Chronic cerebral hypoperfusion and plasticity of the posterior cerebral artery following permanent bilateral common carotid artery occlusion

다국어 초록 (Multilingual Abstract)

Vascular dementia (VaD) is a group of heterogeneous diseases with the common feature of cerebral hypoperfusion. To identify key factors contributing to VaD pathophysiology, we performed a detailed comparison of Wistar and Sprague– Dawley (SD) rats subjected to permanent bilateral common carotid artery occlusion (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a reference memory test using a five-radial arm maze with tactile cues. Continuous monitoring of cerebral blood flow (CBF) was performed with a laser Doppler perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for evaluation of the brain vasculature and white matter damage after BCCAo. We found reference memory impairment in Wistar rats, but not in SD rats. Moreover, our LDPI system revealed that Wistar rats had significant hypoperfusion in the brain region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats showed more profound CBF reduction in the forebrain region than did SD rats. Post-mortem analysis of brain vasculature demonstrated greater PCA plasticity at all time points after BCCAo in Wistar rats. Finally, we confirmed white matter rarefaction that was only observed in Wistar rats. Our studies show a comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to severe PCA dolichoectasia, which correlated well with white matter lesion and memory decline.

참고문헌 (Reference)

1 김슬기, "White Matter Damage and Hippocampal Neurodegeneration Induced by Permanent Bilateral Occlusion of Common Carotid Artery in the Rat: Comparison between Wistar and Sprague-Dawley Strain" 대한약리학회 12 (12): 89-94, 2008

2 Smoker WR, "Vertebrobasilar dolichoectasia : clinical-pathologic correlation and review" 7 : 61-72, 1986

3 Román GC, "Vascular cognitive disorder : a new diagnostic category updating vascular cognitive impairment and vascular dementia" 226 : 81-87, 2004

4 Kim SK, "The plasticity of posterior communicating artery influences on the outcome of white matter injury induced by chronic cerebral hypoperfusion in rats" 31 : 245-250, 2009

5 Soria G, "The ins and outs of the BCCAo model for chronic hypoperfusion:a multimodal and longitudinal MRI approach" 8 : e74631-, 2013

6 Lin YW, "The dilemma of treating vertebrobasilar dolichoectasia" 2 : e84-, 2012

7 Choy M, "The chronic vascular and haemodynamic response after permanent bilateral common carotid occlusion in newborn and adult rats" 26 : 1066-1075, 2006

8 Kalaria RN, "Small vessel disease and subcortical vascular dementia" 2 : 1-11, 2006

9 Ma X, "Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia" 8 : 2050-2059, 2013

10 Li WZ, "Protective effect of bilobalide on learning and memory impairment in rats with vascular dementia" 8 : 935-941, 2013

11 Ni J, "Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats" 653 : 231-236, 1994

12 Plassman BL, "Prevalence of dementia in the United States : the aging, demographics, and memory study" 29 : 125-132, 2007

13 Farkas E, "Permanent, bilateral common carotid artery occlusion in the rat : a model for chronic cerebral hypoperfusion-related neurodegenerative diseases" 54 : 162-180, 2007

14 Venkat P, "Models and mechanisms of vascular dementia" 272 : 97-108, 2015

15 Cho KO, "Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion" 83 : 285-291, 2006

16 Otori T, "Long-term measurement of cerebral blood flow and metabolism in a rat chronic hypoperfusion model" 30 : 266-272, 2003

17 Ulrich PT, "Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats" 29 : 2412-2420, 1998

18 Pico F, "Intracranial arterial dolichoectasia and small-vessel disease in stroke patients" 57 : 472-479, 2005

19 Wakita H, "Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion : an immunohistochemical study" 87 : 484-492, 1994

20 Jiwa NS, "Experimental models of vascular dementia and vascular cognitive impairment : a systematic review" 115 : 814-828, 2010

21 Ince B, "Dolichoectasia of the intracranial arteries in patients with first ischemic stroke : a population-based study" 50 : 1694-1698, 1998

22 Storozheva ZI, "Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia" 8 : 1-, 2008

23 Farkas E, "Diazoxide and dimethyl sulphoxide prevent cerebral hypoperfusionrelated learning dysfunction and brain damage after carotid artery occlusion" 1008 : 252-260, 2004

24 Zhang ZH, "Comparison of cognitive performance between two rat models of vascular dementia" 124 : 818-823, 2014

25 Pappas BA, "Chronic reduction of cerebral blood flow in the adult rat : late-emerging CA1 cell loss and memory dysfunction" 708 : 50-58, 1996

26 Sopala M, "Chronic cerebral hypoperfusion in the rat enhances age-related deficits in spatial memory" 108 : 1445-1456, 2001

27 Tanaka K, "Chronic cerebral hypoperfusion disrupts discriminative behavior in acquired-learning rats" 84 : 63-68, 1998

28 Ohta H, "Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats" 79 : 1039-1050, 1997

29 Tsuchiya M, "Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats" 89 : 87-92, 1992

30 Pico F, "Association of small-vessel disease with dilatative arteriopathy of the brain : neuropathologic evidence" 38 : 1197-1202, 2007

31 Liu HX, "Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment" 139 : 169-177, 2005