Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic–reperfusion associated cognitive dysfunction in aged mice

Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

doi:10.1016/j.pbb.2015.01.015

Cited by 10 publications

(13 citation statements)

References 46 publications

(64 reference statements)

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“…This impairment of cognition induced by repeated high sustained +Gz exposure is supposedly similar to the damage of ischemia-reperfusion owing to the fact that the brain may produce ischemia under +Gz condition. Ischemia-reperfusion causes reactive oxygen species overproduction and cholinergic system dysfunction [ 28 – 30 ]. Cholinergic signaling pathway is involved in central cognitive processes such as learning and memory [ 31 – 33 ]; cholinergic deficit is a major neuropathological feature that is associated with memory loss and closely correlated with the severity of cognitive dysfunction in AD [ 34 ] and poststroke cognitive impairments [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure

Chen

Zhao

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Repeated high sustained positive Gz (+Gz) exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb) has been reported to have neuroprotective effects and cognition-enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM) was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) but reduce the production of malondialdehyde (MDA). Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system.

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Section: Discussionmentioning

confidence: 99%

Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure

Chen

Zhao

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…Searches retrieved 138 PubMed records and 522 records from Medline, PsycINFO® and Embase. Of these, seven were review articles [ 6 – 12 ], 19 articles presented results from animal studies exploring mechanisms [ 13 – 31 ], and there were five human studies of which one was an autopsy study [ 32 ], two human cerebrospinal fluid (CSF) studies [ 33 , 34 ], one small RCT [ 35 ], and one in vivo human cell study [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

“…The methodology of the 19 animal studies varied widely in the selection of animals and drugs used, length of treatment times, and outcomes. Animal models ranged from mouse models using wild-type mice [ 13 , 23 ], aged Swiss mice [ 31 ], wild-type mice treated with icv amyloid beta 25–35 to be used as an AD mouse model [ 27 ], and transgenic (Tg) AD mice alone [ 17 , 19 , 21 , 29 , 30 ], to rat models such as Wistar [ 18 , 20 ], Sprague-Dawley [ 16 , 22 ], or spontaneously hypertensive rats (SHR) [ 14 , 15 , 24 , 26 , 28 ]. Regarding AHM used, 17 of the 19 studies used CCB, ACE-I, or ARB alone or in combination.…”

Section: Resultsmentioning

confidence: 99%

“…The renin inhibitor aliskiren was used in one study [ 13 ]. CCBs used included azelnidipine [ 24 ], isradipine [ 20 , 30 ], lercanidipine [ 14 ], nicardipine [ 14 , 16 , 19 , 20 , 30 ], nifedipine [ 30 ], nimodipine [ 16 , 20 , 22 , 30 ], and a nonselective CCB flunarizine [ 31 ]. Other antihypertensives included BBs such as carvedilol and propranolol [ 19 ], diuretics such as amiloride and furosemide [ 19 ], and hydralazine [ 14 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…Cognitive measures included water maze [ 15 , 16 , 19 – 21 , 25 , 26 , 31 ], Y maze [ 13 , 18 ], object recognition [ 21 , 27 ], passive avoidance [ 18 ], open field [ 15 , 22 ], and spontaneous alternation [ 27 ] tests. Locomotor function was assessed in five studies [ 22 , 24 , 26 , 27 , 31 ]. Numerous studies used serum, cerebrospinal fluid, or histopathological measures of amyloid beta and/or tau levels as their outcome [ 17 , 19 , 21 , 23 , 25 , 29 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

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Relationship Between Antihypertensive Medications and Cognitive Impairment: Part II. Review of Physiology and Animal Studies

et al. 2016

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Purpose of ReviewThere is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHM) and dementia risk are less clear. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews provide comprehensive review. Our extensive review includes 24 mechanistic animal and human studies published over the last 5 years assessing relationship between AHM and cognitive function.Recent FindingsAll classes of AHM showed similar result patterns in animal studies. The mechanism by which AHM exert their effect was extensively studied by evaluating well-established pathways of AD disease process, including amyloid beta (Aβ), vascular, oxidative stress and inflammation pathways, but only few studies evaluated the blood pressure lowering effect on the AD disease process.SummaryMethodological limitations of the studies prevent comprehensive conclusions prior to further work evaluating AHM in animals and larger human observational studies, and selecting those with promising results for future RCTs.

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Suppression of TLR4/NF-κB Signaling Pathway Improves Cerebral Ischemia–Reperfusion Injury in Rats

et al. 2017

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The present study aimed to investigate the effects of the toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-ҡB) signaling pathway in cerebral ischemia-reperfusion injury. A total of 125 male Sprague Dawley (SD) rats were selected for this study. Fifty SD rats were randomly divided into the control, sham injury, 0.5 h perfusion, 2 h perfusion, and 6 h perfusion groups to establish the model of ischemia-reperfusion. The rat brain injury model was established using the other 75 male SD rats, and different model groups with different treatments were established (15 rats per group): model control group (injected with 10 μL of saline solution), model + TAK-242 group (injected with resatorvid), model + PDTC group (injected with pyrrolidine dithiocarbamate), model + LPS group (injected with lipopolysaccharide), and sham injury group (incision to the neck skin and injected with 10 μL of saline solution for normal rats). These five groups were further assigned into three subgroups: day 3 group, day 7 group, and day 21 group. To determine how the TLR4/NF-қB signal pathway affects cerebral ischemia-reperfusion injuries, various methods including the Morris water maze, triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and western blotting were employed in this study. No neurological deficit was observed in rats from the model control and sham injury groups. A slight neurological deficit was found in the 0.5 h reperfusion group, while in the 2 and 6 h perfusion groups, neurological dysfunction was evident. Compared to the sham injury group, the model control group displayed a longer escape latency (EL) and increased cerebral infarction volume and pathological changes with enhanced expression of TLR4 and NF-κB (all P < 0.05). The inhibition of the TLR4/NF-κB signal pathway shortened rat EL and diminished cerebral infarction volume, and the pathological changes became less evident (all P < 0.05), while the activation of the TLR4/NF-κB signal pathway elongated rat EL, enlarged infarction volume, and increased cerebral pathological change (all P < 0.05). Pearson correlation analysis demonstrated that TLR4/NF-κB expression is correlated with the extent of rat brain damage. Cerebral ischemia-reperfusion injury in rats can be alleviated via the inhibition of the TLR4/NF-κB signaling pathway.

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Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic–reperfusion associated cognitive dysfunction in aged mice

Cited by 10 publications

References 46 publications

Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure

Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure

Relationship Between Antihypertensive Medications and Cognitive Impairment: Part II. Review of Physiology and Animal Studies

Suppression of TLR4/NF-κB Signaling Pathway Improves Cerebral Ischemia–Reperfusion Injury in Rats

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