Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats

Li, Ye; Hu, Haiquan; Liu, Jingchen; Zhu, Qingsan; Gu, Rui

doi:10.1590/s0102-865020180020000009

Cited by 5 publications

(10 citation statements)

References 24 publications

(20 reference statements)

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“…Curiously, Cabrera-Aldana et al [17] demonstrated the largest increase in oedema after treatment with methylpredinoslone (MP) (100% above the sham and control group). However, in contrast, Li et al [33] reported 72.2% attenuation after MP treatment at 7 days after SCI. Moreover, Liu et al [27], Ge et al [28] and Li et al [32] reported no significant difference in spinal cord water content or AQP4 expression levels at 12 h, but did show a difference at 24 h after treatment.…”

Section: Results Of Individual Studiesmentioning

confidence: 88%

“…Although each study investigated a different therapeutic, mechanistically, nearly all reported the modulation of AQP4. Not only was downregulation or the subcellular relocalisation of AQP4 a hallmark of an effective oedema treatment, the degree of oedema attenuation determined the extent of functional recovery [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. To complement these findings, the majority of studies also measured locomotor activity, glial activity using GFAP immunoreactivity and visualised the lesion site using IHC or other imaging techniques in an attempt to understand the anti-oedemic action of the novel treatments as well as the complex pathophysiology behind the development of oedema.…”

Section: Discussionmentioning

confidence: 99%

“…They implemented a mixture of pharmaceutical and surgical options each with differing outcome measures. The majority employed pharmacological interventions which involved inhibiting water transport molecules directly, such as TGN-020 or TFP [20,21,30], or indirectly [22][23][24]26,29,33]. Alternatively, some utilised more novel therapeutic options, such as melatonin [27,32], and explored re-purposing therapies with known effects on other ailments.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…For example, nearly all studies reported a downregulation of AQP4 following therapeutic interventions compared to the SCI, coupled with a decrease in GFAP too. In addition, some studies performed locomotor function tests in rats, using a variety of methods, including assessment of BBB [20,21,[23][24][25][26]33] (Table 7). All of the studies showed improvements in locomotor function, including significant improvements in BBB scores after treatment [21,[23][24][25][26].…”

Section: Functional Outcomesmentioning

confidence: 99%

“…Out of the seven studies that assessed locomotor function, five studies used BBB, although measurement time-points ranged from 5 to 28 days [22,[24][25][26]33]. Despite this, we performed a meta-analysis on the pooled data and calculated an overall mean increase of 5.12 in BBB scores after treatment (95%CI 3.12, 7.11; p < 0.00001; I 2 = 97%) (Figure 4).…”

Section: Locomotor Function Improvementsmentioning

confidence: 99%

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Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis

Masterman

Ahmed

2021

Cells

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The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person’s quality of life. There is an unmet clinical need for a treatment which will prevent progression of the injury, allowing improved axonal regeneration and functional recovery to occur. The initial mechanical insult, followed by a cascade of secondary mechanisms, leads to the exacerbation and remodelling of the lesion site, thus inhibiting neurological recovery. Oedema rapidly accumulates following SCI and contributes to the detrimental pathophysiology and worsens functional outcomes. This study systematically reviewed the current experimental treatments being explored in the field of SCI, which specifically target oedema. Abiding by PRISMA guidelines and strict inclusion criteria, 14 studies were identified and analysed from three online databases (PubMed, Web of Science and EMBASE). As a result, we identified three key modalities which attenuate oedema: selective inhibition of the main water channel protein, aquaporin 4 (AQP4), modulation of inflammation and surgical interventions. Collectively, however, they all result in the downregulation of AQP4, which crucially leads to a reduction in oedema and improved functional outcomes. We concluded that trifluoperazine (TFP), a calmodulin kinase inhibitor which prevents the cell-surface localisation of AQP4, was the most efficacious treatment, significantly eliminating oedema within 7 days of administration. To date, this study is the most concise analysis of current experimental treatments for oedema, exposing its molecular mechanisms and assessing potential therapeutic pathways for future research.

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Section: Results Of Individual Studiesmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Functional Outcomesmentioning

confidence: 99%

Section: Locomotor Function Improvementsmentioning

confidence: 99%

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Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis

Masterman

Ahmed

2021

Cells

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Aquaporin 4 and its Relationship with Brain Astrocytomas – Literature Review

Vieira

Farias

Peres

et al. 2023

Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery

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Background Aquaporins (AQPs) are a family of membrane proteins that regulate the osmotic permeability of the plasma membrane. There are described in the literature a total of 13 types of Aquaporins in mammals, each with different places of expression. In addition to water, some AQPs allow the passage of glycerol and ammonia, being called Aquaglyceroproteins. In the central nervous system, AQPs 1 and 4 are expressed, being responsible for the water regulation in the blood-brain barrier. These two AQPs are believed to participate in the pathophysiological process that governs the behavior of various CNS diseases, such as trauma and primary tumors. More particularly, there are quite controversial data in the literature on the expression of AQP4 in tumors and its relationship with disease progression and treatment possibility. Objective This paper aims to perform a literature review on the function and expression of AQP4 in the CNS and primary tumors of this system, to compile what is in the literature on the subject and raise new possible research hypotheses. Methods The PUBMED platform was used for bibliographic survey using “Aquaporin 4,” “expression” and “astrocytomas” as keywords. Articles older than 2008 and articles that did not address AQP4 expression in astrocytomas were excluded. In the selected articles, the following topics were investigated: AQP4 structure, brain and tumor localization, and relationship with peritumoral edema. Results Regarding the structure and location of AQP4, the literature presents two isoforms of AQP4: M1 and M23. Both form clusters of AQP4 called “orthogonal arrays of proteins - OAPs.” In the tumor tissue, the literature shows a decrease in the formation of OAPs and an increase in the expression of both AQP4 isoforms, besides losing their polarity, diffusing through the cytoplasmic membrane. As for the function of AQP4 in tumors, AQP4 assists in cell migration and invasion, in addition to participating in cell proliferation and apoptosis. Regarding the relationship with cerebral edema, there are controversial knowledge. Studies have shown that increased AQP4 aggravates cytotoxic edema of tumor cells and, by assisting in cell migration and angiogenesis, indirectly assist in the formation of vasogenic edema by breaking the blood-brain barrier. Other studies, however, point to the increase in AQP4 as a protective mechanism to combat vasogenic edema that occurs in tumor formation. Furthermore, the literature presents a therapeutic proposal in which, by inhibiting AQP4 expression, tumor migration and cerebral edema decrease in rats with glioblastoma. Discussion As shown in the literature, there is a difference in histopathological structure between high and low grade gliomas. However, there are common changes between them. These common changes could then be used as a factor of severity or evolution of low-grade to high-grade tumors. Moreover, it is not yet possible to perceive the true relationship of AQP4 expression and increased VEGF evolution of peritumoral edema. Finally, it can be hypothesized that since the expression ratio between AQP4 isoforms in normal tissue is greater than in some tumors, the decrease in this ratio is due either to decreased M23 expression or increased of the isoform M1. Conclusion Further studies are needed to understand the physiology and pathophysiology involving AQP4 in astrocytomas to create effective therapeutic proposals to combat this disease.

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Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury

Fischer,

Bättig,

Stienen

et al. 2024

Front. Neurosci.

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Traumatic spinal cord injuries (SCIs) continue to be a major healthcare concern, with a rising prevalence worldwide. In response to this growing medical challenge, considerable scientific attention has been devoted to developing neuroprotective and neuroregenerative strategies aimed at improving the prognosis and quality of life for individuals with SCIs. This comprehensive review aims to provide an up-to-date and thorough overview of the latest neuroregenerative and neuroprotective therapies currently under investigation. These strategies encompass a multifaceted approach that include neuropharmacological interventions, cell-based therapies, and other promising strategies such as biomaterial scaffolds and neuro-modulation therapies. In addition, the review discusses the importance of acute clinical management, including the role of hemodynamic management as well as timing and technical aspects of surgery as key factors mitigating the secondary injury following SCI. In conclusion, this review underscores the ongoing scientific efforts to enhance patient outcomes and quality of life, focusing on upcoming strategies for the management of traumatic SCI. Each section provides a working knowledge of the fundamental preclinical and patient trials relevant to clinicians while underscoring the pathophysiologic rationale for the therapies.

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Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats

Cited by 5 publications

References 24 publications

Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis

Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis

Aquaporin 4 and its Relationship with Brain Astrocytomas – Literature Review

Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury

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