Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

Park, Hye-Seong; Lee, Bo Kyung; Park, Sok; Kim, Seung Up; Lee, Soo Hwan; Baik, Eun Joo; Lee, Jimin; Yi, Kyu Yang; Yoo, Sung Eun; Moon, Chang-Hyun; Jung, Yi‐Sook

doi:10.1016/j.brainres.2005.09.002

Cited by 28 publications

(24 citation statements)

References 23 publications

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“…Sabiporide has been reported to elicit cardioprotective effects in rat myocardial infarction model (Pisarenko et al, 2005) and rabbit heart failure model (Aker et al, 2004). In our previous study, we have demonstrated neuroprotective effects of sabiporide in cerebral ischemia model in vivo and in neuronal cell death model in vitro (Park et al, 2005). In addition, we also found that sabiporide elicited an ameliorating effect on brain edema in cerebral ischemia model.…”

Section: Introductionmentioning

confidence: 66%

“…Because exceptionally elevated levels of [Ca 2+ ] i during ischemia/ hypoxia can cause neuronal death and BBB dysfunction, the inhibition of NHE-1 has been proposed to attenuate both injuries through its [Ca 2+ ] i -lowering effect (Matsumoto et al, 2004;Luo et al, 2005). Indeed, we previously suggested that sabiporide protects neurons against ischemic injury in vivo and in vitro through its preventing effect on [Ca 2+ ] i overload (Park et al, 2005). In this study, we found that sabiporide can prevent BBB dysfunction in ischemia/hypoxia model in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

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The effect of Na+/H+ exchanger-1 inhibition by sabiporide on blood–brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

2010

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Section: Introductionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

The effect of Na+/H+ exchanger-1 inhibition by sabiporide on blood–brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

2010

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“…In the same model, another selective NHE blocker, sabiporide (3 mg/kg, i.v. 20 min before ischemia), reduced both infarction volume and brain edema by ~40% and had a therapeutic window of 1 hr [99]. EIPA (5 mg/kg, i.p.…”

Section: Pathological Roles For Na + /H + Exchange: Impact On [Na + ]mentioning

confidence: 99%

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Mongin

2007

Pathophysiology

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The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca 2+ overload. The NMDA subtype of glutamate receptors is particularly important as it represents the main initial route for the Ca 2+ influx. High cytoplasmic levels of Ca 2+ activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl − channels and several types of non-channel transporter proteins, such as the Na + ,K + ,2Cl − cotransporter, Na + /H + exchanger, and Na + /Ca 2+ exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long term accumulation of cytoplasmic Ca 2+ . This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.

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“…The NHE-1 inhibitor SM-20220 reduces infarct size in both transient and permanent focal ischemia models (Kuribayashi et al, 1999). Another NHE inhibitor, Sabiporide, reduces infarct size and edema volume when administered before or after ischemia (Park et al, 2005). Our investigations into the role of NHE-1 in cerebral ischemia have used both genetic and pharmacologic inhibition of NHE-1 in a mouse transient middle cerebral artery occlusion model (MCAO).…”

Section: Focal Ischemiamentioning

confidence: 99%

The Na+/H+ Exchanger-1 as a New Molecular Target in Stroke Interventions

Chanana¹,

Sun²,

Ferrazzano³

2012

Advances in the Preclinical Study of Ischemic Stroke

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Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

Cited by 28 publications

References 23 publications

The effect of Na+/H+ exchanger-1 inhibition by sabiporide on blood–brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

The effect of Na+/H+ exchanger-1 inhibition by sabiporide on blood–brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

The Na+/H+ Exchanger-1 as a New Molecular Target in Stroke Interventions

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