Expression of water channel aquaporin-4 during experimental syringomyelia

Aghayev, Kamran; Bal, Ercan; Rahimli, Tural; Mut, Melike; Balcı, Serdar; Vrionis, Frank D.; Akalan, Nejat

doi:10.3171/2011.5.spine10303

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…The central canal expands on either side of these occlusions, producing an ependyma-lined syrinx. 37 This model differs from the intracisternal kaolin model of syringomyelia used in the studies by Aghayev et al, 1 in that it produces dilation of the central canal without communication with the fourth ventricle. 37 The intracisternal kaolin model produces ventricular enlargement, resulting in raised intracranial pressure, as well as dilation of the central canal.…”

Section: Animal Modelmentioning

confidence: 97%

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Aquaporin-4 expression and blood–spinal cord barrier permeability in canalicular syringomyelia

Hemley

Bilston

Stoodley

2012

SPI

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Object Noncommunicating canalicular syringomyelia occurs in up to 65% of patients with Chiari malformation Type I. The pathogenesis of this type of syringomyelia is poorly understood and treatment is not always effective. Although it is generally thought that syringomyelia is simply an accumulation of CSF from the subarachnoid space, the pathogenesis is likely to be more complex and may involve cellular and molecular processes. Aquaporin-4 (AQP4) has been implicated in numerous CNS pathological conditions involving fluid accumulation, including spinal cord edema. There is evidence that AQP4 facilitates the removal of extracellular water following vasogenic edema. The aim of this study was to investigate AQP4 expression and the structural and functional integrity of the blood–spinal cord barrier (BSCB) in a model of noncommunicating canalicular syringomyelia. Methods A kaolin-induced model of canalicular syringomyelia was used to investigate BSCB permeability and AQP4 expression in 27 adult male Sprague-Dawley rats. Control groups consisted of nonoperated, laminectomy-only, and saline-injected animals. The structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen. Functional integrity of the BSCB was assessed by extravasation of systemically injected horseradish peroxidase (HRP) at 1, 3, 6, or 12 weeks after surgery. Immunofluorescence was used to assess AQP4 and glial fibrillary acidic protein (GFAP) expression at 12 weeks following syrinx induction. Results Extravasation of HRP was evident surrounding the central canal in 11 of 15 animals injected with kaolin, and in 2 of the 5 sham-injected animals. No disruption of the BSCB was observed in laminectomy-only controls. At 12 weeks the tracer leakage was widespread, occurring at every level rostral to the kaolin injection. At this time point there was a decrease in EBA expression in the gray matter surrounding the central canal from C-5 to C-7. Aquaporin-4 was expressed in gray- and white-matter astrocytes, predominantly at the glia limitans interna and externa, and to a lesser extent around neurons and blood vessels, in both control and syrinx animals. Expression of GFAP and APQ4 directly surrounding the central canal in kaolin-injected animals was variable and not significantly different from expression in controls. Conclusions This study demonstrated a prolonged disruption of the BSCB directly surrounding the central canal in the experimental model of noncommunicating canalicular syringomyelia. The disruption was widespread at 12 weeks, when central canal dilation was most marked. Loss of integrity of the barrier with fluid entering the interstitial space of the spinal parenchyma may contribute to enlargement of the canal and progression of syringomyelia. Significant changes in AQP4 expression were not observed in this model of canalicular syringomyelia. Further investigation is needed to elucidate whether subtle changes in AQP4 expression occur in canalicular syringomyelia.

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Section: Animal Modelmentioning

confidence: 97%

“…44 Recent studies have investigated AQP4 changes in a model of communicating canalicular syringomyelia. 1,58 To the best of our knowledge, the study reported here is the first to look at AQP4 expression in noncommunicating canalicular syringomyelia.…”

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confidence: 90%

Aquaporin-4 expression and blood–spinal cord barrier permeability in canalicular syringomyelia

Hemley

Bilston

Stoodley

2012

SPI

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“…Nonsurgical treatments are needed to overcome the risks and challenges of current therapeutic interventions. Unfortunately, there is a poor understanding of the basis for SM [ 30 ], and in response, the molecular aspects of SM have been a recent research focus in the field [ 12 – 15 ]. These studies provide a solid foundation for the development of non-surgical treatments for SM; because it is important to establish further analytical tools, particularly those that monitor functional outcomes over time to evaluate treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple competing theoretical mechanisms have attempted to explain syrinx formation/expansion [ 7 – 11 ]. More recent work, including our own, has explored molecular aspects of SM to attempt to better understand the connections to SM pathology [ 12 – 16 ] while also extending this to animal PTSM models [ 10 , 15 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of locomotion deficit in a post-traumatic syringomyelia rat model using automated gait analysis technique

2021

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Syringomyelia (SM) is a spinal cord disorder in which a cyst (syrinx) filled with fluid forms in the spinal cord post-injury/disease, in patients syrinx symptoms include loss of pain and temperature sensation or locomotion deficit. Currently, there are no small animal models and connected tools to help study the functional impacts of SM. The objective of this study was to determine the detectability of subtle locomotion deficits due to syrinx formation/expansion in post-traumatic syringomyelia (PTSM) rat model using the recently reported method of Gait Analysis Instrumentation, and Technology Optimized for Rodents (GAITOR) with Automated Gait Analysis Through Hues and Areas (AGATHA) technique. First videos of the rats were collected while walking in an arena (using GAITOR) followed by extracting meaningful locomotion information from collected videos using AGATHA protocol. PTSM injured rats demonstrated detectable locomotion deficits in terms of duty factor imbalance, paw placement accuracy, step contact width, stride length, and phase dispersion parameters compared to uninjured rats due to SM. We concluded that this technique could detect mild and subtle locomotion deficits associated with PTSM injury, which also in future work could be used further to monitor locomotion responses after different treatment strategies for SM.

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“…However, no effective results were obtained 4 hours after the treatment. Early intervention could be more effective before the onset of cytotoxic edema at a very early period within hours after the trauma (1,2,3,8,20,21,29). Therefore, the modification of the antisense dose or a change in time intervals of administration may be considered.…”

mentioning

confidence: 99%

Suppression of aquaporin-4 by antisense oligonucleotides reduces brain edema in experimental traumatic brain injury

Hekimoğlu¹,

Lüle²,

Özer³

et al. 2021

Turkish Neurosurgery

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AIM:To investigate the suppression of aquaporin-4 (AQP4) synthesis through intracerebroventricular (i.c.v.) injection of antisense oligonucleotide after focal cortical contusion injury in mice. MATERIAL and METHODS:This study used 12-week-old female Swiss albino mice (weight, 20-25 g) to create a focal cortical contusion model by the weight-drop method (35 g blunt weight, 70 cm height) onto the parietal cortex after craniectomy. The sham group underwent craniectomy without trauma. In the control group, weight was dropped onto the parietal cortex immediately after i.c.v. injection of Dulbecco's Modified Eagle Medium after craniectomy. In addition, 1 nM of aquaporin-4 (AQP4) antisense oligonucleotide (ASO) was injected via the i.c.v. route immediately after trauma (0 hour) and 4 hours after trauma. All animals underwent magnetic resonance (MR) imaging and were sacrificed at 24 hours. The brain-water content was determined using the wet/dry weight method. RESULTS:In the sham group, the average percentage of the brain-water content was 77.75% compared with the control group with 79.87%, and the difference was significant (p=0.017). The average was 78.81% and significantly reduced in the therapy group compared with the control group (p=0.026) at 0 hour. In the 4-hour treatment group, the average of 79.11% was not significant (p=0.39). MR imaging findings also showed a substantial reduction in brain edema in the 0-h treatment group. However, the 4-h treatment results, when compared with the control trauma group, did not show a significant difference. CONCLUSION:This study demonstrated that AQP4-ASO therapy, when administered early after diffuse traumatic brain injury, leads to a significant reduction in brain edema.

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Expression of water channel aquaporin-4 during experimental syringomyelia

Cited by 9 publications

References 33 publications

Aquaporin-4 expression and blood–spinal cord barrier permeability in canalicular syringomyelia

Aquaporin-4 expression and blood–spinal cord barrier permeability in canalicular syringomyelia

Detection of locomotion deficit in a post-traumatic syringomyelia rat model using automated gait analysis technique

Suppression of aquaporin-4 by antisense oligonucleotides reduces brain edema in experimental traumatic brain injury

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