Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus

Martínez-Moreno, M.; Batlle, Montserrat; Ortega, Francisco J.; Gimeno-Bayón, Javier; Andrade, Carmen; Mahy, Nicole; Rodrı́guez, Manuel J.

doi:10.1016/j.neuroscience.2016.07.032

Cited by 6 publications

(2 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculated that this might be related to the inhibition of NeuN decrease or the promotion of neurogenesis by nicorandil. Martínez-Moreno et al have shown that KATP opener, Diazoxide, could protect neurons by being anti-inflammatory, and it may promote neurogenesis by reducing the synthesis of inflammatory compounds [43]. Further research on the role of nicorandil in ischemic stroke needs to be explored.…”

Section: Plos Onementioning

confidence: 99%

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke

Zhao

Yang

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

With population growth and aging, more and more patients with cerebral infarction have varying degrees of disability. ATP-sensitive potassium (KATP) channels regulate many cellular functions by coupling metabolic status with cell membrane electrical activity. Nicorandil (N-(2-hydroxyethyl)-nicotinamide nitrate) is the first KATP channel opener approved for clinical use. It has been reported that it might exert protective effects on the cerebral infarction by increasing cerebral blood flow and reducing inflammation. However, only a few studies explored its role in synaptogenesis. We made the rat model of middle cerebral artery occlusion (MCAO). Nicorandil was administered to rats via oral administration immediately after the surgery at a dose of 7.5 mg/kg and then daily for the next days. Infarct volume, cerebral edema, neurological deficits, cognitive impairment, and the level of Synaptophysin (SYP)、Growth associated protein-43 (GAP43) and neuronal nuclear antigen (NeuN) levels were measured to evaluate the effect of nicorandil. Our data showed that nicorandil treatment could decrease brain damage, improve learning and memory, and increase SYP、GAP43 and NeuN level. Taken together, we propose that nicorandil, as an opener of the KATP channel, provides a neuroprotective role in MCAO by promoting synaptic connections.

show abstract

Section: Plos Onementioning

confidence: 99%

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke

Zhao

Yang

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint (which this version posted May 8, 2024. ; https://doi.org/10.1101/2024.05.06.592741 doi: bioRxiv preprint long-term locomotion and coordination 3,10,11 , it worsens sensory function after SCI, likely by influencing glial cell activation 12 . Conversely, diazoxide, a specific KATP channel opener, mitigates damage-induced neurodegeneration and glial activation through KATP channel-mediated mitochondrial and cellular protection [13][14][15] . Therefore, an approach that can reduce PHN while preserving the beneficial effects of opening KATP channels may yield better outcomes for both motor and sensory function compared to glibenclamide or diazoxide used alone.…”

Section: Introductionmentioning

confidence: 99%

Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury

Xu,

Maskey,

et al. 2024

Preprint

View full text Add to dashboard Cite

Traumatic injury to the spinal cord (SCI) results in immediate necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progress hemorrhagic necrosis (PHN) and excessive excitation are the primary sources of neural injury triggered by various insults, causing neuronal cytotoxicity and the gradual enlargement of lesions. Recent approaches have involved blocking TRPM4, a contributor to PHN, using the sulfonylurea (SUR) subunits regulator glibenclamide. However, since SUR subunits are expressed in both neurons and glial cells in the spinal cord and sensory neurons, forming functional KATP channels, the use of glibenclamide can exacerbate the development of SCI-induced chronic pain. In this study, we explored a treatment strategy involving the administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals post-SCI. Our goal is to determine whether this approach significantly enhances both sensory and motor function. Contusive SCI was induced at spinal segment T10 in adult male and female rats. Immunostaining, electrophysiological recording in vitro, spectrophotometric assay, Western blot, and behavioral tests were performed to detect the outcomes. Results showed that the timed application of glibenclamide and diazoxide at various post-SCI time points significantly improved locomotor function and mitigated the development of SCI-induced chronic pain. These preclinical studies introduce a promising treatment strategy for addressing SCI-induced dysfunction.

show abstract

KATP Channel Expression and Genetic Polymorphisms Associated with Progression and Survival in Amyotrophic Lateral Sclerosis

et al. 2018

View full text Add to dashboard Cite

The ATP-sensitive potassium (K) channel directly regulates the microglia-mediated inflammatory response following CNS injury. To determine the putative role of the K channel in amyotrophic lateral sclerosis (ALS) pathology, we investigated whether ALS induces changes in K channel expression in the spinal cord and motor cortex. We also characterized new functional variants of human ABCC8, ABCC9, KCNJ8, and KCNJ11 genes encoding for the K channel and analyzed their association with ALS risk, rate of progression, and survival in a Spanish ALS cohort. The expression of ABCC8 and KCNJ8 genes was enhanced in the spinal cord of ALS samples, and KCNJ11 increased in motor cortex of ALS samples, as determined by real-time polymerase chain reaction. We then sequenced the exons and regulatory regions of K channel genes from a subset of 28 ALS patients and identified 50 new genetic variants. For the case-control association analysis, we genotyped five selected polymorphisms with predicted functional relevance in 185 Spanish ALS (134 spinal ALS and 51 bulbar ALS) patients and 493 controls. We found that bulbar ALS patients presenting the G/G genotype of the rs4148646 variant of ABCC8 and the T/T genotype of the rs5219 variant of KCNJ11 survived longer than other ALS patients presenting other genotypes. Also, the C/C genotype of the rs4148642 variant of ABCC8 and the T/C genotype of the rs148416760 variant of ABCC9 modified the progression rate in spinal ALS patients. Our results suggest that the K channel plays a role in the pathophysiological mechanisms of ALS.

show abstract

Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus

Cited by 6 publications

References 69 publications

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke

Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury

KATP Channel Expression and Genetic Polymorphisms Associated with Progression and Survival in Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About