TY - JOUR
T1 - Endovascular middle cerebral artery occlusion in rats as a model for studying vascular dementia
AU - Yang, Shao Hua
AU - Shetty, Ritu A.
AU - Liu, Ran
AU - Sumien, Nathalie
AU - Heinrich, Kevin R.
AU - Rutledge, Margaret
AU - Thangthaeng, Nopporn
AU - Brun-Zinkernagel, Anne Marie
AU - Forster, Michael J.
N1 - Funding Information:
Acknowledgements Supported by National Institutes of Health grants AG10485, AG22550, and a grant from American Heart Association (Texas Affiliate).
PY - 2006/9
Y1 - 2006/9
N2 - Vascular dementia (VaD), incorporating cognitive dysfunction with vascular disease, ranks as the second leading cause of dementia in the United States, yet no effective treatment is currently available. The challenge of defining the pathological substrates of VaD is complicated by the heterogeneous nature of cerebrovascular disease and coexistence of other pathologies, including Alzheimer's disease (AD) types of lesion. The use of rodent models of ischemic stroke may help to elucidate the type of lesions that are responsible for cognitive impairment in humans. Endovascular middle cerebral artery (MCA) occlusion in rats is considered to be a convenient and reliable model of human cerebral ischemia. Both sensorimotor and cognitive dysfunction can be induced in the rat endovascular MCA occlusion model, yet sensorimotor deficits induced by endovascular MCA occlusion may improve with time, whereas data presented in this review suggest that in rats this model can result in a progressive course of cognitive impairment that is consistent with the clinical progression of VaD. Thus far, experimental studies using this model have demonstrated a direct interaction of cerebral ischemic damage and AD-type neuropathologies in the primary ischemic area. Further, coincident to the progressive decline of cognitive function, a delayed neurodegeneration in a remote area, distal to the primary ischemic area, the hippocampus, has been demonstrated in a rat endovascular MCA occlusion model. We argue that this model could be employed to study VaD and provide insight into some of the pathophysiological mechanisms of VaD.
AB - Vascular dementia (VaD), incorporating cognitive dysfunction with vascular disease, ranks as the second leading cause of dementia in the United States, yet no effective treatment is currently available. The challenge of defining the pathological substrates of VaD is complicated by the heterogeneous nature of cerebrovascular disease and coexistence of other pathologies, including Alzheimer's disease (AD) types of lesion. The use of rodent models of ischemic stroke may help to elucidate the type of lesions that are responsible for cognitive impairment in humans. Endovascular middle cerebral artery (MCA) occlusion in rats is considered to be a convenient and reliable model of human cerebral ischemia. Both sensorimotor and cognitive dysfunction can be induced in the rat endovascular MCA occlusion model, yet sensorimotor deficits induced by endovascular MCA occlusion may improve with time, whereas data presented in this review suggest that in rats this model can result in a progressive course of cognitive impairment that is consistent with the clinical progression of VaD. Thus far, experimental studies using this model have demonstrated a direct interaction of cerebral ischemic damage and AD-type neuropathologies in the primary ischemic area. Further, coincident to the progressive decline of cognitive function, a delayed neurodegeneration in a remote area, distal to the primary ischemic area, the hippocampus, has been demonstrated in a rat endovascular MCA occlusion model. We argue that this model could be employed to study VaD and provide insight into some of the pathophysiological mechanisms of VaD.
KW - Alzheimer's disease
KW - Hippocampus
KW - Ischemia
KW - Middle cerebral artery
KW - Stroke
KW - Vascular dementia
UR - http://www.scopus.com/inward/record.url?scp=33845906876&partnerID=8YFLogxK
U2 - 10.1007/s11357-006-9026-4
DO - 10.1007/s11357-006-9026-4
M3 - Article
C2 - 22253496
AN - SCOPUS:33845906876
VL - 28
SP - 297
EP - 307
JO - Age
JF - Age
SN - 0161-9152
IS - 3
ER -