Valproic Acid: A Potential Therapeutic for Spinal Cord Injury

Conghui, Zhou; Hu, Songfeng; Botchway, Benson O. A.; Zhang, Yong; Liu, Xuehong

doi:10.1007/s10571-020-00929-9

Cited by 4 publications

(4 citation statements)

References 89 publications

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“…We found some potential drugs by network analysis using the DHUB dataset, and the list was limited to launched drugs in the clinical field. Among the potential antagonists and agonists shown in Figure 8 , dextromethorphan [ 58 ], procaine [ 59 ], amiloride [ 60 ], dasatinib [ 61 ], dehydroepiandrosterone (DHEA) [ 62 ], (R)-(-)-apomorphine [ 63 ], D-serine [ 64 ], and valproic acid [ 65 , 66 ] have been extensively studied in clinical neuropharmacological studies aimed at modulation after neuronal damage. Dextromethorphan is mostly used as a cough suppressant and a drug for colds and coughs, but it has been reported to have neuroprotective effects against various disorders, including cerebral ischemia, epilepsy, and acute brain damage [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

“…Valproic acid (VPA) is an anticonvulsant drug and is also used for prophylaxis of migraine headache and treatment of manic episodes in patients with bipolar disorder [ 79 ]. VPA is a histone deacetylase inhibitor that affects the recovery of hyperacetylation and the reduction in the inflammatory response and has neuroprotective effects on histological and motor function recovery after SCI in animal models [ 65 , 66 ]. Nevertheless, clinical trials of VPA in SCI patients for the reduction of chronic pain in 1994 [ 80 ] and for functional recovery in 2019 [ 81 ] failed to reveal its efficacy in the clinical field.…”

Section: Discussionmentioning

confidence: 99%

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The Time Sequence of Gene Expression Changes after Spinal Cord Injury

Mun

Han

Hyun

2022

Cells

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Gene expression changes following spinal cord injury (SCI) are time-dependent, and an accurate understanding of these changes can be crucial in determining time-based treatment options in a clinical setting. We performed RNA sequencing of the contused spinal cord of rats at five different time points from the very acute to chronic stages (1 hour, 1 day, 1 week, 1 month, and 3 months) following SCI. We identified differentially expressed genes (DEGs) and Gene Ontology (GO) terms at each time point, and 14,257 genes were commonly expressed at all time points. The biological process of the inflammatory response was increased at 1 hour and 1 day, and the cellular component of the integral component of the synaptic membrane was increased at 1 day. DEGs associated with cell activation and the innate immune response were highly enriched at 1 week and 1 month, respectively. A total of 2841 DEGs were differentially expressed at any of the five time points, and 18 genes (17 upregulated and 1 downregulated) showed common expression differences at all time points. We found that interleukin signaling, neutrophil degranulation, eukaryotic translation, collagen degradation, LGI–ADAM interactions, GABA receptor, and L1CAM-ankyrin interactions were prominent after SCI depending on the time post injury. We also performed gene–drug network analysis and found several potential antagonists and agonists which can be used to treat SCI. We expect to discover effective treatments in the clinical field through further studies revealing the efficacy and safety of potential drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Time Sequence of Gene Expression Changes after Spinal Cord Injury

Mun

Han

Hyun

2022

Cells

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“…Recent studies suggest that VPA may be useful for the treatment of a wide range of pathologies, such as bipolar disorder [51][52][53], migraines [54][55][56], disorders related to motor disturbances [57,58], and even in cancer treatment [59][60][61]. Among these novel and promising applications of VPA, stands out its possible use as an anxiolytic agent [23,[62][63][64], due to the above mentioned agonistic action on the GABAergic system, similar to the mechanisms of action of benzodiazepines [21,24,64,65].…”

Section: Plos Onementioning

confidence: 99%

Unconditioned and conditioned anxiolytic effects of Sodium Valproate on flavor neophobia and fear conditioning

et al. 2023

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In three experiments with rats, we analyzed the potential anxiolytic effects of sodium valproate, an anticonvulsant drug that has shown additional pharmacodynamic effects in animal models, including anxiolytic action. Since previous results have revealed that injecting valproate before allowing animals to consume a novel flavor solution resulted in an attenuation of neophobia, we predicted a similar effect when the novel flavor is presented on a drug-free trial in the presence of a context previously associated with the drug. In line with this hypothesis, in our first experiment we observed a reduction in neophobia to a novel flavor for those animals tested in the presence of the context associated with Sodium Valproate. However, a control group that received the drug before being allowed access to the novel flavor showed a significant reduction in consumption. Experiment 2 revealed that the unconditioned effects of the drug include a deleterious effect on the animals’ locomotor activity that probably interferes with drinking behavior. Finally, in a third experiment, we directly tested the potential anxiolytic properties of sodium valproate by injecting the drug before implementing a fear conditioning procedure. These findings are explained in terms of the unconditioned anxiolytic action of the drug and the formation of an association between the context and the effects of the drug that evokes a conditioned response reminiscent of such anxiolytic effect.

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“… 1 , 2 The pathophysiological mechanisms of SCI include primary injury, which is the irreversibly mechanical injury, and secondary injuries caused by many factors, such as neuroinflammation, 3 , 4 neuronal loss, 5 , 6 and oxidative stress injury. 7 In the pathology of SCI, primary mechanical damage, an irreversible mechanical injury, rapidly leads to disruption of the blood‐spinal cord barrier 8 , 9 as well as neuronal loss. 5 , 6 Once impaired, neurons, which have a vital role in the central nervous system (CNS), are very difficult to regenerate.…”

Section: Introductionmentioning

confidence: 99%

Elamipretide reduces pyroptosis and improves functional recovery after spinal cord injury

Jiang

Ding

et al. 2023

CNS Neurosci Ther

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AimsElamipretide (EPT), a novel mitochondria‐targeted peptide, has been shown to be protective in a range of diseases. However, the effect of EPT in spinal cord injury (SCI) has yet to be elucidated. We aimed to investigate whether EPT would inhibit pyroptosis and protect against SCI.MethodsAfter establishing the SCI model, we determined the biochemical and morphological changes associated with pyroptosis, including neuronal cell death, proinflammatory cytokine expression, and signal pathway levels. Furthermore, mitochondrial function was assessed with flow cytometry, quantitative real‐time polymerase chain reaction, and western blot.ResultsHere, we demonstrate that EPT improved locomotor functional recovery following SCI as well as reduced neuronal loss. Moreover, EPT inhibited nucleotide‐binding oligomerization domain‐like receptor 3 (NLRP3) inflammasome activation and pyroptosis occurrence and decreased pro‐inflammatory cytokines levels following SCI. Furthermore, EPT alleviated mitochondrial dysfunction and reduced mitochondrial reactive oxygen species level.ConclusionEPT treatment may protect against SCI via inhibition of pyroptosis.

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Valproic Acid: A Potential Therapeutic for Spinal Cord Injury

Cited by 4 publications

References 89 publications

The Time Sequence of Gene Expression Changes after Spinal Cord Injury

The Time Sequence of Gene Expression Changes after Spinal Cord Injury

Unconditioned and conditioned anxiolytic effects of Sodium Valproate on flavor neophobia and fear conditioning

Elamipretide reduces pyroptosis and improves functional recovery after spinal cord injury

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