BACKGROUND: The clinical and pathophysiological effects of a chronic reduction of cerebral blood flow in humans are not completely known. We investigated whether rats subjected to bilateral common carotid artery occlusion (bCCA-o) developed focal neurological deficits, gait dysfunction, and working memory alterations. METHODS: Eighteen male Wistar rats were subjected to bCCA-o, 13 were sham-operated. We assessed sensorimotor functions, gait on a 60 cm-long elevated bridge, and working memory (object recognition and Y maze tests) before and 30, 60, and 90 days after surgery. Histological analysis was performed in a subgroup of 10 rats. RESULTS: No rat showed sensorimotor alterations after surgery. Although gait performances of both bCCA-o and sham-operated rats declined over time, the differences reached statistical significance only for the bCCA-o group (mean+/-SE: 26.8+/-5.0; 22.4+/-4.9; 24.5+/-5.5 cm at 30, 60, and 90 days, respectively) in comparison with baseline (52.9+/-5.2 cm; P<0.05). At 60 and 90 days, bCCA-o rats in comparison with sham-operated rats showed decreased performances on object recognition (discrimination index: 0.15+/-0.03 vs. 0.29+/-0.05 at 60 days and 0.10+/-0.04 vs. 0.41+/-0.07 at 90 days; P<0.05) and on Y maze test (alternating rats: 9.9 vs. 85.7% at 60 days and 16.6 vs. 100% at 90 days; P<0.01). In none of the animals were cerebral infarcts detected. Selective neuronal necrosis was observed in the cortex and hippocampus of both bCCA-o and sham-operated rats without any obvious difference. CONCLUSIONS: bCCA-o in the Wistar rat induces persistent and progressive gait and working memory impairment without producing sensorimotor deficit or cerebral infarcts. This model may help to elucidate some physiopathological aspects of neurological impairment associated with states of cerebral chronic ischemia.
BACKGROUND: The clinical and pathophysiological effects of a chronic reduction of cerebral blood flow in humans are not completely known. We investigated whether rats subjected to bilateral common carotid artery occlusion (bCCA-o) developed focal neurological deficits, gait dysfunction, and working memory alterations. METHODS: Eighteen male Wistar rats were subjected to bCCA-o, 13 were sham-operated. We assessed sensorimotor functions, gait on a 60 cm-long elevated bridge, and working memory (object recognition and Y maze tests) before and 30, 60, and 90 days after surgery. Histological analysis was performed in a subgroup of 10 rats. RESULTS: No rat showed sensorimotor alterations after surgery. Although gait performances of both bCCA-o and sham-operated rats declined over time, the differences reached statistical significance only for the bCCA-o group (mean+/-SE: 26.8+/-5.0; 22.4+/-4.9; 24.5+/-5.5 cm at 30, 60, and 90 days, respectively) in comparison with baseline (52.9+/-5.2 cm; P<0.05). At 60 and 90 days, bCCA-o rats in comparison with sham-operated rats showed decreased performances on object recognition (discrimination index: 0.15+/-0.03 vs. 0.29+/-0.05 at 60 days and 0.10+/-0.04 vs. 0.41+/-0.07 at 90 days; P<0.05) and on Y maze test (alternating rats: 9.9 vs. 85.7% at 60 days and 16.6 vs. 100% at 90 days; P<0.01). In none of the animals were cerebral infarcts detected. Selective neuronal necrosis was observed in the cortex and hippocampus of both bCCA-o and sham-operated rats without any obvious difference. CONCLUSIONS: bCCA-o in the Wistar rat induces persistent and progressive gait and working memory impairment without producing sensorimotor deficit or cerebral infarcts. This model may help to elucidate some physiopathological aspects of neurological impairment associated with states of cerebral chronic ischemia.
Authors: Takakuni Maki; Yoon Kyung Choi; Nobukazu Miyamoto; Akihiro Shindo; Anna C Liang; Bum Ju Ahn; Emiri T Mandeville; Seiji Kaji; Kanako Itoh; Ji Hae Seo; Irwin H Gelman; Josephine Lok; Ryosuke Takahashi; Kyu-Won Kim; Eng H Lo; Ken Arai Journal: Stem Cells Date: 2018-01-22 Impact factor: 6.277