Inflammatory Response and Chemokine Expression in the White Matter Corpus Callosum and Gray Matter Cortex Region During Cuprizone-Induced Demyelination

被引:108
作者
Buschmann, J. P. [1 ]
Berger, K. [1 ]
Awad, H. [1 ]
Clarner, T. [1 ]
Beyer, C. [1 ]
Kipp, M. [1 ,2 ]
机构
[1] Rhein Westfal TH Aachen, Inst Neuroanat, Fac Med, D-52074 Aachen, Germany
[2] Vrije Univ Amsterdam, Dept Pathol, Med Ctr, NL-1081 HV Amsterdam, Netherlands
关键词
Cuprizone; CNS; Inflammation; Chemokines; Demyelination; Multiple sclerosis; MULTIPLE-SCLEROSIS LESIONS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; CORTICAL DEMYELINATION; CHEMOTACTIC CYTOKINES; LEWIS RATS; DIFFERENTIATION; ASTROCYTES; PATHOLOGY;
D O I
10.1007/s12031-012-9773-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Brain inflammation plays a central role in multiple sclerosis (MS). Besides lymphocytes, the astroglia and microglia mainly contribute to the cellular composition of the inflammatory infiltrate in MS lesions. Several studies were able to demonstrate that cortical lesions are characterized by lower levels of inflammatory cells among activated microglia/macrophages. The underlying mechanisms for this difference, however, remain to be clarified. In the current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter. Cellular parameters were related to the expression profiles of the chemokines Ccl2 and Ccl3. We are clearly able to demonstrate that both regions are characterized by early oligodendrocyte stress/apoptosis with concomitant microglia activation and delayed astrocytosis. The extent of microgliosis/astrocytosis appeared to be greater in the subcortical white matter tract corpus callosum compared to the gray matter cortex region. The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter.
引用
收藏
页码:66 / 76
页数:11
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