title: Lasting pure-motor deficits after focal posterior internal capsule white-matter infarcts in rats.
abstract: Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3 mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (~1 mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury.
authors: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Francesco
authors: F
authors: Blasi
authors: 1] Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA [2] Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Michael J
authors: MJ
authors: Whalen
authors: 1] Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA [2] Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Cenk
authors: C
authors: Ayata
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000008:administration & dosage; D020772:Internal Capsule / Q000473:pathology*; D008297:Male; D009048:Motor Skills; D009186:Myelin Sheath / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
chemical_list: D019332:Endothelin-1
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