Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway

Srivastava, Niraj Kumar; Mukherjee, Somnath; Sharma, Rajkumar; Das, Jharana; Sharma, Rachna; Kumar, Vikas; Sinha, Neeraj; Sharma, Deepak

doi:10.1007/s11033-019-04626-9

Cited by 17 publications

(11 citation statements)

References 51 publications

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“…Then, the activation of repair mechanism would promote the liver to synthesize a large amount of TGs and phospholipids which are transported from the liver to brain via the blood through the blood−brain barrier. 42 Thus, the detected elevation of phospholipids PCs, lysoPC, PEs could be associated with the activation of self-repair mechanism. Also, earlier studies have reported that brain PC biosynthesis and phospholipase C activity were significantly increased after TBI.…”

Section: ■ Results and Discussionmentioning

confidence: 96%

“…The elevation of PCs, lysoPC, lysoPS, PEs, and DGs could be explained by the reported “self-repair” mechanisms in lesion area at chronic phase of TBI activated by neuroinflammation. It was reported that trauma causes three temporally overlapping responses in the brain: primary injuries, secondary injuries, and “self-repair” mechanisms. ,, Brain injury triggers inflammatory cascades and oxidative stress during secondary injury, and repair mechanism will be activated by the triggered oxidative-stress and inflammatory process. Then, the activation of repair mechanism would promote the liver to synthesize a large amount of TGs and phospholipids which are transported from the liver to brain via the blood through the blood–brain barrier .…”

Section: Resultsmentioning

confidence: 99%

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Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase

et al. 2021

ACS Chem. Neurosci.

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Traumatic brain injury (TBI) is a complex disease process that may contribute to temporary or permanent disability. Tracking spatial changes of lipids and metabolites in the brain helps unveil the underlying mechanisms of the disease procession and therapeutic response. Here, the liquid microjunction surface sampling technique was used for mass spectrometry imaging of both lipids and metabolites in rat models of controlled cortical impact with and without XueFu ZhuYu decoction treatment, and the work was focused on the diffuse changes outside the injured area at chronic phase (14 days after injury). Quantitative information was provided for phosphotidylcholines and cerebrosides by adding internal standards in the sampling solvent. With principal component analysis for the imaging data, the midbrain was found to be the region with the largest diffuse changes following TBI outside the injured area. In detail, several phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids, and diacylglycerols were found to be significantly up-regulated particularly in midbrain and thalamus after TBI and XFZY treatment. It is associated with the reported "self-repair" mechanisms at the chronic phase of TBI activated by neuroinflammation. Several glycosphingolipids were found to be increased in most of brain regions after TBI, which was inferred to be associated with neuroinflammation and oxidative stress triggered by TBI. Moreover, different classes of small matabolites were significantly changed after TBI, including fatty acids, amino acids, and purines. All these compounds were involved in 10 metabolic pathway networks, and 6 target proteins of XFZY were found related to the impacted pathways. These results shed light on the molecular mechanisms of TBI pathologic processes and therapeutic response.

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Section: ■ Results and Discussionmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase

et al. 2021

ACS Chem. Neurosci.

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“…Therefore, lipid peroxidation is the main form of neuronal oxidative damage. Indeed, lipid peroxidation is thought to be involved in the pathogenesis of PTE (Srivastava et al, 2019). Ferroptosis is a lipid peroxidation-dependent new form of oxidative cell death (Dixon et al, 2012; Mao et al, 2018), and can be inhibited by iron chelators and lipid peroxidation inhibitors (e.g., Fer-1 and Lipo-1).…”

Section: Discussionmentioning

confidence: 99%

Baicalein Exerts Neuroprotective Effects in FeCl3-Induced Posttraumatic Epileptic Seizures via Suppressing Ferroptosis

Jia

et al. 2019

Front. Pharmacol.

119

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Posttraumatic epilepsy (PTE) is a prevalent type of acquired epilepsy secondary to traumatic brain injury, and is characterized by repeated seizures. Traditional antiepileptic drugs have minimal response in preventing posttraumatic epileptic seizures. It is essential for the development of new therapeutic strategy. Our previous work disclosed a potent neuroprotective role of baicalein, a flavonoid extracted from Scutellaria baicalensis Georgi, against inherited epilepsy in rats. Whether baicalein has protective potential in posttraumatic epileptic seizures and the possible molecular mechanism remain elusive. Additionally, the brain is vulnerable to lipid peroxidation-induced damage due to high consumption of oxygen and abundant polyunsaturated fatty acids in neuronal membranes. Our present investigation aimed to elucidate whether baicalein exerts neuroprotective effects on posttraumatic epileptic seizures by inhibiting ferroptosis, a newly discovered lipid peroxidation-dependent cell death modality. We found that baicalein significantly reduced seizure score, number of seizures, and average seizure duration in an iron chloride (FeCl 3 )-induced PTE mouse model. The neuroprotective effect of baicalein was also validated in a ferric ammonium citrate (FAC)-induced HT22 hippocampal neuron damage model. Moreover, in vitro , baicalein could remarkably decrease ferroptotic indices (lipid reactive oxygen species, 4-hydroxynonenal, and prostaglandin endoperoxide synthase 2) and inhibit the expression of 12/15-lipoxygenase (12/15-LOX) in an iron-induced HT22 cell damage model. These findings were also validated in a mouse PTE model. It was concluded that baicalein exerted neuroprotective effects against posttraumatic epileptic seizures via suppressing ferroptosis and 12/15-LOX was likely to be involved in baicalein’s neuroprotection.

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“…It was recently shown that levels of phospholipids and cholesterol in the brain tissue of rats with post traumatic epilepsy were altered [36]. Acharya et al showed that picrotoxin-induced convulsions in rats led to alterations in lipid levels in the brain tissue along with structural changes in the microsomal membranes [37].…”

Section: Discussionmentioning

confidence: 99%

Ketogenic Diet: Impact on Cellular Lipids in Hippocampal Murine Neurons

2020

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Background: The mechanism of action of the ketogenic diet (KD), an effective treatment for pharmacotherapy refractory epilepsy, is not fully elucidated. The present study examined the effects of two metabolites accumulating under KD—beta-hydroxybutyrate (ßHB) and decanoic acid (C10) in hippocampal murine (HT22) neurons. Methods: A mouse HT22 hippocampal neuronal cell line was used in the present study. Cellular lipids were analyzed in cell cultures incubated with high (standard) versus low glucose supplemented with ßHB or C10. Cellular cholesterol was analyzed using HPLC, while phospholipids and sphingomyelin (SM) were analyzed using HPTLC. Results: HT22 cells showed higher cholesterol, but lower SM levels in the low glucose group without supplements as compared to the high glucose groups. While cellular cholesterol was reduced in both ßHB- and C10-incubated cells, phospholipids were significantly higher in C10-incubated neurons. Ratios of individual phospholipids to cholesterol were significantly higher in ßHB- and C10-incubated neurons as compared to controls. Conclusion: Changes in the ratios of individual phospholipids to cholesterol in HT22 neurons suggest a possible alteration in the composition of the plasma membrane and organelle membranes, which may provide insight into the working mechanism of KD metabolites ßHB and C10.

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Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway

Cited by 17 publications

References 51 publications

Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase

Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase

Baicalein Exerts Neuroprotective Effects in FeCl3-Induced Posttraumatic Epileptic Seizures via Suppressing Ferroptosis

Ketogenic Diet: Impact on Cellular Lipids in Hippocampal Murine Neurons

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