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Glutamate transporter EAAT2 expression is up‐regulated in reactive astrocytes in human periventricular leukomalacia
Author(s) -
Desilva Tara M.,
Billiards Saraid S.,
Borenstein Natalia S.,
Trachtenberg Felicia L.,
Volpe Joseph J.,
Kinney Hannah C.,
Rosenberg Paul A.
Publication year - 2008
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21667
Subject(s) - periventricular leukomalacia , excitotoxicity , glutamate receptor , astrocyte , white matter , biology , pathology , oligodendrocyte , immunocytochemistry , western blot , neuroscience , medicine , central nervous system , endocrinology , magnetic resonance imaging , biochemistry , myelin , genetics , pregnancy , receptor , radiology , gene , gestational age
The major neuropathological correlate of cerebral palsy in premature infants is periventricular leukomalacia (PVL), a disorder of the immature cerebral white matter. Cerebral ischemia leading to excitotoxicity is thought to be important in the pathogenesis of this disorder, implying a critical role for glutamate transporters, the major determinants of extracellular glutamate concentration. Previously, we found that EAAT2 expression is limited primarily to premyelinating oligodendrocytes early in development and is rarely observed in astrocytes until >40 weeks. In this study, we analyzed the expression of EAAT2 in cerebral white matter from PVL and control cases. Western blot analysis suggested an up‐regulation of EAAT2 in PVL compared with control cases. Single‐ and double‐label immunocytochemistry showed a significantly higher percentage of EAAT2‐immunopositive astrocytes in PVL (51.8% ± 5.6%) compared with control white matter (21.4% ± 5.6%; P = 0.004). Macrophages in the necrotic foci in PVL also expressed EAAT2. Premyelinating oligodendrocytes in both PVL and control cases expressed EAAT2, without qualitative difference in expression. The previously unrecognized up‐regulation of EAAT2 in reactive astrocytes and its presence in macrophages in PVL reported here may reflect a response to either hypoxic‐ischemic injury or inflammation. J. Comp. Neurol. 508:238–248, 2008. © 2008 Wiley‐Liss, Inc.