Neuroprotective Effects of Dilong on Cerebral Infarction in Rats

2020 ◽  
Vol 10 (4) ◽  
pp. 449-454
Author(s):  
Qijun Dai ◽  
Qin Xu ◽  
Pei Xu ◽  
Hongmei Yu ◽  
Yueqin Ding
Keyword(s):  
Cerebral Infarction ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neurological Impairment ◽  
Immunohistochemical Method ◽  
Tunel Staining ◽  
Antioxidant Enzyme Activities ◽  
Neuroprotective Effects ◽  
Stress Markers

Objective: The aim of the study was to investigate the effect of Dilong on cerebral infarction (CI) in a rat model. Methods: The neurological function of rats was evaluated with the mNSS. The expression of neurotrophic factors was determined using immunohistochemical method and western blotting. Hematoxylin-eosin (H&E) staining was arranged to observe the histopathologic changes. The infarct volume of brain in rats was arranged through TTC stain. Apoptosis was investigated by terminal dUTP nick end labeling (TUNEL) staining. The expressions of oxidative stress markers and pro-inflammatory cytokines were examined using ELISA assay. Results: Rats with CI manifested neurological impairment, elevated BDNF and NGF expression, augmented infarct area, enhanced neuronal apoptosis, increased antioxidant enzyme activities, decreased malondialdehyde (MDA) content in brain tissues, and accelerated production of inflammatory cytokines. With the treatment of Dilong, the neurological impairment, neuronal apoptosis, oxidative damage and inflammatory injury were all attenuated. Conclusion: Dilong could ameliorate CI in rats by anti-oxidant and antiinflammatory effects.

scholarly journals Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xiao Hu ◽  
Shirong Li ◽  
Desislava Met Doycheva ◽  
Lei Huang ◽  
Cameron Lenahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Neuronal Degeneration ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Artery Ligation ◽  
Neuroprotective Effects

Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.

scholarly journals Pharmacological activation of GPR55 improved cognitive impairment, neuroinflammation, oxidative stress and apoptosis induced by lipopolysaccharide in mice

2020 ◽  
Author(s):  
Xin Wang ◽  
Xiao Tong Xiang ◽  
Jie Hu ◽  
Yu Mei Wu ◽  
YueYue Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Sod Activity ◽  
Neuroprotective Effects ◽  
Impaired Performance ◽  
Pro Inflammatory Cytokines

Abstract BackgroundNeuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of Alzheimer’s disease (AD). The purpose of the present study was to investigate the neuroprotective effects and possible mechanism of G-protein coupled receptor 55 (GPR55) agonist, O-1602, on lipopolysaccharide (LPS)-induced cognitive deficits in mice. MethodsICR mice were treated with intracerebroventricular (i.c.v.) injection of LPS. Cognitive tests were performed, including the open field, Morris water maze, novel object recognition, and passive avoidance tests. The expression of GPR55, NF-κB p65, caspase-3, Bax and Bcl-2 were examined in the hippocampus by western blotting. Pro-inflammatory cytokines and microglia were detected by ELISA kit and immunohistochemical analyses, respectively. The malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were examined by assay kits. Furthermore, TUNEL-staining was used to detect neuronal apoptosis.ResultsI.c.v. injection of LPS exhibited impaired performance in the behavior tests, which were ameliorated by O-1602 treatment(2.0 or 4.0 μg/mouse, i.c.v.). Importantly, O-1602 reversed GPR55 down-regulation, decreased the expression of NF-κB p65, and suppressed the accumulation of pro-inflammatory cytokines and microglia activation, decreased malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity. In addition, O-1602 also significantly decreased Bax and increased Bcl-2 expression as well as decreased caspase-3 activity and TUNEL-positive cells, suppressed neuronal apoptosis in the hippocampus of LPS-treated mice.Conclusionswe conclude that O-1602 may ameliorate LPS-induced cognition deficits via inhibiting neuroinflammation, oxidative stress and apoptosis mediated by NF-κB signaling in mice.

scholarly journals Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sher-Wei Lim ◽  
Hui-Chen Su ◽  
Tee-Tau Eric Nyam ◽  
Chung-Ching Chio ◽  
Jinn-Rung Kuo ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Body Weight Loss ◽  
Motor Dysfunction ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Antibacterial Effects ◽  
Neuroprotective Effects ◽  
Tnf Α

Abstract Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

scholarly journals Electroacupuncture Ameliorates Cerebral I/R-Induced Inflammation through DOR-BDNF/TrkB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yue Geng ◽  
Yeting Chen ◽  
Wei Sun ◽  
Yingmin Gu ◽  
Yongjie Zhang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Cytokine Gene Expression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Mrna Levels ◽  
Anti Inflammatory

The beneficial effects of electroacupuncture (EA) at Shuigou (GV26) and Neiguan (PC6) on poststroke rehabilitation are critically related to the activation of the delta-opioid receptor (DOR). The underlying anti-inflammatory mechanisms in DOR activation and EA-mediated neuroprotection in cerebral ischemia/reperfusion (I/R) injury were investigated in the current study. Cell proliferation and apoptosis were detected by morphological changes, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release, and TUNEL staining. The mRNA levels were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR), and the protein expression was measured by western blot or enzyme-linked immunosorbent assay (ELISA) in vitro. Infarct volume was examined by cresyl violet (CV) staining, neurologic recovery was assessed by neurological deficit scores, and pro- and anti-inflammatory cytokines were determined by immunofluorescence in vivo. DOR activation greatly ameliorated morphological injury, reduced LDH leakage and apoptosis, and increased cell viability. It reversed the oxygen-glucose deprivation/reoxygenation- (OGD/R-) induced downregulation of DOR mRNA and protein, as well as BDNF protein. DOR activation also reduced proinflammatory cytokine gene expression, including TNF-α, IL-1β, and IL-6, and at the same time, increased anti-inflammatory cytokines IL-4 and IL-10 in OGD/R challenged PC12 cells. EA significantly reduced middle cerebral artery occlusion/reperfusion- (MCAO/R-) induced infarct volume and attenuated neurologic deficit scores. It markedly increased the expression of IL-10 and decreased IL-1β, while sham EA did not have any protective effect in MCAO/R-injured rats. DOR activation plays an important role in neuroprotection against OGD/R injury by inhibiting inflammation via the brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) pathway. The neuroprotective efficacy of EA at Shuigou (GV26) and Neiguan (PC6) on cerebral I/R injury may be also related to the inhibition of inflammatory response through the DOR-BDNF/TrkB pathway.

Abstract TP103: Activation of the Pi3k Pathway Plays Important Roles in Reduction of Cerebral Infarction by Cilnidipine

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Seong-Ho Koh ◽  
Jeong-Woo Son ◽  
Hojin Choi ◽  
Arum Yoo ◽  
Hyun-Hee Park ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Infarct Volume ◽  
Brain Mri ◽  
Pi3k Pathway ◽  
Control Group ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Western Blots ◽  
Neurobehavioral Function ◽  
Phosphorylated Akt

Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because hypertension is the main risk factor for cerebral infarction and most patients with hypertension take daily antihypertensive drugs, the neuroprotective effects and mechanisms of anti-hypertensive drugs need to be investigated. Cilnidipine, a long-acting, second-generation 1,4-dihydropyridine inhibitor of both L- and N-type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether cilnidipine has therapeutic effects in an animal model of cerebral infarction. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion (MCAO). Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2-hr occlusion. Western blots and immunohistochemistry were also performed after 24-hr occlusion. Initial infarct volume on DWI was not different between the cilnidipine group and the control group; however, FLAIR MRI at 24 hr showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of TUNEL-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated GSK-3β, and Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway.

Preventive and Therapeutic Effects of Ginsenoside Rb1 for Neural Injury During Cerebral Infarction in Rats

2013 ◽  
Vol 41 (02) ◽  
pp. 341-352 ◽  
Author(s):  
Zhou Jiang ◽  
Yuhui Wang ◽  
Xiaoyun Zhang ◽  
Tao Peng ◽  
Yun Lu ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Infarct Volume ◽  
Interleukin 1 ◽  
Protective Mechanism ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Ginsenoside Rb1 ◽  
Neural Injury ◽  
Neuroprotective Effects

To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction, we used a middle cerebral artery occlusion (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone as a control. Ginsenoside Rb1 was given to the rats by intragastric administration either before or after the MCAO surgery to study its preventive and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct volume than the positive control. Interleukin-1 (IL-1), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to determine brain damage and the recovery of nerves. These findings suggest that ginsenoside Rb1 has neuroprotective effects in rats, and the protection efficiency is higher than Edaravone. The protective mechanism is different from Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair ability in neuroprotection in vivo.

scholarly journals 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats

2020 ◽  
Vol 29 ◽  
pp. 096368972095022
Author(s):  
Liansheng Gao ◽  
Chun Wang ◽  
Bing Qin ◽  
Tao Li ◽  
Weilin Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Apoptosis ◽  
Neurological Impairment ◽  
White Matter Injury ◽  
Traumatic Spinal Cord Injury ◽  
Cyclin Dependent Kinase ◽  
Neuroprotective Effects ◽  
Cord Injury

Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprotective role of PFKFB3 in t-SCI. A compressive clip was introduced to establish the t-SCI model. Herein, we identified that PFKFB3 was extensively distributed in neurons, and PFKFB3 levels significantly increased and peaked 24 h after t-SCI. Additionally, knockdown of PFKFB3 inhibited glycolysis, accompanied by aggravated neuronal apoptosis and white matter injury, while pharmacological activation of PFKFB3 with meclizine significantly enhanced glycolysis, attenuated t-SCI-induced spinal cord injury, and alleviated neurological impairment. The PFKFB3 agonist, meclizine, activated cyclin-dependent kinase 1 (CDK1) and promoted the phosphorylation of p27, ultimately suppressing neuronal apoptosis. However, the neuroprotective effects of meclizine against t-SCI were abolished by the CDK1 antagonist, RO3306. In summary, our data demonstrated that PFKFB3 contributes robust neuroprotection against t-SCI by enhancing glycolysis and modulating CDK1-related antiapoptotic signals. Moreover, targeting PFKFB3 may be a novel and promising therapeutic strategy for t-SCI.

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chung-Che Lu ◽  
Tee-Tau Eric Nyam ◽  
Jinn-Rung Kuo ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glutamate Receptor ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Abstract Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

scholarly journals The Blood Component Iron Causes Neuronal Apoptosis Following Intracerebral Hemorrhage via the PERK Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Muyao Wu ◽  
Rong Gao ◽  
Baoqi Dang ◽  
Gang Chen
Keyword(s):  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Tunel Staining ◽  
Blood Component ◽  
Blood Components ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Protein Levels ◽  
Neurological Score

PERK signaling pathway plays an important role in neuronal apoptosis after Intracerebral hemorrhage (ICH). ICH can cause the release of blood components into the brain. However, which component in the blood plays a major role still unclear. This study was designed to investigate the activation of the PERK pathway in different blood components after ICH and explore which components have major relationships with neuronal apoptosis. Eighty-five Sprague–Dawley rats were used to establish an ICH model. Western blot (WB) and immunofluorescence (IF) were used to evaluate the expression of the PERK pathway. TUNEL staining, FJC staining and neurological score were used to evaluate neuronal apoptosis and necrosis after ICH. The results showed that protein levels of p-PERK and p-eIF2α were upregulated following ICH with the injection of Fe3+ and Fe2+ after 48 h. Then, deferoxamine (DFX) was used to study the roles of Fe3+ in ICH through the PERK signaling pathway. The results showed that injection of DFX reversed increasing protein levels and prevented neuronal apoptosis. Thus, iron plays an important role in ICH through the PERK signaling pathway. Furthermore, the reduction of iron demonstrates neuroprotective effects in ICH. This suggests that targeting intervention of the iron and PERK pathway could be an effective treatment strategy to improve ICH prognosis.

Protective role of protocatechuic acid in sevoflurane-induced neuron apoptosis, inflammation and oxidative stress in mice

2020 ◽  
Vol 38 (4) ◽  
pp. 323-331
Author(s):  
Yuhua Gao ◽  
Liping Ma ◽  
Tao Han ◽  
Meng Wang ◽  
Dongmei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Protocatechuic Acid ◽  
Protective Role ◽  
Continuous Treatment ◽  
Tunel Staining ◽  
Neuroprotective Effects ◽  
Tnf Α ◽  
Pre Treatment ◽  
And Oxidative Stress

Background: In neonatal mice, sevoflurane, inspired through the nasal cavity to act as anesthesia, triggers neuronal apoptosis, inflammation and oxidative injury that can hamper cognitive functions in the growth of the central nervous system in the later stages of life. Objective: Our study aimed to explore the potential neuroprotective effects of protocatechuic acid (PCA) to ameliorate neonatal sevoflurane-induced neurotoxicity. Methods: Male mice were pretreated with PCA (10 or 20 mg/kg) for half an hour before continuous treatment for 6 h with 3 % sevoflurane. TUNEL staining was performed to examine the apoptotic cells to record their count. ELISA was performed to evaluate the expressions of the proteins - IL-1β, IL-18 and TNF-α. Analysis of the Western blot and test of the Morris maze was determined and the results analyzed. Results: TUNEL findings assay showed a significant reduction with sevoflurane in neuronal apoptosis treated with PCA at 20 mg/kg. The expression of protein Caspase-3 showed significant changes in the group SEV + PCA (20 mg/kg). ELISA analysis showed that the levels of IL-18 and TNF-α were significantly reduced in the SEV + PCA (20 mg/kg) group as compared to SEV + PCA (10 mg/kg) group. MDA, ROS and SOD levels were noted to decrease significantly only in the SEV + PCA group (20 mg/kg) while IL-1β levels decreased in both SEV + PCA groups (10 or 20 mg/kg) respectively. Conclusions: Our findings imply that apoptosis, inflammation, and oxidative stress in the hippocampal region of neonatal mouse brain were significantly reduced by pre-treatment with PCA before sevoflurane exposure. Therefore, suggesting a role for PCA as a novel therapeutic agent in the treatment of sevoflurane anesthesia-induced neurobehavioral dysfunction.

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