title: Cortical selective neuronal loss, impaired behavior, and normal magnetic resonance imaging in a new rat model of true transient ischemic attacks.
abstract: OBJECTIVE
  New-definition transient ischemic attacks (TIAs) are frequent but difficult to diagnose because magnetic resonance imaging (MRI)-negative by definition. However, hidden underlying cell damage might be present and account for the reported long-lasting cognitive impairment after TIAs. Most prior rodent models of true TIA targeted the striatum or have not been fully characterized. Here we present the MRI, behavioral, and quantitative cell changes characterizing a new rodent model of true TIA targeting the more behaviorally relevant cerebral cortex.
  
  
  METHODS
  Fifteen-minute distal middle cerebral artery occlusion was performed in 29 spontaneously hypertensive rats allowed to survive for 7 to 60 days. Behavior was assessed serially using both global neurological and fine sensorimotor tests. Diffusion- and T2-weighted MRI was obtained 20 min postreperfusion and again 7 to 60 days later, and then changes in neurons and microglia were quantified across the middle cerebral artery territory using immunohistochemistry.
  
  
  RESULTS
  No MRI changes or pan-necrosis were observed at any time point, but patchy cortical selective neuronal loss affected 28/29 rats, regardless of survival interval, together with topographically congruent microglial activation that gradually declined over time. The Neuroscore was unchanged, but there was marked contralateral sensorimotor impairment, still recovering by day 28.
  
  
  CONCLUSIONS
  Our new rodent model mimicking true cortical TIA is characterized by normal MRI, but consistent cortical selective neuronal loss and microglial activation and long-lasting sensorimotor deficits. By causing selective neuronal loss, TIAs and silent microemboli might affect neuronal reserve, thereby increasing long-term cognitive impairment risk. Selective neuronal loss and microglial activation might represent novel therapeutic targets that could be detectable in vivo after TIAs using appropriate imaging tracers.
authors: From the Stroke Research Group, Department of Clinical Neurosciences (S.E., J.V.E., J.-C.B.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.S., D.J.W.), University of Cambridge; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany (J.V.E.); and INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.).
authors: Sohail
authors: S
authors: Ejaz
authors: From the Stroke Research Group, Department of Clinical Neurosciences (S.E., J.V.E., J.-C.B.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.S., D.J.W.), University of Cambridge; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany (J.V.E.); and INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.).
authors: Julius V
authors: JV
authors: Emmrich
authors: From the Stroke Research Group, Department of Clinical Neurosciences (S.E., J.V.E., J.-C.B.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.S., D.J.W.), University of Cambridge; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany (J.V.E.); and INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.).
authors: Stephen J
authors: SJ
authors: Sawiak
authors: From the Stroke Research Group, Department of Clinical Neurosciences (S.E., J.V.E., J.-C.B.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.S., D.J.W.), University of Cambridge; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany (J.V.E.); and INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.).
authors: David J
authors: DJ
authors: Williamson
authors: From the Stroke Research Group, Department of Clinical Neurosciences (S.E., J.V.E., J.-C.B.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.S., D.J.W.), University of Cambridge; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany (J.V.E.); and INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.). jean-claude.baron@inserm.fr.
authors: Jean-Claude
authors: JC
authors: Baron
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000503:physiopathology; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR
keywords: MCA occlusion; MRI; inflammation; transient ischemic attack