Manganese-enhanced MRI of brain plasticity in relation to functional recovery after experimental stroke.
Restoration of function after stroke may be associated with structural remodeling of neuronal connections outside the infarcted area. However, the spatiotemporal profile of poststroke alterations in neuroanatomical connectivity in relation to functional recovery is still largely unknown. We performed in vivo magnetic resonance imaging (MRI)-based neuronal tract tracing with manganese in combination with immunohistochemical detection of the neuronal tracer wheat-germ agglutinin horseradish peroxidase (WGA-HRP), to assess changes in intra- and interhemispheric sensorimotor network connections from 2 to 10 weeks after unilateral stroke in rats. In addition, functional recovery was measured by repetitive behavioral testing. Four days after tracer injection in perilesional sensorimotor cortex, manganese enhancement and WGA-HRP staining were decreased in subcortical areas of the ipsilateral sensorimotor network at 2 weeks after stroke, which was restored at later time points. At 4 to 10 weeks after stroke, we detected significantly increased manganese enhancement in the contralateral hemisphere. Behaviorally, sensorimotor functions were initially disturbed but subsequently recovered and plateaued 17 days after stroke. This study shows that manganese-enhanced MRI can provide unique in vivo information on the spatiotemporal pattern of neuroanatomical plasticity after stroke. Our data suggest that the plateau stage of functional recovery is associated with restoration of ipsilateral sensorimotor pathways and enhanced interhemispheric connectivity.
van der Zijden
Jet P
JP
Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
Bouts
Mark Jrj
MJ
Wu
Ona
O
Roeling
Tom Ap
TA
Bleys
Ronald Law
RL
van der Toorn
Annette
A
Dijkhuizen
Rick M
RM
D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D009434:Neural Pathways / Q000166:cytology*; D009473:Neuronal Plasticity / Q000502:physiology*; D011856:Radiographic Image Enhancement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D008345:Manganese