Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils

Min, Dongyu; Mao, Xiao‐Yuan; Wu, Kun-Can; Cao, Yonggang; Guo, Feng; Zhu, Shu; Xie, Ni; Wang, Lei; Chen, Tianbao; Shaw, Chris; Cai, Jiyang

doi:10.1016/j.neulet.2011.12.064

Cited by 49 publications

(32 citation statements)

References 32 publications

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“…Furthermore, the expression level was higher in the 14 days than the three days group, which indicated that rolipram had the ability to enhance the level of p-CREB. The results showed that rolipram administration for a longer period of time induced enhanced protection in the ischemic rats, which was consistent with previous results found in studies using donepezil (28) and resveratrol (29). These previous studies showed that increasing the level of p-CREB could not only ameliorate focal ischemia-induced neuronal death but also the level of the downstream protein B-cell lymphoma 2 (Bcl-2) in the ischemic cortex of rats with tMCAO.…”

Section: Discussionsupporting

confidence: 91%

“…As described above, the level of p-CREB in the hippocampus increases following hypoxic-ischemic injury; therefore, increasing p-CREB levels may a potential strategy for the treatment of cerebral ischemia. To date, the role of p-CREB in ischemic injury following experimental tMCAO has been explored in diverse pharmacological interventions (28,29). In the present study, rolipram treatment lasting for three, seven and 14 days was utilized.…”

Section: Discussionmentioning

confidence: 99%

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Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

Cao

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated-(p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

Cao

et al. 2015

Experimental and Therapeutic Medicine

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“…In the present study, donepezil resulted in the absence of dark neurons with corkscrew dendrites in the cerebral cortex of AlCl 3 -treated rats. Other researchers have reported a neuroprotective action for donepezil in transient global cerebral ischemia, with the drug inhibiting delayed neuronal death in the hippocampal CA1 region (Min et al 2012). Donepezil also attenuated neuronal death (preserved neurons in the CA1 region of the hippocampus) following mild traumatic brain injury in rats.…”

Section: Discussionmentioning

confidence: 90%

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

et al. 2014

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Alzheimer's disease is the leading cause of dementia in the elderly. Depression is a common psychiatric disorder affecting individuals across life span and often arises in the context of pre-dementia, dementia, and Alzheimer's disease. The present study aimed to investigate the effects of the antidepressant drugs clomipramine (14.2 and 56.9 μmol/kg), fluoxetine (14.5 and 57.8 μmol/kg), and sertraline (14.6 and 58.4 μmol/kg) compared with acetylcholinesterase inhibitor donepezil (12 μmol/kg) on oxidative stress, memory impairment, and depressant-like behavior in a model of Alzheimer's disease induced by prolonged intraperitoneal administration of aluminum chloride (AlCl 3 ) (10 mg/kg/day for 60 days) in rats. Results indicated that the latency to find the hidden platform in Morris water maze (MWM) test increased by 100 %, while the immobility duration in forced swimming test (FST) increased by 51 % in AlCl 3 -treated rats. The administration of AlCl 3 resulted in increased brain malondialdehyde (MDA) by 58.6 % and nitric oxide (nitrite) concentrations by 71.7 %, while reduced glutathione (GSH) decreased by 35.6 % compared with the vehicle-treated group. Catalase and paraoxonase 1 (PON1) activities in the brain decreased by 41.8 and 18.3 %, respectively. Serum acetylcholinesterase (AChE) increased by 47.8 % and brain butyrylcholinesterase (BuChE) decreased by 23.1 % after AlCl 3 treatment. In AlCl 3 -treated rats, memory performance in the MWM test improved following donepezil and the highest dose of clomipramine, fluoxetine, and sertraline. The immobility duration in the FST was decreased by sertraline. Significant decrease in brain MDA occurred after treatment with clomipramine, fluoxetine, and a lower dose of sertraline. Reduced glutathione level increased by donepezil, clomipramine, and 57.8 μmol/kg fluoxetine. The level of nitric oxide decreased by donepezil (42.6 %), clomipramine (45.0 and 62.9 %), fluoxetine (21.9 and 40.9 %), and 14.6 μmol/kg sertraline (28.7 %). Catalase activity was restored by donepezil, fluoxetine, and sertraline and markedly increased by 56.9 μmol/kg clomipramine. Paraoxonase 1 activity was increased by 14.2 μmol/kg clomipramine. BuChE activity was unaltered, but AChE activity was decreased by donepezil, clomipramine, and fluoxetine compared with the AlCl 3 control group. AlCl 3 resulted in neurodegeneration (gliosis), extensive dark neurons with corkscrew dendrites, and degeneration of some Purkinje cell. Following donepezil treatment, no dark neurons were observed, while increased granular cell layer was observed after the administration of a high dose of clomipramine, fluoxetine, or sertraline. The results suggested that in rats treated with AlCl 3 , (i) donepezil, sertraline, clomipramine, and fluoxetine improve memory performance; (ii) sertraline was particularly effective in improving depressive-like behavior in this model and might be of value in the treatment of depressive symptoms associated with Alzheimer's disease; (iii) donepezil, clomipramine, and fluoxetine alleviated oxi...

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“…This is known as ''selective vulnerability'' in the brain induced by lethal transient ischemic insult [24]. Mongolian gerbils that have been used as an excellent animal to study mechanisms of selective neuronal death following transient global cerebral ischemia [25,26], because about 90 % of the gerbils lack the communicating vessels between the carotid and vertebral circulations [27,28]. We found a significant loss of pyramidal neurons in stratum pyramidale of the ischemic CA1 region in the ischemia-groups 5 days after ischemia-reperfusion using NeuN immunohistochemistry and F-J B histofluorescence staining.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia

et al. 2015

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Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia could reduce neuronal damage/death following a subsequent lethal transient cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2 and tumor necrosis factor (TNF)-α as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between animals with lethal ischemia and ones with IPC followed by lethal ischemia. In the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however, IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions of all cytokines were significantly decreased in the SP after lethal ischemia and hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4 and IL-13) in the stratum pyramidale of the CA1 region following no lethal ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC were continuously maintained is the SP of the CA1 region after lethal ischemia. However, pro-inflammatory cytokines (IL-2 and TNF-α) in the SP of the CA1 region were similar those in the sham-operated animals with IPC, and the IL-4 and IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion, this study shows that anti-inflammatory cytokines significantly increased and longer maintained by IPC and this might be closely associated with neuroprotection after lethal transient cerebral ischemia.

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Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils

Cited by 49 publications

References 32 publications

Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia

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