Rodent Models of Vascular Cognitive Impairment
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SI: CHALLENGES AND CONTROVERSIES IN TRANSLATIONAL STROKE RESEARCH
Rodent Models of Vascular Cognitive Impairment Yi Yang 1 & Shihoko Kimura-Ohba 1 & Jeffrey Thompson 1 & Gary A. Rosenberg 1,2,3
Received: 2 February 2016 / Revised: 9 July 2016 / Accepted: 19 July 2016 # Springer Science+Business Media New York 2016
Abstract Vascular cognitive impairment dementia (VCID), which is an increasingly important cause of dementia in the elderly, lacks effective treatments. Many different types of vascular disease are included under the diagnosis of VCID, including large vessel disease with multiple strokes and small vessel disease with lacunar infarcts and white matter disease. Animal models have been developed to study the multiple forms of VCID. Because of its progressive course, small vessel disease (SVD) is thought to be the optimal form of VCID for treatment. One theory is that the pathophysiology involves hypoxic hypoperfusion resulting in injury to the white matter and neuronal death. Bilateral occlusion of the common carotid arteries (BCAO) in a normotensive rat, which reduces cerebral blood flow, induces hypoxia with white matter damage; this model has been used to test drugs to block the injury. Another model is the spontaneously hypertensive/stroke prone rat (SHR/SP). Hypertension leads to small vessel disease resulting in progressive damage to the white matter, cortex, and hippocampus. Bilateral carotid artery stenosis (BCAS) with coils or ameroid constrictors produces a slower development of changes than BCAO, avoiding the acute ischemia. A few studies have been done with the two-clip, two-vessel occlusion renal model for induction of hypertension. There are benefits and drawbacks to each of these models with the
* Gary A. Rosenberg [email protected] 1
Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
2
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
3
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
model selected depending on the type of vascular damage that is to be studied. This review describes the most commonly used models, and the drugs that have been used to reduce the damage. Keywords Vascular cognitive impairment . Neuroinflammation . Spontaneously . Hypertensive rats . Matrix metalloproteinases
Introduction Vascular disease has been identified as an increasingly important cause of dementia, making it imperative that treatments be developed for the growing number of patients with dementia related to vascular disease [1, 2]. Vascular cognitive impairment dementia (VCID) is the term suggested for all forms of dementia related to vascular disease [3]. The term includes multiple forms of stroke, which can be separated into large vessel and small vessel disease (SVD). Multiple pathophysiologies result in a heterogeneous patient population that greatly complicates treatment trials, and makes it necessary to stratif
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