Kainic Acid‐Induced Neurodegenerative Model: Potentials and Limitations

Zheng, Xiangyu; Zhang, Hong‐Liang; Luo, Qi; Zhu, Jian

doi:10.1155/2011/457079

Cited by 117 publications

(74 citation statements)

References 118 publications

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“…In addition to investigating the role that loss of EGFR has with traumatic brain injury we wanted to determine if EGFR ablated brains are susceptible to neurotoxicity‐induced neuronal death. One model routinely used to investigate such phenomenon is the triggering of seizures with Kainic acid (KA), a marine‐derived amino acid that has a very high activating potential of glutamate transporters 38, 39, 40, 41. Several molecules acting downstream of the EGFR have been implicated in mediating KA‐induced neurotoxicity 42, 43.…”

Section: Resultsmentioning

confidence: 99%

Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain

et al. 2018

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Mice lacking the epidermal growth factor receptor (EGFR) develop an early postnatal degeneration of the frontal cortex and olfactory bulbs and show increased cortical astrocyte apoptosis. The poor health and early lethality of EGFR−/− mice prevented the analysis of mechanisms responsible for the neurodegeneration and function of the EGFR in the adult brain. Here, we show that postnatal EGFR‐deficient neural stem cells are impaired in their self‐renewal potential and lack clonal expansion capacity in vitro. Mice lacking the EGFR in the brain (EGFRΔbrain) show low penetrance of cortical degeneration compared to EGFR−/− mice despite genetic recombination of the conditional allele. Adult EGFRΔ mice establish a proper blood–brain barrier and perform reactive astrogliosis in response to mechanical and infectious brain injury, but are more sensitive to Kainic acid‐induced epileptic seizures. EGFR‐deficient cortical astrocytes, but not midbrain astrocytes, have reduced expression of glutamate transporters Glt1 and Glast, and show reduced glutamate uptake in vitro, illustrating an excitotoxic mechanism to explain the hypersensitivity to Kainic acid and region‐specific neurodegeneration observed in EGFR‐deficient brains.

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Section: Resultsmentioning

confidence: 99%

Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain

et al. 2018

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“…Excitotoxicity is the pathological process where neurons are damaged or killed by overstimulation of glutamate receptors in the Central Nervous System (CNS) by excitatory amino acids and it is considered to be contributing factor in the pathogenesis of various neurodegenerative disorders in the CNS (Wang, et al, 2005;Zhu, 2011, Zheng, et al, 2011). It was earlier reported that stimulation of glutamate-KA receptors induces neuronal NO release, which in turn modulates glutamate transmission (Alabadi et al, 1999;Nakaki etal., 2000).…”

Section: Discussionmentioning

confidence: 99%

Propolis Ameliorates Tumor Nerosis Factor-α, Nitric Oxide levels, Caspase-3 and Nitric Oxide Synthase Activities in Kainic Acid Mediated Excitotoxicity in Rat Brain

Swamy¹,

Suhaili²,

Sirajudeen³

et al. 2014

Afr. J. Trad. Compl. Alt. Med.

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Background: Increased nitric oxide (NO), neuronal inflammation and apoptosis have been proposed to be involved in excitotoxicity plays a part in many neurodegenerative diseases. To understand the neuro-protective effects of propolis, activities of Nitric oxide synthase (NOS) and caspase-3 along with NO and tumor necrosis factor-α (TNF-α) levels were studied in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) in rats supplemented with propolis prior to excitotoxic injury with kainic acid (KA). Materials and methods: Male Sprague-Dawley rats were divided into four groups (n=6 rats per group) as Control, KA, Propolis and KA+Propolis. The control group and KA group have received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis +KA group were injected subcutaneously with kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs. CC, CB and BS were separated, homogenized and used for estimation of NOS, caspase-3, NO and TNF-α by commercial kits. Results were analyzed by one way ANOVA, reported as mean + SD (n=6 rats), and p<0.05 was considered statistically significant. Results: The concentration of NO, TNF-α, NOS and caspase-3 activity were increased significantly (p<0.001) in all the three brain regions tested in KA group compared to the control. Propolis supplementation significantly (p<0.001) prevented the increase in NOS, NO, TNF-α and caspase-3 due to KA. Conclusion:Results of this study clearly demonstrated that the propolis supplementation attenuated the NOS, caspase-3 activities, NO, and TNF-α concentration and in KA mediated excitotoxicity. Hence propolis can be a possible potential protective agent against excitotoxicity and neurodegenerative disorders.

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“…Kainic acid (KA), an agonist for the iGluR subtype which is known as a non-degradable analog of the excitotoxin, glutamate, offers a well-characterized model for the study of NDDs (Wang et al, 2005; Zhang et al, 2010; Zheng et al, 2010). DomA, a naturally occurring marine neurotoxin produced by members of the diatom genus, Pseudo-nitzschia , is a structural relative of KA (Lu et al, 2013).…”

Section: Glutamate Receptors As Potential Targets In Neurotoxic Agentmentioning

confidence: 99%

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Jakaria

Park

Haque

et al. 2018

Front. Mol. Neurosci.

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Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In in vivo and in vitro models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs. Moreover, therapeutic drugs might be discovered based on the studies employing these models. In NDD models, different neurotoxic agents, namely, kainic acid, domoic acid, glutamate, β-N-Methylamino-L-alanine, amyloid beta, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3-Nitropropionic acid and methamphetamine can potently impair both ionotropic and metabotropic glutamate receptors, leading to the progression of toxicity. Many other neurotoxic agents mainly affect the functions of ionotropic glutamate receptors. We discuss particular neurotoxic agents that can act upon glutamate receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent-induced disease characteristics with glutamate receptors would aid the discovery and development of therapeutic drugs for NDDs.

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Kainic Acid‐Induced Neurodegenerative Model: Potentials and Limitations

Cited by 117 publications

References 118 publications

Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain

Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain

Propolis Ameliorates Tumor Nerosis Factor-α, Nitric Oxide levels, Caspase-3 and Nitric Oxide Synthase Activities in Kainic Acid Mediated Excitotoxicity in Rat Brain

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

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