Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat

2003 ◽  
Vol 992 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Hideaki Wakita ◽  
Hidekazu Tomimoto ◽  
Ichiro Akiguchi ◽  
Jin-Xi Lin ◽  
Masafumi Ihara ◽  
...  
Keyword(s):  
White Matter ◽  
Phosphodiesterase Inhibitor ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
White Matter Damage

scholarly journals Comprehensive Evaluation of White Matter Damage and Neuron Death and Whole-Transcriptome Analysis of Rats With Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 13 ◽  
Author(s):  
Wenxian Li ◽  
Di Wei ◽  
Jianye Liang ◽  
Xiaomei Xie ◽  
Kangping Song ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Neuronal Death ◽  
Chronic Cerebral Hypoperfusion ◽  
Differentially Expressed ◽  
Cerebral Hypoperfusion ◽  
Neuron Death ◽  
White Matter Damage ◽  
Morris Water Maze Task ◽  
Whole Transcriptome

Background/AimsChronic cerebral hypoperfusion (CCH) is induced by chronic deficit of brain perfusion, contributes to a persistent or progressive cognitive dysfunction, which is characterized by diverse neuropathological manifestations. There are currently no effective medications available. White matter damage (WMD) and cortical neuron death may be caused by CCH, which are related to cognitive impairment, while the underlying molecular mechanisms remain unclear. In the study, a database of the transcriptome level was built to determine potential biomarkers in cortex of CCH.MethodsCCH was induced in male Sprague-Dawley rats by permanent occlusion of the bilateral common carotid arteries. Rats were randomly divided into three groups: Sham-operated group (n = 24), the 4th and 8th week of CCH groups (total = 56, n = 28 for each group). Cognitive function was evaluated using the Morris water maze task. WMD and neuron damage were detected using diffusion tensor imaging and histological analysis, respectively. Western blotting analysis of various markers was used to examine neuronal death. Whole-transcriptome microarray was performed to assess mRNA, circRNA, and lncRNA expression profiles at 4th and 8th weeks after CCH. Diversified bioinformatic tools were performed to analyze and predict the key biological processes and signaling pathways of differentially expressed RNAs and co-expressed potential target genes. Co-expression networks of mRNA–circRNA–miRNA and lncRNA–mRNA were constructed.ResultsCompared to the sham group, cognitive impairment, disintegration of white matter, blood-brain barrier damage and neuron death were induced by CCH. Neuron death including apoptosis and necroptosis might occur in the cortex of CCH. We constructed the regulatory networks of whole-transcriptomic including differentially expressed mRNAs, circRNAs, and lncRNAs, and related biological functions and pathways involved in neurological disease, cell death and survival, energy and metabolism, et al. Our results also indicated that Cyr61 mRNA may play a role in the CCH-related cortical neuronal death.ConclusionWMD and cortical neuronal death are worthy of attention in the pathogenesis of CCH. Additionally, the present results provide potential evidence at the whole-transcription level for CCH, offering candidate biomarkers and therapeutic targets.

Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion

2006 ◽  
Vol 83 (2) ◽  
pp. 285-291 ◽  
Author(s):  
Kyung-Ok Cho ◽  
Hyen O. La ◽  
Young-Jin Cho ◽  
Ki-Wug Sung ◽  
Seong Y. Kim
Keyword(s):  
White Matter ◽  
Rat Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
White Matter Damage

scholarly journals Cilostazol Protects Against Brain White Matter Damage and Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion

Stroke ◽  
2006 ◽  
Vol 37 (6) ◽  
pp. 1539-1545 ◽  
Author(s):  
Terubumi Watanabe ◽  
Ning Zhang ◽  
Meizi Liu ◽  
Ryota Tanaka ◽  
Yoshikuni Mizuno ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Rat Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
White Matter Damage ◽  
Brain White Matter

scholarly journals Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Liu ◽  
Guifeng Zhao ◽  
Ling Jin ◽  
Jingping Shi
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Western Blotting ◽  
Blood Supply ◽  
Sham Group ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Morris Water Maze Test ◽  
White Matter Damage

Normal brain function requires steady blood supply to maintain stable energy state. When blood supply to the brain becomes suboptimal for a long period of time, chronic cerebral hypoperfusion (CCH) and a variety of brain changes may occur. CCH causes white matter injury and cognitive impairment. The present study investigated the effect of nicotinamide (NAM) on CCH-induced cognitive impairment and white matter damage in mice. Male C57Bl/6J mice aged 10–12 weeks (mean age = 11 ± 1 weeks) and weighing 24 - 29 g (mean weight = 26.5 ± 2.5 g) were randomly assigned to three groups (eight mice/group): sham group, CCH group and NAM group. Chronic cerebral hypoperfusion (CCH) was induced using standard methods. The treatment group mice received intraperitoneal injection of NAM at a dose of 200 mg/kg body weight (bwt) daily for 30 days. Learning, memory, anxiety, and depression-like behaviors were measured using Morris water maze test (MWMT), open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), respectively. White matter damage and remodeling were determined via histological/ immunohistochemical analyses, and western blotting, respectively. The results showed that the time spent in target quadrant, number of crossings and escape latency were significantly lower in CCH group than in sham group, but they were significantly increased by NAM (p < 0.05). Mice in NAM group moved significantly faster and covered longer distances, when compared with those in CCH group (p < 0.05). The percentage of time spent in open arms and the number of entries to the open arms were significantly lower in CCH group than in NAM group (p < 0.05). Moreover, anhedonia and histologic scores (index of myelin injury) were significantly higher in CCH group than in sham group, but they were significantly reduced by NAM (p < 0.05). The results of immunohistochemical staining and Western blotting showed that the protein expressions of 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and synaptophysin were significantly downregulated in CCH group, relative to sham group, but they were significantly upregulated by NAM (p < 0.05). These results indicate that NAM improves cognitive function in mice with CCH.

Sign in / Sign up

Export Citation Format

Share Document