BBB maintenance [62]. The research used a genetic DTA ablation system to conditionally and selectively ablate astrocytes from the adult mouse brain and observed significant BBBD, indicated by the leakage of cadaverine (~900 Da) and fibrinogen (340 kDa) into the parenchyma. The blood vessels within the regions of astrocyte loss had a lower expression of the TJ protein zonula occludens-1 (ZO-1), while the expression of the endothelial transporter GLUT1 remained undisturbed. BBBD persisted for several weeks following ablation, suggesting a lack of barrier repair [62].
Other roles of astrocytes in BBB function have been studied in the context of disease. For example, the E4 variant of apolipoprotein E (APOE), the main susceptibility gene for AD, leads to accelerated BBBD and cognitive decline in humans and animals [63][64]. APOE is primarily synthesized and secreted in the CNS by astrocytes and is required for BBB formation and maintenance [65]. A recent study used allele-specific knock-in mice with the human E4, E3, and E2 APOE variants and showed that the humanized APOE4, but not APOE2 or APOE3, mice exhibited BBBD, increased matrix metalloproteinases-9 (MMP9), impaired TJs, and reduced the astrocyte end-foot coverage of blood vessels [66]. This is a seminal example of how astrocyte dysfunction can directly lead to BBBD and subsequent neurological disease. Additional mechanisms through which astrocytes contribute to BBBD in aging and disease continue to be explored.


  1. Alzheimer’s Association. Disease Facts and Figures. Alzheimers. Dement. 2021, 17, 327–406.
  2. Herculano-Houzel, S. The Human Brain in Numbers: A Linearly Scaled-up Primate Brain. Front. Hum. Neurosci. 2009, 3, 31.
  3. Vasile, F.; Dossi, E.; Rouach, N. Human Astrocytes: Structure and Functions in the Healthy Brain. Brain Struct. Funct. 2017, 222, 2017–2029.
  4. Sidoryk-Wegrzynowicz, M.; Wegrzynowicz, M.; Lee, E.; Bowman, A.B.; Aschner, M. Role of Astrocytes in Brain Function and Disease. Toxicol. Pathol. 2011, 39, 115–123.
  5. Siracusa, R.; Fusco, R.; Cuzzocrea, S. Astrocytes: Role and Functions in Brain Pathologies. Front. Pharmacol. 2019, 10, 1114.
  6. Batiuk, M.Y.; Martirosyan, A.; Wahis, J.; de Vin, F.; Marneffe, C.; Kusserow, C.; Koeppen, J.; Viana, J.F.; Oliveira, J.F.; Voet, T.; et al. Identification of Region-Specific Astrocyte Subtypes at Single Cell Resolution. Nat. Commun. 2020, 11, 1220.
  7. Pestana, F.; Edwards-Faret, G.; Belgard, T.G.; Martirosyan, A.; Holt, M.G. No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience. Brain Sci. 2020, 10, 168.
  8. Huang, A.Y.S.; Woo, J.; Sardar, D.; Lozzi, B.; Bosquez Huerta, N.A.; Lin, C.C.J.; Felice, D.; Jain, A.; Paulucci-Holthauzen, A.; Deneen, B. Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities. Neuron 2020, 106, 992–1008.e9.
  9. Chaboub, L.S.; Deneen, B. Developmental Origins of Astrocyte Heterogeneity: The Final Frontier of CNS Development. Dev. Neurosci. 2013, 34, 379–388.
  10. Rash, J.E.; Duffy, H.S.; Dudek, F.E.; Bilhartz, B.L.; Whalen, L.R.; Yasumura, T. Grid-Mapped Freeze-Fracture Analysis of Gap Junctions in Gray and White Matter of Adult Rat Central Nervous System, with Evidence for a “panglial Syncytium” That Is Not Coupled to Neurons. J. Comp. Neurol. 1997, 388, 265–292.
  11. Nagy, J.I.; Dudek, F.E.; Rash, J.E. Update on Connexins and Gap Junctions in Neurons and Glia in the Mammalian Nervous System. Brain Res. Rev. 2004, 47, 191–215.
  12. Obermeier, B.; Daneman, R.; Ransohoff, R.M. Development, Maintenance and Disruption of the Blood-Brain Barrier. Nat. Med. 2013, 19, 1584–1596.
  13. Amundson, R.H.; Goderie, S.K.; Kimelberg, H.K. Uptake of Serotonin and Glutamate by Primary Astrocyte Cultures. II. Differences in Cultures Prepared from Different Brain Regions. Glia 1992, 6, 9–18.
  14. Sonnewald, U.; Westergaard, N.; Schousboe, A. Glutamate Transport and Metabolism in Astrocytes. Glia 1997, 21, 56–63.
  15. Kaneko, T.; Shigemoto, R.; Mizuno, N. Metabolism of glutamate and ammonia in astrocyte: An immunocytochemical study. Brain Res. 1988, 457, 160–164.
  16. Hertz, L. Autonomic control of neuronal-astrocytic interactions, regulating metabolic activities, and ion fluxes in the CNS. Brain Res. Bull. 1992, 29, 303–313.
  17. Bellot-Saez, A.; Kékesi, O.; Morley, J.W.; Buskila, Y. Astrocytic modulation of neuronal excitability through K + spatial buffering. Neurosci. Biobehav. Rev. 2017, 77, 87–97.
  18. Walz, W. Role of astrocytes in the clearance of excess extracellular potassium. Neurochem. Int. 2000, 36, 291–300.
  19. Wuttke, W.A.; Walz, W. Sodium- and bicarbonate-independent regulation of intracellular pH in cultured mouse astrocytes. Neurosci. Lett. 1990, 117, 105–110.
  20. Iliff, J.J.; Wang, M.; Liao, Y.; Plogg, B.A.; Peng, W.; Gundersen, G.A.; Benveniste, H.; Vates, G.E.; Deane, R.; Goldman, S.A.; et al. A Paravascular Pathway Facilitates CSF Flow through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Sci. Transl. Med. 2012, 4, 147ra111.
  21. Deane, R.; Bell, R.D.; Sagare, A.; Zlokovic, B.V. Clearance of Amyloid-β Peptide Across the Blood-Brain Barrier: Implication for Therapies in Alzheimers Disease. CNS Neurol. Disord. Drug. Targets 2009, 8, 16–30.
  22. Chung, W.-S.; Allen, N.J.; Eroglu, C. Astrocytes Control Synapse Formation, Function, and Elimination. Cold Spring Harb. Perspect. Biol. 2015, 7, a020370.
  23. Chiu, A.Y.; Espinosa De Los Monteros, A.; Cole, R.A.; Loera, S.; De Vellis, J. Laminin and s-laminin are produced and released by astrocytes, schwann cells, and schwannomas in culture. Glia 1991, 4, 11–24.
  24. Shea, T.B.; Beermann, M.L.; Nixon, R.A. Sequential effects of astroglial-derived factors on neurite outgrowth: Initiation by protease inhibitors and potentiation by extracellular matrix components. J. Neurosci. Res. 1992, 31, 309–317.
  25. Rudge, J.S.; Alderson, R.F.; Pasnikowski, E.; McClain, J.; Ip, N.Y.; Lindsay, R.M. Expression of Ciliary Neurotrophic Factor and the Neurotrophins—Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin 3-in Cultured Rat Hippocampal Astrocytes. Eur. J. Neurosci. 1992, 4, 459–471.
  26. Seil, F.J.; Eckenstein, F.P.; Reier, P.J. Induction of dendritic spine proliferation by an astrocyte secreted factor. Exp. Neurol. 1992, 117, 85–89.
  27. Bukalo, O.; Dityatev, A. Synaptic Cell Adhesion Molecules. Adv. Exp. Med. Biol. 2012, 970, 97–128.
  28. Baldwin, K.T.; Eroglu, C. Molecular mechanisms of astrocyte-induced synaptogenesis. Curr. Opin. Neurobiol. 2017, 45, 113–120.
  29. Christopherson, K.S.; Ullian, E.M.; Stokes, C.C.A.; Mullowney, C.E.; Hell, J.W.; Agah, A.; Lawler, J.; Mosher, D.F.; Bornstein, P.; Barres, B.A. Thrombospondins Are Astrocyte-Secreted Proteins that Promote CNS Synaptogenesis. Cell 2005, 120, 421–433.
  30. Diniz, L.P.; Almeida, J.C.; Tortelli, V.; Lopes, C.V.; Setti-Perdigao, P.; Stipursky, J.; Kahn, S.A.; Romão, L.F.; de Miranda, J.; Alves-Leon, S.V.; et al. Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons. J. Biol. Chem. 2012, 287, 41432–41445.
  31. Diniz, L.P.; Tortelli, V.; Garcia, M.N.; Araújo, A.P.B.; Melo, H.M.; da Silva, G.S.S.; De Felice, F.G.; Alves-Leon, S.V.; de Souza, J.M.; Romão, L.F.; et al. Astrocyte transforming growth factor beta 1 promotes inhibitory synapse formation via CaM kinase II signaling. Glia 2014, 62, 1917–1931.
  32. Kucukdereli, H.; Allen, N.J.; Lee, A.T.; Feng, A.; Ozlu, M.I.; Conatser, L.M.; Chakraborty, C.; Workman, G.; Weaver, M.; Sage, E.H.; et al. Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc. Natl. Acad. Sci. USA 2011, 108, E440–E449.
  33. Risher, W.C.; Patel, S.; Kim, I.H.; Uezu, A.; Bhagat, S.; Wilton, D.K.; Pilaz, L.-J.; Alvarado, J.S.; Calhan, O.Y.; Silver, D.L.; et al. Astrocytes refine cortical connectivity at dendritic spines. eLife 2014, 3, e04047.
  34. Dong, Y.; Benveniste, E.N. Immune function of astrocytes. Glia 2001, 36, 180–190.
  35. Montgomery, D.L. Astrocytes: Form, Functions, and Roles in Disease. Vet. Pathol. 1994, 31, 145–167.
  36. Falsig, J.; Pörzgen, P.; Lund, S.; Schrattenholz, A.; Leist, M. The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function. J. Neurochem. 2006, 96, 893–907.
  37. Priego, N.; Valiente, M. The Potential of Astrocytes as Immune Modulators in Brain Tumors. Front. Immunol. 2019, 10, 1314.
  38. Lee, S.Y.; Chung, W.S. The roles of astrocytic phagocytosis in maintaining homeostasis of brains. J. Pharmacol. Sci. 2020, 145, 223–227.
  39. Lee, J.H.; Kim, J.Y.; Noh, S.; Lee, H.; Lee, S.Y.; Mun, J.Y.; Park, H.; Chung, W.S. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis. Nature 2020, 590, 612–617.
  40. Ransohoff, R.M.; Estes, M.L. Astrocyte Expression of Major Histocompatibility Complex Gene Products in Multiple Sclerosis Brain Tissue Obtained by Stereotactic Biopsy. Arch. Neurol. 1991, 48, 1244–1246.
  41. Rostami, J.; Fotaki, G.; Sirois, J.; Mzezewa, R.; Bergström, J.; Essand, M.; Healy, L.; Erlandsson, A. Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain. J. Neuroinflamm. 2020, 17, 119.
  42. Lazarczyk, M.J.; Kemmler, J.E.; Eyford, B.A.; Short, J.A.; Varghese, M.; Sowa, A.; Dickstein, D.R.; Yuk, F.J.; Puri, R.; Biron, K.E.; et al. Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain. Sci. Rep. 2016, 6, 26199.
  43. Kang, Z.; Altuntas, C.Z.; Gulen, M.F.; Liu, C.; Giltiay, N.; Qin, H.; Liu, L.; Qian, W.; Ransohoff, R.M.; Bergmann, C.; et al. Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis. Immunity 2010, 32, 414–425.
  44. Wheeler, M.A.; Clark, I.C.; Tjon, E.C.; Li, Z.; Zandee, S.E.J.; Couturier, C.P.; Watson, B.R.; Scalisi, G.; Alkwai, S.; Rothhammer, V.; et al. MAFG-driven astrocytes promote CNS inflammation. Nature 2020, 578, 593–599.
  45. You, T.; Bi, Y.; Li, J.; Zhang, M.; Chen, X.; Zhang, K.; Li, J. IL-17 induces reactive astrocytes and up-regulation of vascular endothelial growth factor (VEGF) through JAK/STAT signaling. Sci. Rep. 2017, 7, 41779.
  46. Ito, M.; Komai, K.; Mise-Omata, S.; Iizuka-Koga, M.; Noguchi, Y.; Kondo, T.; Sakai, R.; Matsuo, K.; Nakayama, T.; Yoshie, O.; et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature 2019, 565, 246–250.
  47. Ubogu, E.E.; Cossoy, M.B.; Ransohoff, R.M. The expression and function of chemokines involved in CNS inflammation. Trends Pharmacol. Sci. 2006, 27, 48–55.
  48. Sorensen, E.W.; Lian, J.; Ozga, A.J.; Miyabe, Y.; Ji, S.W.; Bromley, S.K.; Mempel, T.R.; Luster, A.D. CXCL10 stabilizes T cell–brain endothelial cell adhesion leading to the induction of cerebral malaria. JCI Insight 2018, 3, e98911.
  49. Wolburg, H.; Lippoldt, A. Tight junctions of the blood–brain barrier: Development, composition and regulation. Vasc. Pharmacol. 2002, 38, 323–337.
  50. Iadecola, C. The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease. Neuron 2017, 96, 17–42.
  51. Begley, D.J.; Brightman, M.W. Structural and functional aspects of the blood-brain barrier. Prog. Drug Res. 2003, 61, 39–78.
  52. Schinkel, A.H. P-Glycoprotein, a Gatekeeper in the Blood-Brain Barrier. Adv. Drug Deliv. Rev. 1999, 36, 179–194.
  53. Pulgar, V.M. Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges. Front. Neurosci. 2019, 12, 1019.
  54. Hervé, F.; Ghinea, N.; Scherrmann, J.-M. CNS Delivery Via Adsorptive Transcytosis. AAPS J. 2008, 10, 455–472.
  55. Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-Endothelial Interactions at the Blood-Brain Barrier. Nat. Rev. Neurosci. 2006, 7, 41–53.
  56. Michinaga, S.; Koyama, Y. Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage. Int. J. Mol. Sci. 2019, 20, 571.
  57. Abbott, N.J. Astrocyte-Endothelial Interactions and Blood-Brain Barrier Permeability. J. Anat. 2002, 200, 523–534.
  58. Hayashi, Y.; Nomura, M.; Yamagishi, S.I.; Harada, S.I.; Yamashita, J.; Yamamoto, H. Induction of Various Blood-Brain Barrier Properties in Non-Neural Endothelial Cells by Close Apposition to Co-Cultured Astrocytes. Glia 1997, 19, 13–26.
  59. Lee, S.W.; Kim, W.J.; Choi, Y.K.; Song, H.S.; Son, M.J.; Gelman, I.H.; Kim, Y.J.; Kim, K.W. SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat. Med. 2003, 9, 900–906.
  60. Alvarez, J.I.; Dodelet-Devillers, A.; Kebir, H.; Ifergan, I.; Fabre, P.J.; Terouz, S.; Sabbagh, M.; Wosik, K.; Bourbonnière, L.; Bernard, M.; et al. The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence. Science 2011, 334, 1727–1731.
  61. Alvarez, J.I.; Dodelet-Devillers, A.; Kebir, H.; Fabre, P.; Ifergan, I.; Terouz, S.; Sabbagh, M.; Wosik, K.; Bourbonnière, L.; Bernard, M.; et al. The Hedgehog Pathway Promotes Optimal Blood Brain Barrier Functioning. Glia 2013, 61, S190.
  62. Heithoff, B.P.; George, K.K.; Phares, A.N.; Zuidhoek, I.A.; Munoz-Ballester, C.; Robel, S. Astrocytes are necessary for blood–brain barrier maintenance in the adult mouse brain. Glia 2020, 69, 436–472.
  63. Bell, R.D.; Winkler, E.A.; Singh, I.; Sagare, A.P.; Deane, R.; Wu, Z.; Holtzman, D.M.; Betsholtz, C.; Armulik, A.; Sallstrom, J.; et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 2012, 485, 512–516.
  64. Montagne, A.; Nation, D.A.; Sagare, A.P.; Barisano, G.; Sweeney, M.D.; Chakhoyan, A.; Pachicano, M.; Joe, E.; Nelson, A.R.; D’Orazio, L.M.; et al. APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline. Nature 2020, 581, 71–76.
  65. Soto, I.; Graham, L.C.; Richter, H.J.; Simeone, S.N.; Radell, J.E.; Grabowska, W.; Funkhouser, W.K.; Howell, M.C.; Howell, G.R. APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction. PLoS Biol. 2015, 13, e1002279.
  66. Jackson, R.J.; Meltzer, J.C.; Nguyen, H.; Commins, C.; Bennett, R.E.; Hudry, E.; Hyman, B.T. APOE4 derived from astrocytes leads to blood–brain barrier impairment. Brain 2021, awab478.
Subjects: Cell Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : ,
View Times: 431
Entry Collection: Neurodegeneration
Revisions: 2 times (View History)
Update Date: 17 Jun 2022