The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit

Nat Neurosci. 2013 Jan;16(1):55-63. doi: 10.1038/nn.3278. Epub 2012 Dec 16.


Microinfarctions are present in the aged and injured human brain. Their clinical relevance is controversial, with postulated sequelae ranging from cognitive sparing to vascular dementia. To address the consequences of microinfarcts, we used controlled optical methods to create occlusions of individual penetrating arterioles or venules in rat cortex. Single microinfarcts, targeted to encompass all or part of a cortical column, impaired performance in a macrovibrissa-based behavioral task. Furthermore, the targeting of multiple vessels resulted in tissue damage that coalesced across cortex, even though the intervening penetrating vessels were acutely patent. Post-occlusion administration of memantine, a glutamate receptor antagonist that reduces cognitive decline in Alzheimer's disease, ameliorated tissue damage and perceptual deficits. Collectively, these data imply that microinfarcts likely contribute to cognitive decline. Strategies that have received limited success in the treatment of ischemic injury, which include therapeutics against excitotoxicity, may be successful against the progressive nature of vascular dementia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Infarction / etiology*
  • Brain Infarction / pathology
  • Brain Infarction / physiopathology
  • Brain Mapping*
  • Calcium / metabolism
  • Cognition Disorders / etiology*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology
  • Dizocilpine Maleate / therapeutic use
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Imaging, Three-Dimensional
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology*
  • Male
  • Memantine / therapeutic use
  • Microscopy, Confocal
  • Microvessels / pathology*
  • Models, Biological
  • Neural Pathways / physiology
  • Neuroprotective Agents / therapeutic use
  • Phosphopyruvate Hydratase / metabolism
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Somatosensory Cortex / drug effects
  • Somatosensory Cortex / physiopathology
  • Vibrissae / innervation


  • Glial Fibrillary Acidic Protein
  • Neuroprotective Agents
  • Dizocilpine Maleate
  • Phosphopyruvate Hydratase
  • Calcium
  • Memantine