Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

被引:25
作者
Aswendt, Markus [1 ,2 ]
Wilhelmsson, Ulrika [3 ]
Wieters, Frederique [1 ,2 ]
Stokowska, Anna [4 ]
Schmitt, Felix Johannes [1 ,2 ]
Pallast, Niklas [1 ,2 ]
de Pablo, Yolanda [3 ]
Mohammed, Lava [3 ]
Hoehn, Mathias [5 ]
Pekna, Marcela [4 ]
Pekny, Milos [3 ,6 ,7 ]
机构
[1] Univ Cologne, Fac Med, Dept Neurol, Cologne, Germany
[2] Univ Cologne, Univ Hosp Cologne, Cologne, Germany
[3] Univ Gothenburg, Sahlgrenska Acad, Lab Astrocyte Biol & CNS Regenerat, Ctr Brain Repair,Dept Clin Neurosci,Inst Neurosci, Gothenburg, Sweden
[4] Univ Gothenburg, Sahlgrenska Acad, Lab Regenerat Neuroirumunol, Ctr Brain Repair,Dept Clin Neurosci,Inst Neurosci, Gothenburg, Sweden
[5] Res Ctr Juelich, Inst Neurosci & Med INM 3, Cognit Neurosci, Julich, Germany
[6] Univ Newcastle, Newcastle, NSW, Australia
[7] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia
基金
瑞典研究理事会; 英国医学研究理事会;
关键词
Stroke; Recovery; Reactive gliosis; Intermediate filaments (nanofilaments); MRI; Functional connectivity; FIBRILLARY ACIDIC PROTEIN; FUNCTIONAL RECOVERY; MICE DEFICIENT; INTERMEDIATE-FILAMENTS; VIMENTIN; GFAP; NEUROGENESIS; CONNECTIVITY; HIPPOCAMPUS; ACTIVATION;
D O I
10.1016/j.pneurobio.2021.102199
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP(-/-)Vim(-/-)). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP(-/-)Vim(-/-) mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes modulate recovery-promoting plasticity responses after ischemic stroke.
引用
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页数:13
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