TY - JOUR

T1 - Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke

AU - Ruscher, Karsten

AU - Johannesson, Emelie

AU - Brugiere, Elena

AU - Erickson, Agnes

AU - Rickhag, Karl Mattias

AU - Wieloch, Tadeusz

PY - 2009/11

Y1 - 2009/11

N2 - Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions that differentially improve recovery after occlusion of the middle cerebral artery occlusion (MCAO). We found that after MCAO the ApoE levels increased in the injured hemisphere over a 30 days recovery period. The exception was a proximal narrow peri-infarct rim, in which ApoE was solely localized in S100beta(+)/glial fibrillary acidic protein (GFAP) negative reactive astrocytes at 4 to 7 days of recovery. Enriched housing after MCAO caused a marked decrease in ApoE levels compared with standard housing conditions, particularly in the ApoE/S100beta(+) reactive astrocytes. In addition, the levels of interleukin 1beta were lower in animals housed in an enriched environment. We propose that during the subacute phase after experimental stroke a zone for tissue reorganization with low cellular ApoE levels is formed. We conclude that the strong sensori-motor stimulation provided by enriched housing conditions mitigates the inflammatory response after stroke decreasing the level of ApoE that may contribute to the observed improvement of functional recovery.

AB - Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions that differentially improve recovery after occlusion of the middle cerebral artery occlusion (MCAO). We found that after MCAO the ApoE levels increased in the injured hemisphere over a 30 days recovery period. The exception was a proximal narrow peri-infarct rim, in which ApoE was solely localized in S100beta(+)/glial fibrillary acidic protein (GFAP) negative reactive astrocytes at 4 to 7 days of recovery. Enriched housing after MCAO caused a marked decrease in ApoE levels compared with standard housing conditions, particularly in the ApoE/S100beta(+) reactive astrocytes. In addition, the levels of interleukin 1beta were lower in animals housed in an enriched environment. We propose that during the subacute phase after experimental stroke a zone for tissue reorganization with low cellular ApoE levels is formed. We conclude that the strong sensori-motor stimulation provided by enriched housing conditions mitigates the inflammatory response after stroke decreasing the level of ApoE that may contribute to the observed improvement of functional recovery.

KW - Animals

KW - Apolipoproteins E

KW - Astrocytes

KW - Behavior, Animal

KW - Blotting, Western

KW - Brain

KW - Brain Infarction

KW - Cell Count

KW - Encephalitis

KW - Environment

KW - Enzyme-Linked Immunosorbent Assay

KW - Housing, Animal

KW - Immunohistochemistry

KW - Male

KW - Rats

KW - Rats, Wistar

KW - Stroke

U2 - 10.1038/jcbfm.2009.96

DO - 10.1038/jcbfm.2009.96

M3 - Journal article

C2 - 19623195

VL - 29

SP - 1796

EP - 1805

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 11

ER -