scholarly journals Neuronal damage and memory deficits after seizures are reversed by ascorbic acid?

2010 ◽  
Vol 68 (4) ◽  
pp. 579-585 ◽  
Author(s):  
Adriana da Rocha Tomé ◽  
Chistiane Mendes Feitosa ◽  
Rivelilson Mendes de Freitas
Keyword(s):  
Ascorbic Acid ◽  
Cognitive Dysfunction ◽  
Neuronal Damage ◽  
Memory Task ◽  
Memory Deficits ◽  
Reference Memory ◽  
Control Group ◽  
Hippocampal Region ◽  
Neuroprotective Effects ◽  
Epileptic Patients

The objective of the present study was to evaluate the neuroprotective effects of ascorbic acid (AA) in rats, against the neuronal damage and memory deficit caused by seizures. Wistar rats were treated with 0.9% saline (i.p., control group), ascorbic acid (500 mg/kg, i.p., AA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of ascorbic acid (500 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of ascorbic acid (AA plus pilocarpine group). After the treatments all groups were observed for 24 h. Pilocarpine group presented seizures which progressed to status epilepticus in 75% of the animals. Pretreatment with AA led to a reduction of 50% of this rate. Results showed that pretreatment with AA did not alter reference memory when compared to a control group. In the working memory task, we observed a significant day's effect with important differences between control, pilocarpine and AA plus pilocarpine groups. Pilocarpine and AA plus pilocarpine groups had 81 and 16% of animals with brain injury, respectively. In the hippocampus of pilocarpine animals, it was detected an injury of 60%. As for the animals tested with AA plus pilocarpine, the hippocampal region of the group had a reduction of 43% in hippocampal lesion. Our findings suggest that seizures caused cognitive dysfunction and neuronal damage that might be related, at least in part, to the neurological problems presented by epileptic patients. AA can reverse cognitive dysfunction observed in rats with seizures as well as decrease neuronal injury in rat hippocampus.

scholarly journals Time-restricted feeding alters isoflurane-induced memory deficits

2020 ◽  
Vol 11 (1) ◽  
pp. 341-355
Author(s):  
Jia Song ◽  
Shuaishuai Chu ◽  
Xin Fang ◽  
Fangxia Xu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Cognitive Dysfunction ◽  
Food Access ◽  
Memory Deficits ◽  
Daily Rhythm ◽  
Control Group ◽  
Restricted Feeding ◽  
Isoflurane Anaesthesia ◽  
Feeding Group ◽  
Night Feeding

AbstractFood consumption during the rest phase promotes circadian desynchrony, which is corrected with harmful physiological and mental disorders. Previously, we found that circadian desynchrony was involved in isoflurane-induced cognitive impairment. Here, we scheduled food access to modulate daily rhythm to examine its impact on isoflurane-induced cognitive impairments. Mice were randomly transferred to restricted feeding (RF) time groups: Control group (Zeitgeber time (ZT) 0–ZT24, ad libitum feeding), Day-Feeding group (ZT0–ZT12, misaligned feeding), and Night-Feeding group (ZT12–ZT24, aligned feeding). Then, some of them were subjected to 5 h of 1.3% isoflurane anaesthesia from ZT14 to ZT19 and were divided into the Control + Anes group, the Day-Feeding + Anes group, and the Night-Feeding + Anes group. Mini-Mitter was used to monitor the daily rhythm. Fear conditioning system was conducted to assess cognition of mice. We observed that the Night-Feeding group adapted to RF gradually, whereas the Day-Feeding group exhibited a disturbed daily rhythm. The Night-Feeding + Anes group exhibited a partially enhanced daily rhythm, whereas the Day-Feeding + Anes group exhibited sustained phase advances and diurnality score increase 7 days after isoflurane anaesthesia. Notably, in tests of hippocampus-dependent contextual memory, the Night-Feeding + Anes group demonstrated decreased deficits; the Day-Feeding + Anes group showed prolonged post-anaesthetic deficits 14 days after isoflurane anaesthesia. However, amygdala-dependent cued-fear conditioning post-anaesthesia was not altered by the RF schedule. In conclusion, we demonstrated that misaligned feeding disturbed the daily rhythm and led to persistent post-anaesthetic cognitive dysfunction. Aligned feeding enhanced the daily rhythm partially and improved post-anaesthetic cognitive dysfunction.

scholarly journals Roscovitine, a CDK5 Inhibitor, Alleviates Sevoflurane-Induced Cognitive Dysfunction via Regulation Tau/GSK3β and ERK/PPARγ/CREB Signaling

2017 ◽  
Vol 44 (2) ◽  
pp. 423-435 ◽  
Author(s):  
Jianhui Liu ◽  
Junjun Yang ◽  
Yinhua Xu ◽  
Gang Guo ◽  
Li Cai ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Neuronal Damage ◽  
Immunohistochemical Analysis ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Background/Aims: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. Methods: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups. Six-day-old wild-type mice were exposed to sevoflurane and then treated with the CDK5 inhibitor roscovitine. The effects on cognitive function were evaluated with the Morris water maze and neuronal damage in the hippocampus was assessed by immunohistochemical analysis. Results: CDK5 activation increased neuronal damage by inducing Tau/glycogen synthase kinase (GSK) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/cyclic AMP response element-binding protein (CREB) signaling following exposure to sevoflurane. CDK5 inhibition by roscovitine administration alleviated sevoflurane-induced neuronal damage and cognitive impairment. Conclusions: Inhibiting CDK5 with roscovitine has neuroprotective effects against neuronal injury and cognitive dysfunction caused by sevoflurane anesthesia that are exerted via modulation of Tau/GSK3β and ERK/PPARγ/CREB signaling.

scholarly journals Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Somayeh Taymouri ◽  
Abbas Pardakhty ◽  
Majid Asadi-Shekaari ◽  
Abodolreza Babaee
Keyword(s):  
Ascorbic Acid ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Size Change ◽  
Neuroprotective Effects

The objective of the present study was to prepare a stableivinjectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluatedin vitro. Forin vivoevaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C.In vivostudies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

scholarly journals The effect of intraoperative dexmedetomidine on cognitive dysfunction after surgery: a updated meta-analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianli Li ◽  
Qifan Yin ◽  
Xuejiao Xun ◽  
Jinhua He ◽  
Dongdong Yu ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Mmse Score ◽  
Meta Analysis ◽  
Postoperative Cognitive Dysfunction ◽  
Cochrane Library ◽  
Control Group ◽  
General Anaesthetic ◽  
Neuroprotective Effects ◽  
Systematic Analysis ◽  
The Cochrane Library

Abstract Background Postoperative cognitive dysfunction (POCD) is one of the most common. Neuroprotective effects of dexmedetomidine (DEX) are reported in previous studies but evidence regarding the POCD is still unclear. In order to gain latest evidence, the present study analyzes the outcomes of randomized controlled trials (RCTs) which utilized DEX with general anaesthesia perioperatively. Method Four online databases (PubMed, Embase, the Cochrane Library, and CNKI) were used to find relevant RCTs to conduct systematic analysis. All studies comparing the incidence of POCD or MMSE score between the DEX group and the placebo or comparator group in patients undergoing general anaesthetic surgery were eligible for inclusion. Based on the inclusion and exclusion criteria, the studies were selected. This meta-analysis was performed using odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and standardized mean difference (SMD) and 95% CIs for continuous data as effective measures. Results In total of 21 studies were included in this meta-analysis. The results showed that the incidence of POCD in DEX group was significantly lower than the control group on the first (OR = 0.36, 95% CI 0.24–0.54),third (OR = 0.45,95% CI 0.33–0.61) and seventh (OR = 0.40,95% CI 0.26–0.60) postoperative days; the MMSE scores in DEX group were higher than the control group on the first (SMD = 1.24, 95% CI 1.08–1.41), third(SMD = 1.09, 95%CI 0.94–1.24) and seventh (SMD = 3.28, 95% CI 1.51–5.04) postoperative days. Conclusions Intraoperative DEX use can ameliorate the POCD of patients who received surgical operations under general anesthesia, and effectively reduce the incidence of POCD and improve MMSE score.

Neuroprotective Effects of Salidroside Against Beta-Amyloid-Induced Cognitive Impairment in Alzheimer’s Disease Mice Through the PKC/p38MAPK Pathway

2020 ◽  
Vol 10 (2) ◽  
pp. 212-217
Author(s):  
Wei Li ◽  
Sixia Yang ◽  
Zeping Xie ◽  
Hui Lu ◽  
Junjun Ling ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Protein Expression ◽  
Cognitive Dysfunction ◽  
Neuronal Damage ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Neural Apoptosis ◽  
P38mapk Pathway

Alzheimer’s disease (AD) is a common neurodegenerative disease as well as the main cause of dementia. A progressive cognitive decline with age is considered as the major manifestation of AD. Amyloid beta-peptide (Aβ) is one of the primary causes leading to cognitive dysfunction in AD. Recent studies have suggested that the activation of PKC/p38MAPK pathway is related to the neurotoxicity induced by β-amyloid. Salidroside is the major active component of Rhodiola crenu-lata, has been reported with widely neuroprotective effects. The protective effects of salidroside against β-amyloid induced neural apoptosis via the MAPKs pathway has been confirmed in the vitro study. The present study aimed to investigate the neuroprotective effects of salidroside through the PKC/p38MAPK pathway in β-amyloid induced AD mice. The results by Y maze showed that salidroside improved Aβ-induced cognitive impairment. Nissl staining results showed that salidroside affected neuronal damage in hippocampus and cerebral cortex of AD mice. Western blot results revealed that salidroside enhanced protein expression of p-PKC, whereas it suppressed protein expression of p-p38MAPK, Bax and cleaved caspase-3. Thus, the present results demonstrated that salidroside ameliorated cognitive dysfunction in Aβ25–35 induced AD mice. And the effects on protein expression of p-PKC and p-p38MAPK contributed to the neuroprotective effects of salidroside against neural apoptosis in AD mice.

scholarly journals Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

2021 ◽  
Vol 13 (3) ◽  
pp. 109-115
Author(s):  
Xiaohu Liang ◽  
Xiaoqun Luo ◽  
Danping Li ◽  
Lingqiong Kong
Keyword(s):  
Cognitive Dysfunction ◽  
Calcium Binding ◽  
Neuronal Damage ◽  
Postoperative Cognitive Dysfunction ◽  
Neuron Specific Enolase ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects ◽  
Necrosis Factor Alpha ◽  
Aged Mice ◽  
Pyrin Domain

Ruscogenin exerts an anti-inflammatory effect in the pathogenesis of various human diseases, including pulmonary hypertension, acute lung injury, acute pancreatitis and cerebral ischemia. Its role in isoflurane-induced rats with postoperative cognitive dysfunction (POCD) was investigated in this study. Aged rats were exposed to isoflurane for establishing a model of POCD, and administered with ruscogenin by gavage. Cognitive dysfunction was evaluated by the Morris water maze test. Hematoxylin and Eosin (H&E) staining was designed to assess neuronal damage. Markers of brain damage and neuroinflammation were detected by enzyme-linked-immunosorbent serologic assay. Isoflurane exposure caused impaired cognitive function by increasing escape latency, decreasing the time taken for crossing target and time in target quadrant. However, administration of ruscogenin reversed these cognitive dysfunctions. Abnormal morphological phenomena on neurons and enhanced levels of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) were identified in mice post-isoflurane exposure. Administration of ruscogenin ameliorated the neuronal morphological damages and reduced the levels of S-100β and NSE in the hippocampi of isoflurane-induced aged mice. Ruscogenin also attenuated isoflurane-induced enhancements in the levels of Interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha in the hippocampi of mice. Isoflurane-induced enhancements in the mRNA expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, IL-1β and IL-18 proteins were also restored by administration of ruscogenin. Ruscogenin exerted neuroprotective effects against isoflurane-induced cognitive dysfunction and neuroinflammation through blocking of NLRP3 pathway.

scholarly journals The Effect of Intraoperative Dexmedetomidine on Cognitive Dysfunction After Surgery: A Updated Meta-Analysis

2021 ◽  
Author(s):  
Qifan Yin ◽  
Jianli Li ◽  
Xuejiao Xun ◽  
Jinhua He ◽  
Dongdong Yu ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Mmse Score ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
General Anaesthetic ◽  
Neuroprotective Effects ◽  
Systematic Analysis ◽  
Dichotomous Data ◽  
The Cochrane Library

Abstract BackgroundPostoperative cognitive dysfunction (POCD) is one of the most common. Neuroprotective effects of dexmedetomidine(DEX) are reported in previous studies but evidence regarding the POCD is still unclear. In order to gain latest evidence, the present study analyzes the outcomes of randomized controlled trials(RCTs) which utilized DEX with general anaesthesia perioperatively.MethodFour online databases (PubMed, Embase, the Cochrane Library, and CNKI) were used to find relevant RCTs to conduct systematic analysis. All studies comparing the incidence of POCD or MMSE score between the DEX group and the placebo or comparator group in patients undergoing general anaesthetic surgery were eligible for inclusion. Based on the inclusion and exclusion criteria, the studies were selected. This meta-analysis was performed using odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and standardized mean difference (SMD) and 95% CIs for continuous data as effective measures.ResultsIn total of 21 studies were included in this meta-analysis. The results showed that the incidence of POCD in DEX group was significantly lower than the control group on the first (OR=0.36, 95% CI 0.24-0.54),third (OR=0.45,95% CI 0.33–0.61) and seventh (OR=0.40,95% CI 0.26–0.60) postoperative days; the MMSE scores in DEX group were higher than the control group on the first (SMD=1.24, 95% CI 1.08-1.41), third(SMD= 1.09, 95%CI 0.94-1.24) and seventh (SMD=3.28, 95% CI 1.51-5.04) postoperative days. ConclusionsIntraoperative DEX use can ameliorate the POCD of patients who received surgical operations under general anesthesia, and effectively reduce the incidence of POCD and improve MMSE score.

scholarly journals Perillaldehyde improves cognitive function in vivo and in vitro by inhibiting neuronal damage via blocking TRPM2/NMDAR pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yue Qiu ◽  
Xian-jun Xue ◽  
Geng Liu ◽  
Miao-miao Shen ◽  
Chun-yan Chao ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Western Blot ◽  
Cognitive Dysfunction ◽  
Neuronal Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Neuroprotective Effects ◽  
Mitochondrial Structure ◽  
L Value

Abstract Background Vascular cognitive dysfunction in patients with vascular dementia (VD) is a kind of severe cognitive dysfunction syndrome caused by cerebrovascular diseases. At present, effective drugs to improve the cognitive function of VD patients still need to be explored. Transient Receptor Potential Melastatin 2 (TRPM2) channel is a nonspecific cation channel that plays a key role in the toxic death of neurons. Perillaldehyde (PAE) has the protective effect of epilepsy and insomnia and other central nervous system diseases. The aim of this study is to explore whether PAE improves cognitive function in VD rats and to investigate the potential mechanisms in vivo and vitro. Methods VD rats were induced by bilateral common carotid arteries occlusion (2-vessel occlusion [2VO]) and treated with PAE for 4 weeks. The neuroprotective effects of PAE was subsequently assessed by the Morris water maze, hematoxylin–eosin (HE) staining, Golgi staining, electron microscopy, Neuron-specific nuclear protein (Neu N) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining. After primary hippocampal neurons were isolated, cell viability was detected by MTT assay and intracellular Ca2+ concentration was detected by calcium imaging assay. The content of Nitriteoxide (NO), Malondialdehyde (MDA) and Superoxide dismutase (SOD) activity in serum of rats were observed by Enzyme Linked Immunosorbent Assay (ELISA). Immunohistochemistry, Western blot, and Confocal laser scanning were used to detect the expression levels of N-methyl-d-asprtate receptor-2B (NR2B) and TRPM2. Results The results showed that PAE can improve the number and activity of neurons, increase the length and number of dendrites in hippocampus, decrease the Vv value and PE value of neuronal nucleus and mitochondrial structure significantly, increase the s value and L value in nucleus structure, decrease the s value and L value in mitochondrial structure, and improve the learning and memory ability of rats significantly. And PAE can strengthen the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA. The results of western blot, immunohistochemistry and immunofluorescence showed that PAE could reduce the level of TRPM2 and increase the expression of NR2B. Conclusions Taken together, our findings provide evidence that the neuroprotective effects of PAE in VD rats maybe through TRPM2 inhibition and subsequent activation of NMDAR signaling pathway.

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