Long-term functional consequences of transient occlusion of the middle cerebral artery in rats:

Karhunen, Heli; Pitkänen, Asla; Virtanen, Tiina; Gureviciene, Irina; Pussinen, Raimo; Ylinen, Aarne; Sivenius, Juhani; Nissinen, Jari; Jolkkonen, Jukka

doi:10.1016/s0920-1211(03)00034-2

Cited by 51 publications

(12 citation statements)

References 29 publications

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“…Sensorimotor impairment has been extensive studied in rats after MCAO. Spontaneous partial or complete recovery of sensorimotor function has been frequently reported over time after ischemic stroke in this model (DeVries et al, 2001; Karhunen et al, 2003; Markgraf et al, 1994; Markgraf et al, 1997; Roof et al, 2001; Yonemori et al, 1999). On the other hand, a progressive cognitive function impairment was indicated (Yang et al, 2006).…”

Section: Discussionmentioning

confidence: 67%

“…The experimental protocols and indices of cognitive performance used in previous studies of experimental stroke injury have varied considerably, and this may account for significant inconsistency in the reported outcomes (Bingham et al, 2012). However, deficient performance of rats in the Morris water maze and other spatial tasks, which is a reliable outcome following hippocampal damage (Winocur and Moscovitch, 1990), would appear to be a consistent outcome over time after MCAO (Bingham et al, 2012; DeVries et al, 2001; Karhunen et al, 2003). In the present study, rats showed a progressive impairment of spatial learning and memory after ischemic stroke, which might be best described as initially a delayed acquisition, followed later by an impaired rate of learning and impaired retention which could be detected in the absence of visual or sensorimotor impairment.…”

Section: Discussionmentioning

confidence: 99%

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Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Huang

Shetty

et al. 2013

Neurobiology of Disease

103

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Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague-Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30 days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30 days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30 days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both sides of the hippocampus was reduced at 30 days after stroke. This LTP impairment was prevented by blocking GABAA receptors. In addition, ERK activity was significantly reduced in both sides of the hippocampus. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Huang

Shetty

et al. 2013

Neurobiology of Disease

103

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“…Damage or destruction of the hippocampus is followed by cognitive deficit, memory disorders (in humans) [6], and impairment of learning (in rats) [11]. Impairment of conditioned-reflex activity and memory was found in rats with carotid artery occlusion [8,12].…”

Section: Resultsmentioning

confidence: 99%

Multiparameter Analysis of EEG in Old Wistar Rats after Bilateral Carotid Artery Ligation

2009

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We showed that 302 of 840 EEG parameters in old Wistar rats significantly change 3 h after bilateral carotid artery ligation. All animals (n=7) died 250+/-47 min after ligation. EEG power spectra had signs of suppression (increased d-activity, decreased t-activity, and increased low-frequency alpha-activity) or activation of CNS (decreased high-frequency alpha-activity and paroxysmal increase in beta-activity). The coherence, synchrony, and entropy of potentials were reduced in the majority of brain regions. This method and scheme of experiments are suitable for the search and study of anti-stroke drugs.

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“…Cognitive deficits in water maze tasks would be confounded by serious sensorimotor deficits in the experimental stroke model, such as MCAO 15,16. In the study, photothrombosis model, which causes minor sensorimotor deficits and long-term cognitive deficits, appears suitable for the preclinical cognitive evaluation of novel candidate drugs on ischemia stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Two commonly used animal models of ischemic stroke, middle cerebral artery occlusion (MCAO) model and the cortical photothrombotic model, are both associated with deficits in sensorimotor and cognitive function 13,14. In previous studies,15,16 the cognitive evolution in Morris Water Maze (MWM) tests after the MCAO surgery are confounded, as it induced severe sensorimotor deficits. In contrast, the model of photothrombosis has the ability to control the size of infarcts in explicit brain regions with distinct functions, which show significant changes in some stroke patients,17 such as the frontal cortex.…”

Section: Introductionmentioning

confidence: 99%

Protective efficacy of a single salvianolic acid A treatment on photothrombosis-induced sustained spatial memory impairments

Chun-xiang¹,

Zhou²,

Yang³

et al. 2017

NDT

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With respect to the high burden of ischemic stroke and the absence of pharmacological treatment for promoting rehabilitation, promising candidates with specific effects on long-term functional recovery are highly desired. Candidates need reasonable experimental paradigms to evaluate the long-term functional outcome focused on ischemia-induced sensorimotor and memory deficits. “Danshen”, a traditional Chinese herb, has long been used to treat coronary and cerebral vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major active ingredients of Danshen, was demonstrated to be effective in protecting against cerebral ischemic injury. Here, employing an experimental stroke model induced by photothrombosis in the unilateral frontal cortex of rats, we investigated whether SAA has long-term protective effects on ischemia-induced sensorimotor and memory deficits in our behavioral tests. The results indicated that a single SAA treatment improved the cortical ischemia-induced sensorimotor deficits during 15 days’ cylinder test period, and alleviated ischemia-induced sustained spatial memory impairments during the 2 months’ dependent Morris Water Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not show any changes compared with sham group in other behavioral tests including rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze tests, treadmill tests and forced swimming tests. The results reveal that the cognitive deficits are not the results of animal’s anxiety or confounding motor impairments. Overall, the present paradigm appears suitable for the preclinical evaluation of the long-term effects of pharmacological treatments on ischemic stroke. Meanwhile, SAA might have therapeutic potential for the treatment of memory deficits associated with ischemic stroke.

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Long-term functional consequences of transient occlusion of the middle cerebral artery in rats:

Cited by 51 publications

References 29 publications

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Multiparameter Analysis of EEG in Old Wistar Rats after Bilateral Carotid Artery Ligation

Protective efficacy of a single salvianolic acid A treatment on photothrombosis-induced sustained spatial memory impairments

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