Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema

Igarashi, Hironaka; Huber, Vincent J.; Teräs, Mika; Nakada, Tsutomu

doi:10.1007/s10072-010-0431-1

Cited by 138 publications

(112 citation statements)

References 19 publications

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“…The role of AQPs in brain water balance received much attention recently (32). AQPs are membrane proteins responsible for cellular water permeability.…”

Section: Discussionmentioning

confidence: 99%

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model*

Liu

Li²,

Luo³

et al. 2011

Critical Care Medicine

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“…The role of AQPs in brain water balance received much attention recently (32). AQPs are membrane proteins responsible for cellular water permeability.…”

Section: Discussionmentioning

confidence: 99%

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model*

Liu

Li²,

Luo³

et al. 2011

Critical Care Medicine

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“…Inhibitors of AQP-4 and MMP-9 may protect the BBB to a certain extent (20). The extent of brain edema observed in cerebral ischemia/reperfusion animals was significantly reduced following inhibition, and the animals demonstrated an improved prognosis (21)(22)(23). These results indicated that the mechanism underlying BBB protection may be associated with the inhibition of AQP-4 and MMP-9 function.…”

Section: Discussionmentioning

confidence: 84%

Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury

Liang

Miao

et al. 2015

Molecular Medicine Reports

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Abstract. Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by ischemic stroke, protects the brain from ischemia/reperfusion injury and improves neuronal function. However, whether propofol is able to protect the blood brain barrier (BBB) and the underlying mechanisms have remained to be elucidated. In the present study, a rat model of cerebral ischemia/reperfusion was established, using a thread embolism to achieve middle cerebral artery occlusion. Rats were treated with propofol (propofol post-conditioning) or physiological saline (control) administered by intravenous injection 30 min following reperfusion. Twenty-four hours following reperfusion, neurobehavioral manifestations were assessed. The levels of cephaloedema, damage to the BBB and expression levels of matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun N-terminal kinase (pJNK) were determined in order to evaluate the effects of propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group, the levels of brain water content and Evans blue content, as well as the expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the propofol post-conditioning group. These results indicated that propofol post-conditioning improved the neurobehavioral manifestations and attenuated the BBB damage and cephaloedema induced following cerebral ischemia/reperfusion. This effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the concurrent decrease in JNK phosphorylation.

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“…This group further identified a novel aquaporin-4 inhibitor called 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020). In a brain ischemic model, they found significant reductions in the cerebral edema and cortical infarction size in the pretreated mice [54]. …”

Section: Aquaporin-4 As a Therapeutic Target In Cerebral Edemamentioning

confidence: 99%

Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema

Tang

Yang

2016

IJMS

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Aquaporin-4 (AQP4) is a family member of water-channel proteins and is dominantly expressed in the foot process of glial cells surrounding capillaries. The predominant expression at the boundaries between cerebral parenchyma and major fluid compartments suggests the function of aquaporin-4 in water transfer into and out of the brain parenchyma. Accumulating evidences have suggested that the dysregulation of aquaporin-4 relates to the brain edema resulting from a variety of neuro-disorders, such as ischemic or hemorrhagic stroke, trauma, etc. During edema formation in the brain, aquaporin-4 has been shown to contribute to the astrocytic swelling, while in the resolution phase, it has been seen to facilitate the reabsorption of extracellular fluid. In addition, aquaporin-4-deficient mice are protected from cytotoxic edema produced by water intoxication and brain ischemia. However, aquaporin-4 deletion exacerbates vasogenic edema in the brain of different pathological disorders. Recently, our published data showed that the upregulation of aquaporin-4 in astrocytes probably contributes to the transition from cytotoxic edema to vasogenic edema. In this review, apart from the traditional knowledge, we also introduce our latest findings about the effects of mesenchymal stem cells (MSCs) and microRNA-29b on aquaporin-4, which could provide powerful intervention tools targeting aquaporin-4.

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Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema

Cited by 138 publications

References 19 publications

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model*

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model*

Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury

Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema

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