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The Role of Glia in Excitotoxicity and Stroke

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Neurons are highly integrated both anatomically and metabolically with glial cells, and thus glial cells have a major influence on neuronal survival in ischemia and excitotoxicity. Of the three types of glia in the central nervous system—astrocytes, oligodendrocytes, and microglia—the role of astrocytes in excitotoxicity and ischemia has been best characterized. Under different settings, astrocytes can both limit or contribute to excitotoxic neuronal death. Astrocytes also influence oxidative neuronal injury and contribute to neuronal demise through secretion of nitric oxide and cytokines. Microglia, the resident macrophages of the CNS, can also have both deleterious and salutary effects on neuronal survival. Activated microglia can kill neurons, but on the other hand normal microglial function is probably required for brain remodeling after injury. Interactions between microglia and astrocytes engender an additional layer of complexity to these post‐ischemic processes.

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Abbreviations

AA:

arachidonic acid

Ala:

alanine

AMPA:

α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid

AMPA/KAR:

AMPA/kainate receptor

APP:

amyloid precursor protein

ATP:

adenosine triphosphate

BCAA:

branched amino acid

BDNF:

brain‐derived neurotrophic factor

bFGF:

basic fibroblast growth factor

CDNF:

ciliary neurotrophic factor

COX‐2:

cyclooxygenase

cPLA2:

cytoplasmic phospholipase A

DNA:

deoxyribonucleic acid

iNOS:

inducible nitric oxide synthase

GDNF:

glial cell‐derived neurotrophic factor

Glu:

glutamate

Gln:

glutamine

CNS:

central nervous system

EAAT:

excitatory amino acid transporter

GABA:

gamma‐aminobutyric acid

GLAST:

glial glutamate and aspartate transporter

GLT‐1:

glial glutamate transporter

GlyT:

glycine transporter

GM‐CSF:

granulocyte‐magrophage colony‐stimulating factor

GSH:

glutathione

HIF‐1:

hypoxia‐inducible factor‐1

HO‐1:

heme oxygenase ‐1

ICAM‐1:

intracellular adhesion molecule‐1

ICE:

interleukin‐1 converting enzyme

IGF‐I:

insulin growth factor I

IL:

interleukin

JAK‐2:

janus tyrosine kinase‐2

αKG:

α‐ketoglutarate

KIC:

α‐ketoisocaproate

MAPK:

mitogen‐activated protein kinase

M‐CSF:

macrophage colony‐stimulating factor

MHC:

major histocompatibility complex

MIP‐1:

macrophage inflammatory protein‐1

MMP:

matrix metalloproteases

NF‐κB:

nuclear factor‐kappaB

NGF:

nerve growth factor

NMDA:

N‐methyl‐D‐aspartate

NT‐3:

neurotrophin‐3

PA:

plasminogen activator

PARP‐1:

poly(ADP‐ribose) polymerase‐1

PDGF:

platelet derived growth factor

PG:

prostaglandin

PKC:

protein kinase C

PYK2:

proline‐rich protein tyrosine kinase

Pyr:

puryvate

RANTES:

regulation on activation normal T‐cell expressed and secreted

SAT:

sodium‐coupled amino acid transporter

TCA:

tricarboxylic acid cycle

TGF:

transforming growth factor

TIMP:

tissue‐specific inhibitor of metalloproteinase

TNF:

tumor necrosis factor

t‐PA:

tissue‐specific plasminogen activator

u‐PA:

urokinase‐plasminogen activator

VEGF:

vascular endothelial growth factor

VSOAC:

volume‐sensitive organic anion channel

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Authors
  1. T. M. Kauppinen
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  2. R. A. Swanson
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, 94305-5487, USA

    Pak H. Chan (Director Neurosurgical Labouratories) (Director Neurosurgical Labouratories)

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Kauppinen, T.M., Swanson, R.A. (2007). The Role of Glia in Excitotoxicity and Stroke. In: Lajtha, A., Chan, P.H. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30383-3_9

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