Modulation of Na+/K+- ATPase activity by triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice

Della-Pace, Iuri Domingues; Souza, Thaíze Lopes de; Grauncke, Ana Claudia Beck; Rambo, Leonardo Magno; Ribeiro, Leandro Rodrigo; Cipolatto, Rafael Parcianello; Severo, Leandro; Papalia, Willian Link; Santos, Adair R.S.; Facundo, Valdir Alves; Oliveira, Mauro Schneider; Furian, Ana Flávia; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

doi:10.1016/j.ejphar.2019.02.040

Cited by 8 publications

(3 citation statements)

References 18 publications

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“… 7 , 8 Mutations in CACNA1A or Na+/K+ ATPase, for example, can cause life-threatening brain swelling in response to trivial head injuries. 9 , 10 The present study is the first step toward identifying common genetic variants that modulate a person's response to TBI. Such variants offer the promise of yielding novel targets for desperately needed therapies that could dampen the “dose” of neurotrauma, or improve the trajectory of recovery and ultimate functional outcome.…”

Section: Introductionmentioning

confidence: 99%

A genome-wide association study of outcome from traumatic brain injury

et al. 2022

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Section: Introductionmentioning

confidence: 99%

A genome-wide association study of outcome from traumatic brain injury

et al. 2022

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“…With compromised NKA function unable to balance these transport processes, Na + i accumulation worsens, causing EC swelling [ 16 ], damaging BBB integrity and leading to brain edema in stroke brains [ 72 ]. Similarly, persistent decrease in NKA activity is observed in various traumatic brain injury (TBI) models, contributing to BBB damage [ 73 , 74 ]. Dysfunctional NKA activity and intracellular Na + accumulation has been associated with neuroaxonal loss in multiple sclerosis patients [ 75 ], sustained membrane depolarization and NMDA receptor overactivation and excitotoxicity in Huntington’s disease (HD) [ 76 ].…”

Section: Key Ion Transporters and Channels At The Bbbmentioning

confidence: 99%

Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer’s Disease and Vascular Dementia

2024

Aging dis

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The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism and neuronal function. Regulation of nutrient, water, and ion transport across the BBB is tightly controlled by specialized ion transporters and channels located within its unique cellular components. These dynamic transport processes not only influence the BBB’s structure but also impact vital signaling mechanisms, essential for its optimal function. Disruption in ion, pH, and fluid balance at the BBB is associated with brain pathology and has been implicated in various neurological conditions, including stroke, epilepsy, trauma, and neurodegenerative diseases such as Alzheimer’s disease (AD). However, knowledge gaps exist regarding the impact of ion transport dysregulation on BBB function in neurodegenerative dementias. Several factors contribute to this gap: the complex nature of these conditions, historical research focus on neuronal mechanisms and technical challenges in studying the ion transport mechanisms in in vivo models and the lack of efficient in vitro BBB dementia models. This review provides an overview of current research on the roles of ion transporters and channels at the BBB and poses specific research questions: 1) How are the expression and activity of key ion transporters altered in AD and vascular dementia (VaD); 2) Do these changes contribute to BBB dysfunction and disease progression; and 3) Can restoring ion transport function mitigate BBB dysfunction and improve clinical outcomes. Addressing these gaps will provide a greater insight into the vascular pathology of neurodegenerative disorders.

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“…It possesses an anti-convulsant effect. The protective effect of TTHL is presented by the induction of glutamatergic maintenance, possibly by the interaction with NMDA and the inhibition of protein kinase-C-mediated phosphorylation of the Na+/K+-ATPase-α1 subunit [ 177 ].…”

Section: Novel Pharmacologic Strategies For Tbi: From Experimental To...mentioning

confidence: 99%

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

Battaglini

Siwicka-Gieroba

Rocco

et al. 2021

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: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

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Modulation of Na+/K+- ATPase activity by triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice

Cited by 8 publications

References 18 publications

A genome-wide association study of outcome from traumatic brain injury

A genome-wide association study of outcome from traumatic brain injury

Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer’s Disease and Vascular Dementia

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

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