scholarly journals Chronic treatment of 4-phenylbutyric acid ameliorates cognitive impairment after focal cerebral ischemia/ reperfusion injury in rats

2021 ◽  
Vol 64 ◽  
pp. 188-194
Author(s):  
Kakarla Ramakrishna ◽  
Krishnamoorthy Srinivasan ◽  
Shyam Sunder Sharma
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Motor Deficits ◽  
Avoidance Task ◽  
Neurological Score ◽  
Y Maze ◽  
Phenylbutyric Acid

Objectives: Stroke, apart from causing physical disabilities, it also often leads to cognitive impairment in patients. At present, there is no effective drug available for the treatment of post-stroke cognitive impairment. The present study was undertaken to evaluate the ameliorative effect of 4-Phenylbutyric acid (PBA) against cognitive and memory deficits due to focal cerebral ischemia/reperfusion (I/R) in rats. Materials and Methods: Focal cerebral I/R injury was achieved by the middle cerebral artery occlusion (MCAO) method. PBA (100 and 300 mg/kg, i.p.) was administered once daily for 2 weeks. The neurological score was counted to evaluate the severity of neurological motor deficits. The cognitive functions, including learning and memory, were assessed using various paradigms such as Y-maze, passive avoidance task and Morris water maze. Results: The chronic treatment of PBA (100 and 300 mg/kg, i.p.) dose-dependently improved the neurological motor deficits as shown by significant decrease in neurological score in MCAO-treated rats. Besides, PBA (100 and 300 mg/kg, i.p.) treatment markedly improved working memory as shown by significant increase in the relative percentage alternations compared to untreated control MCAO rats in Y-maze. PBA also significantly decreased the transfer latency in the acquisition trial and increased in probe trial in passive avoidance task suggesting an improvement in learning and memory in MCAO rats. There was also a significant improvement in spatial learning and memory, as evidenced by the reduced escape latency in acquisition trial and the increased number of entries into the platform zone, time spent in the platform quadrant and track plot in probe trial PBA-treated MCAO rats during Morris water maze task. Conclusion: This study, thus, demonstrates the potential of PBA in ameliorating cognitive dysfunctions in focal cerebral ischemia. Since PBA is already available for the treatment of urea cycle disorders, it may also be investigated for repurposing its use in the treatment of post-stroke cognitive impairment.

scholarly journals Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094619
Author(s):  
Liru Li ◽  
Jie Huang
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion ◽  
Y Maze

Although rapamycin can attenuate cerebral ischemia/reperfusion (I/R) injury, the potential roles of rapamycin on cerebral I/R injury remain largely controversial. The present work aims to evaluate underlying molecular mechanisms of rapamycin pretreatment on I/R injury. In total, 34 Sprague-Dawley rats were randomly grouped to 3 groups: sham group (n = 2), vehicle group (n = 16), and rapamycin-pretreatment group (n = 16). Before the focal cerebral ischemia was induced, those rats in the pretreatment group were intraperitoneally injected rapamycin (1 mg/kg body) for 20 hours, while rats in the vehicle group received same-volume saline. Then, rats in these 2 groups received focal cerebral ischemia for 3 and 6 hours, respectively (n = 8 in each group), which was followed by the application of reperfusion for 4, 24, 72 hours, and 1 week (n = 2 in each group). The results showed that the rapamycin pretreatment improved the memory functions of rats after I/R injury, which was evaluated using a Y-maze test. Rapamycin pretreatment significantly reduced the size of triphenyltetrazolium chloride infarction and decreased the expression of I/R injury markers. Moreover, the expression of LC-3 and NFκB was also significantly reduced after rapamycin pretreatment. Taken together, rapamycin pretreatment may alleviate cerebral I/R injury partly through inhibiting autophagic activities and NFκB pathways in rats.

scholarly journals Electroacupuncture Pretreatment Prevents Cognitive Impairment Induced by Cerebral Ischemia–Reperfusion via Adenosine A1 Receptors in Rats

2021 ◽  
Vol 13 ◽  
Author(s):  
Yiyi Shi ◽  
Qinxue Dai ◽  
Binbin Ji ◽  
Luping Huang ◽  
Xiuxiu Zhuang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Receptor Protein ◽  
Short Interfering Rna ◽  
Sprague Dawley ◽  
Left Lateral Ventricle ◽  
A1 Receptor ◽  
Interfering Rna

A previous study has demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. In the present study, we investigated whether adenosine receptor 1 (A1 R) is involved in EA pretreatment-induced cognitive impairment after focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min in male Sprague-Dawley rats. The neurobehavioral score, cognitive function [as determined by the Morris water maze (MWM) test], neuronal number, and the Bax/Bcl-2 ratio was evaluated at 24 h after reperfusion in the presence or absence of CCPA (a selective A1 receptor agonist), DPCPX (a selective A1 receptor antagonist) into left lateral ventricle, or A1 short interfering RNA into the hippocampus area. The expression of the A1 receptor in the hippocampus was also investigated. The result showed that EA pretreatment upregulated the neuronal expression of the A1 receptor in the rat hippocampus at 90 min. And EA pretreatment reversed cognitive impairment, improved neurological outcome, and inhibited apoptosis at 24 h after reperfusion. Pretreatment with CCPA could imitate the beneficial effects of EA pretreatment. But the EA pretreatment effects were abolished by DPCPX. Furthermore, A1 receptor protein was reduced by A1 short interfering RNA which attenuated EA pretreatment-induced cognitive impairment.

Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

2020 ◽  
Author(s):  
Amteshwar Singh Jaggi
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Vascular Dementia ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Cerebral Ischemic ◽  
The Brain

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

Syringin protects against cerebral ischemia/reperfusion injury via inhibiting neuroinflammation and TLR4 signaling

Perfusion ◽  
2021 ◽  
pp. 026765912110070
Author(s):  
Yan Liu ◽  
Xuyao Zhu ◽  
Xiuxia Tong ◽  
Ziqiang Tan
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Learning And Memory ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Damage ◽  
Memory Ability ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Introduction: Cerebral ischemia/reperfusion injury (CI/R) is associated with high mortality and remains a large challenge in the clinic. Syringin is a bioactive compound with anti-inflammation, antioxidant, as well as neuroprotective effects. Nevertheless, whether syringin could protect against CI/R injury and its potential mechanism was still unclear. Methods: Rats were randomly divided into five groups: sham group, syringin group, CI/R group, CI/R + syringin group, and CI/R + syringin + LPS (TLR4 agonist) group. The CI/R injury rat model was established by the middle cerebral artery occlusion (MCAO). The learning and memory ability of rats was estimated by the Morris water maze test. Modified neurological severity score test (mNSS) and infarct volume were detected to assess the neuroprotective effect of syringin. ELISA and RT-qPCR were used to analyze the concentration of proinflammation cytokines and the expression of TLR4. Results: CI/R injury induced increased mNSS scores and decreased learning and memory ability of rats. Syringin could significantly protect against CI/R injury as it decreased the cerebral damage and improved the cognitive ability of CI/R rats. Moreover, syringin also reduced neuroinflammation of CI/R injury rats. Additionally, TLR4 was significantly upregulated in CI/R injury rats, which was suppressed by syringin. The activation of TLR4 reversed the neuroprotective effect of syringin in CI/R rats. Conclusion: Syringin decreased the inflammation reaction and cerebral damage in CI/R injury rats. The neuroprotective effect of syringin may be correlated with the inhibition of TLR4.

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