In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis.
Reactive astrogliosis is a prominent pathological feature of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. It is characterized by hypertrophy of astrocytes with increased content of glial fibrillary acidic protein (GFAP.) Studies of reactive astrocytes in acute experimental autoimmune encephalomyelitis have been complicated by the observation that the diffuse increase in GFAP immunohistochemical staining at the onset of central nervous system inflammation does not parallel the gradual increase in GFAP content probably because tissue edema enhances GFAP immunostaining. To characterize changes in GFAP expression, we performed in situ hybridization at 3- to 7-day intervals during the course of acute murine experimental autoimmune encephalomyelitis. We found a biphasic course of GFAP expression: an early phase of astrocyte reaction surrounding perivascular inflammatory cuffs and submeningeal infiltrates at the onset of central nervous system inflammation and clinical disease and a later phase of increased GFAP mRNA expression in regions of demyelination during resolution of inflammation and clinical improvement. IP-10, a member of a family of proinflammatory chemoattractant cytokines called chemokines, was expressed by astrocytes in a similar distribution as those expressing increased GFAP mRNA in the early phase of inflammation but was no detected in astrocytes in the later phase of activation. These results indicate that location and function of reactive astrocytes may vary during the course of immune-mediated demyelination.
Tani
M
M
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195, USA
Glabinski
A R
AR
Tuohy
V K
VK
Stoler
M H
MH
Estes
M L
ML
Ransohoff
R M
RM
D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger