Neuroprotective effect of ketamine against TNF‐α‐induced necroptosis in hippocampal neurons

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.

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The Effects of Propofol on Hypoxia- and TNF-α-Mediated Brain-Derived Neurotrophic Factor/Tyrosine Kinase Receptor B Pathway Dysregulation in Primary Rat Hippocampal Neurons and Astrocytes

10.21203/rs.3.rs-607889/v1 ◽

2021 ◽

Author(s):

Weiping Tao ◽

Xuesong Zhang ◽

Juan Ding ◽

Shijian Yu ◽

Peiqing Ge ◽

...

Keyword(s):

Tyrosine Kinase ◽

Neurotrophic Factor ◽

Neurological Disorders ◽

Hippocampal Neurons ◽

Inhibitory Effect ◽

Tyrosine Kinase Receptor ◽

Protective Properties ◽

Tnf Α ◽

Underlying Mechanisms ◽

Pathway Dysregulation

Abstract Background: BDNF/TrkB pathway dysregulation may be induced by hypoxia and inflammation, and play pivotal roles during the development of neurological disorders. Propofol is an anesthetic agent with neuro-protective properties. We aimed to verify whether propofol affected BDNF/TrkB pathway in neurons exposed to hypoxia or TNF-α.Methods: Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The production of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms such as ERK, CREB, p35 and Cdk5 were investigated.Results: In hippocampal neurons and astrocytes, hypoxia and TNF-α reduced the production of BDNF. Pretreatment of hippocampal neurons with 25μM propofol reversed the inhibitory effect of hypoxia or TNF-α on BDNF production. However, even 100μM propofol had no such effect in astrocytes. Further, we found that in hippocampal neurons hypoxia and TNF-α increased the phosphorylaion of ERK (p-ERK) and CREB at Ser142 (p-CREBSer142), while reduced the phosphorylation of CREB at Ser133 (p-CREBSer133), which were all reversed by 25μM propofol and 10μM ERK inhibitor. In addition, neither hypoxia nor TNF-α affected TrkB expression, truncation or phosphorylation in hippocampal neurons and astrocytes. However 50μM propofol induced TrkB phosphorylation without affecting its expression and truncation only in hippocampal neurons. Furthermore, we detected that in hippocampal neurons, 50μM propofol induced p35 expression and Cdk5 activation, and blockade of p35 or Cdk5 mitigated propofol-induced TrkB phosphorylation.Conclusions: Propofol, via ERK/CREB and p35/Cdk5, may modulate BDNF/TrkB pathway in hippocampal neurons that were exposed to hypoxia or TNF-α.

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Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy

Molecules ◽

10.3390/molecules25194359 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4359

Author(s):

Qi Zhang ◽

Jing Zhou ◽

Mi Shen ◽

Hui Xu ◽

Shu Yu ◽

...

Keyword(s):

Cell Viability ◽

Mitochondrial Dysfunction ◽

Neuroprotective Effect ◽

Pyrroloquinoline Quinone ◽

Transmission Electron ◽

Bv2 Cells ◽

Mitochondrial Functions ◽

Tnf Α ◽

Bv2 Microglia ◽

Factor Α

Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson’s disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

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Novel neuroprotective effect of cisternal and intra-cerebral magnesium sulfate solution infusion on delayed cerebral death in rat hippocampal neurons after transient global ischemia

Brain Research ◽

10.1016/j.brainres.2012.07.039 ◽

2012 ◽

Vol 1480 ◽

pp. 72-80 ◽

Cited By ~ 8

Author(s):

Kentaro Mori ◽

Takuji Yamamoto ◽

Yasuaki Nakao ◽

Masahiro Miyazaki ◽

Junko Iwata ◽

...

Keyword(s):

Magnesium Sulfate ◽

Hippocampal Neurons ◽

Neuroprotective Effect ◽

Sulfate Solution ◽

Global Ischemia ◽

Transient Global Ischemia ◽

Magnesium Sulfate Solution

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Enriched environment improves behavioral performance and attenuates inflammatory response induced by TNF-α in healthy adult mice

European Journal of Inflammation ◽

10.1177/1721727x17730471 ◽

2017 ◽

Vol 15 (3) ◽

pp. 200-209 ◽

Cited By ~ 2

Author(s):

Shehong Zhang ◽

Hongyu Xie ◽

Yuyang Wang ◽

Dake Li ◽

Liang Du ◽

...

Keyword(s):

Cognitive Performance ◽

Calcium Binding ◽

Healthy Adult ◽

Neuroprotective Effect ◽

Enriched Environment ◽

Immunomodulatory Effect ◽

Enzyme Linked Immunosorbent Assay ◽

Behavioral Performance ◽

Adult Mice ◽

Tnf Α

Several studies have demonstrated the neuroprotective effect of enriched environment (EE) and its positive effect on cognitive performance in pathological conditions, such as neurodegenerative diseases, epilepsy, and traumatic brain injury. However, the immunomodulatory effect of EE in normal rodents is not well characterized. To assess the immunomodulatory effect of EE, we randomly assigned normal mice to EE housing or standard environmental (SE) housing for 3 weeks. Behavioral alterations were evaluated by open field, fear conditioning, and Morris water maze tests. Immunohistochemical staining was performed to assess the expression of behavioral-related proteins, and enzyme-linked immunosorbent assay (ELISA) for brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was also performed. We also measured the levels of RIP1 and RIP3 proteins using western blotting. EE significantly improved the cognitive performance which was associated with the increased expressions of BDNF, ionized calcium-binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP); EE did not influence any morphological changes in the brain tissue in adult mice; however, increased resistance to inflammation induced by TNF-α was observed. These findings indicate that EE can positively influence cognitive and behavioral performance in healthy adult mice by exerting environ-immuno effect on neural function.

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Neuroprotective effect of Nrf2 activator dimethyl fumarate, on the hippocampal neurons in chemical kindling model in rat

Epilepsy Research ◽

10.1016/j.eplepsyres.2018.02.011 ◽

2018 ◽

Vol 143 ◽

pp. 98-104 ◽

Cited By ~ 7

Author(s):

Neha Singh ◽

Sheekha Vijayanti ◽

Lekha Saha ◽

Alka Bhatia ◽

Dibyajyoti Banerjee ◽

...

Keyword(s):

Hippocampal Neurons ◽

Neuroprotective Effect ◽

Dimethyl Fumarate ◽

Kindling Model ◽

Chemical Kindling ◽

Nrf2 Activator

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Telomerase increasing compound protects hippocampal neurons from amyloid beta toxicity by enhancing the expression of neurotrophins and plasticity related genes

Scientific Reports ◽

10.1038/s41598-019-54741-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Natalie Baruch-Eliyahu ◽

Vladislav Rud ◽

Alex Braiman ◽

Esther Priel

Keyword(s):

Oxidative Stress ◽

Amyloid Beta ◽

Neurotrophic Factors ◽

Hippocampal Neurons ◽

Neuroprotective Effect ◽

Adult Brain ◽

Beta Catenin ◽

Adult Mice ◽

Hippocampal Cell Culture ◽

Neuronal Degradation

AbstractThe telomerase reverse transcriptase protein, TERT, is expressed in the adult brain and its exogenic expression protects neurons from oxidative stress and from the cytotoxicity of amyloid beta (Aβ). We previously showed that telomerase increasing compounds (AGS) protected neurons from oxidative stress. Therefore, we suggest that increasing TERT by AGS may protect neurons from the Aβ-induced neurotoxicity by influencing genes and factors that participate in neuronal survival and plasticity. Here we used a primary hippocampal cell culture exposed to aggregated Aβ and hippocampi from adult mice. AGS treatment transiently increased TERT gene expression in hippocampal primary cell cultures in the presence or absence of Aβ and protected neurons from Aβ induced neuronal degradation. An increase in the expression of Growth associated protein 43 (GAP43), and Feminizing locus on X-3 genes (NeuN), in the presence or absence of Aβ, and Synaptophysin (SYP) in the presence of Aβ was observed. GAP43, NeuN, SYP, Neurotrophic factors (NGF, BDNF), beta-catenin and cyclin-D1 expression were increased in the hippocampus of AGS treated mice. This data suggests that increasing TERT by pharmaceutical compounds partially exerts its neuroprotective effect by enhancing the expression of neurotrophic factors and neuronal plasticity genes in a mechanism that involved Wnt/beta-catenin pathway.

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Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Journal of Endocrinology ◽

10.1677/joe-10-0040 ◽

2010 ◽

Vol 205 (3) ◽

pp. 263-270 ◽

Cited By ~ 69

Author(s):

Jiyeon Lee ◽

Eunjin Lim ◽

Yumi Kim ◽

Endan Li ◽

Seungjoon Park

Keyword(s):

Cell Death ◽

Kainic Acid ◽

Hippocampal Neurons ◽

Therapeutic Potential ◽

Excitatory Amino Acid ◽

Neuroprotective Effect ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Proinflammatory Mediators ◽

Hippocampal Neurodegeneration

Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid l-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor α, interleukin-1β, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

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Anticonvulsant and Neuroprotective Activities ofPhragmanthera austroarabicaExtract in Pentylenetetrazole-Kindled Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/5148219 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Hibah M. Aldawsari ◽

Basma G. Eid ◽

Thikrayat Neamatallah ◽

Sawsan A. Zaitone ◽

Jihan M. Badr

Keyword(s):

Plant Extract ◽

Hippocampal Neurons ◽

Seizure Activity ◽

Chemical Constituents ◽

Neuroprotective Effect ◽

Intraperitoneal Administration ◽

Neuroprotective Activity ◽

Total Phenolic ◽

Control Group ◽

Phenolic Contents

Anticonvulsant and neuroprotective activity ofPhragmanthera austroarabicaextract were tested in pentylenetetrazole-kindled mice. All the chemical constituents of the plant extract were identified. Additionally, the extract was standardized and proved to contain total phenolic contents equal to379.92±1.32 mg gallic acid equivalents/g dry plant extract. Induction of kindling was achieved by repeated intraperitoneal administration of pentylenetetrazole (35 mg/kg) twice weekly. Male albino mice were givenP.austroarabicaextract (200, 400, or 800 mg/kg). The two higher doses (400 or 800 mg/kg) of the extract significantly caused notable reduction in seizure activity and hippocampal malondialdehyde level compared to pentylenetetrazole control group. The highest dose enhanced cortical GSH level and showed intact DNA in the laddering assay. Upon studying the neuroprotective effect, mice treated with the higher dose of the extract demonstrated an improvement in the percent of surviving neurons in the cortex and hippocampus. We concluded thatP. austroarabicaextract ameliorated seizure activity and protected cortical and hippocampal neurons against pentylenetetrazole-induced kindling in mice.

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