Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema

Taya, Keisuke; Gülşen, Salih; Okuno, Kenji; Prieto, R.; Marmarou, Christina R.; Marmarou, Anthony

doi:10.1007/978-3-211-85578-2_83

Cited by 43 publications

(57 citation statements)

References 30 publications

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“…30 Overall, we showed that V1aR inhibition decreases brain AQP4 expression, brain edema, and astrocytic cell swelling, and reduces expression of V1aR. 30,40 Importantly, these studies showed a clear correlation between the time course of the traumainduced shift in intracerebral Na + concentrations and the increase in percent brain water content. 22,30,31,39,41 Our findings were consistent with previous reports demonstrating similar shifts between water and Na + content.…”

Section: Introductionmentioning

confidence: 71%

“…Further, experimental models of intracerebral hemorrhage, middle cerebral artery occlusion, ischemia, and cold and traumatic brain injury have demonstrated that V1aR inhibition reduces brain edema. [22][23][24][25][26][27][28][29][30][31] The underlying mechanism of this response has been attributed to either modulation of vasopressin in the brain parenchyma 17 or its interaction with aquaporin-4 (AQP4). AQP4 is the predominant water channel in the brain and has a significant role in the pathophysiology of brain edema.…”

Section: Introductionmentioning

confidence: 99%

“…[32][33][34][35][36] Evidence suggests V1aR regulate the expression and function of AQP4, 17,22,37 although the mechanism is still elusive. 17,22,[29][30][31] Recently, we explored the hypothesis that selective V1aR inhibition by the non-peptide antagonist SR49059 30,38 can reduce brain edema in animal models of middle cerebral artery occlusion 22,39 and TBI. 30 Overall, we showed that V1aR inhibition decreases brain AQP4 expression, brain edema, and astrocytic cell swelling, and reduces expression of V1aR.…”

Section: Introductionmentioning

confidence: 99%

“…17,22,[29][30][31] Recently, we explored the hypothesis that selective V1aR inhibition by the non-peptide antagonist SR49059 30,38 can reduce brain edema in animal models of middle cerebral artery occlusion 22,39 and TBI. 30 Overall, we showed that V1aR inhibition decreases brain AQP4 expression, brain edema, and astrocytic cell swelling, and reduces expression of V1aR. 30,40 Importantly, these studies showed a clear correlation between the time course of the traumainduced shift in intracerebral Na + concentrations and the increase in percent brain water content.…”

Section: Introductionmentioning

confidence: 99%

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Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

Filippidis

Liang²,

Wang³

et al. 2014

Journal of Neurotrauma

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Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na. Ion-selective Na + and K + electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na + ] e , [K + ] e , and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na + ] e to 80.1 -15 and 87.9 -7.9 mM and increase in [K + ] e to 20.9 -3.8 and 13.4 -3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p < 0.001 vs. baseline; ns between groups). Importantly, [Na + ] e in CCI-SR49059-ISE was reduced 5-20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na + ] e recovery. In contrast, [K + ] e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na + ] e recovery and reduced ICP. By augmenting the [Na + ] e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI.

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

Filippidis

Liang²,

Wang³

et al. 2014

Journal of Neurotrauma

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“…Aquaporins (AQPs) are integral membrane proteins that form pores in membranes of mammalian cells, and play an important role in development and resolution of cerebral edema (Pasantes-Morales & Cruz-Rangel 2010). AQPs modulation offers a potential therapeutic intervention to prevent or treat brain swelling (Manley et al 2000;Papadopoulos & Verkman 2008;Taya et al 2008). Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases involved in the process of tissue remodeling following brain injury from stroke or trauma.…”

Section: Pharmacotherapymentioning

confidence: 99%

Traumatic Brain Injury - Acute Care

Hays¹,

Varma²

2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

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Role of vasopressin and its antagonism in stroke related edema

Ameli

Gubernick

et al. 2014

J of Neuroscience Research

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Although many approaches have been tried in the attempt to reduce the devastating impact of stroke, tissue plasminogen activator for thromboembolic stroke is the only proved, effective acute stroke treatment to date. Vasopressin, an acute-phase reactant, is released after brain injury and is partially responsible for the subsequent inflammatory response via activation of divergent pathways. Recently there has been increasing interest in vasopressin because it is implicated in inflammation, cerebral edema, increased intracerebral pressure, and cerebral ion and neurotransmitter dysfunctions after cerebral ischemia. Additionally, copeptin, a byproduct of vasopressin production, may serve as a promising independent marker of tissue damage and prognosis after stroke, thereby corroborating the role of vasopressin in acute brain injury. Thus, vasopressin antagonists have a potential role in early stroke intervention, an effect thought to be mediated via interactions with aquaporin receptors, specifically aquaporin-4. Despite some ambiguity, vasopressin V1a receptor antagonism has been consistently associated with attenuated secondary brain injury and edema in experimental stroke models. The role of the vasopressin V2 receptor remains unclear, but perhaps it is involved in a positive feedback loop for vasopressin expression. Despite the encouraging initial findings we report here, future research is required to characterize further the utility of vasopressin antagonists in treatment of stroke.

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Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema

Cited by 43 publications

References 30 publications

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

Traumatic Brain Injury - Acute Care

Role of vasopressin and its antagonism in stroke related edema

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