Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice

McBride, Devin W.; Donovan, Virginia; Hsu, Mike S.; Obenaus, André; Rodgers, V.G.J.; Binder, Devin K.

doi:10.1007/978-3-319-18497-5_49

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…It has been demonstrated that, through establishing an external osmotic gradient, water can be removed from the brain in a controlled manner under normal and pathological brain swelling conditions. Such an “osmotic treatment device” (OTD) was able to reduce brain tissue water content and improve neurological outcome in mouse models of cytotoxic edema and traumatic brain injury without causing histological damage [ 118 , 119 , 120 ]. These results established proof-of-principle for the concept of direct osmotherapy for the treatment of CNS edema.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

The Role of Aquaporins in Spinal Cord Injury

Garcia

Jonak

Binder

2023

Cells

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Edema formation following traumatic spinal cord injury (SCI) exacerbates secondary injury, and the severity of edema correlates with worse neurological outcome in human patients. To date, there are no effective treatments to directly resolve edema within the spinal cord. The aquaporin-4 (AQP4) water channel is found on plasma membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid, and ependyma around the central canal. Local expression at these tissue–fluid interfaces allows AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma. In this review, we consider the available evidence regarding the potential role of AQP4 in edema after SCI. Although more work remains to be carried out, the overall evidence indicates a critical role for AQP4 channels in edema formation and resolution following SCI and the therapeutic potential of AQP4 modulation in edema resolution and functional recovery. Further work to elucidate the expression and subcellular localization of AQP4 during specific phases after SCI will inform the therapeutic modulation of AQP4 for the optimization of histological and neurological outcomes.

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Section: Summary and Future Directionsmentioning

confidence: 99%

The Role of Aquaporins in Spinal Cord Injury

Garcia

Jonak

Binder

2023

Cells

Self Cite

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“…We have recently demonstrated that through establishing an external osmotic gradient, water can be removed from the brain in a controlled manner under normal and pathological brain swelling conditions. We found that the OTD reduced tissue water content and dramatically improved neurological outcome in an acute mouse models of cytotoxic edema and traumatic brain injury (TBI induced by controlled cortical impact, CCI) without causing histological damage ( McBride et al, 2012 , 2014 , 2016 ). These results established proof-of-principle for the concept of direct osmotherapy for treatment of CNS edema.…”

Section: Introductionmentioning

confidence: 97%

“…There is, therefore, a need for new methods to effectively ameliorate edema following SCI in order to minimize spinal cord compression, decrease ISP at the injury site, improve vascular perfusion (SCPP), and improve neurological outcome. In this work we develop our currently effective osmotic transport device (OTD) that has been shown to improve outcome in global and focal models of cerebral edema ( McBride et al, 2012 , 2014 , 2016 ) and apply it to SCI in a well-accepted rodent model of thoracic contusion SCI.…”

Section: Introductionmentioning

confidence: 99%

Implantable Osmotic Transport Device Can Reduce Edema After Severe Contusion Spinal Cord Injury

Hale

Yonan

Batarseh

et al. 2020

Front. Bioeng. Biotechnol.

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Recent findings from the ISCoPe study indicate that, after severe contusion to the spinal cord, edema originating in the spinal cord accumulates and compresses the tissue against the surrounding dura mater, despite decompressive laminectomy. It is hypothesized that this compression results in restricted flow of cerebrospinal fluid (CSF) in the subarachnoid space and central canal and ultimately collapses local vasculature, exacerbating ischemia and secondary injury. Here we developed a surgically mounted osmotic transport device (OTD) that rests on the dura and can osmotically remove excess fluid at the injury site. Tests were performed in 4-h studies immediately following severe (250 kD) contusion at T8 in rats using the OTD. A 3-h treatment with the OTD after 1-h post injury significantly reduced spinal cord edema compared to injured controls. A first approximation mathematical interpretation implies that this modest reduction in edema may be significant enough to relieve compression of local vasculature and restore flow of CSF in the region. In addition, we determined the progression of edema up to 28 days after insult in the rat for the same injury model. Results showed peak edema at 72 h. These preliminary results suggest that incorporating the OTD to operate continuously at the site of injury throughout the critical period of edema progression, the device may significantly improve recovery following contusion spinal cord injury.

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Differential densimetry: A method for determining ultra-low fluid flux and tissue permeability

et al. 2019

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Osmotic transport devices (OTDs) are forward osmosis membrane devices that we recently developed to remove accumulated fluid from swollen tissue, in-vivo, under severe conditions. As such, the relative volume of the fluid required to be removed and the volumetric flowrate may be two orders of magnitude less than the operating volume and tangential flowrate of the device. This makes it challenging to measure the rate of fluid flow from the swollen tissue. Here, we introduce a differential densimetry method for determining ultra-low volumetric flux through tissue samples. This technique uses two vibrating tube density sensors, one placed upstream of the membrane in contact with the tissue sample, and one placed downstream. Any flow of biological fluid withdrawn through the tissue will combine with the OTD operating fluid resulting in an observed density shift in the second density sensor. By measuring the difference in density between the upstream and downstream fluids, one can calculate the amount of fluid flowing across the tissue with a relatively high level of sensitivity. This method is also relatively insensitive to drift from temperature fluctuations and capable of continuously monitoring tissue permeability in real time. As a proof of concept, we used this technique to measure fluid flow across ex-vivo rat spinal tissue for an appropriately scaled OTD. The repeatability error had a maximum of only 12%. This implies that this method can provide highly acceptable flux measurements with reasonable reproducibility in real-time applications of fluid removal in-vivo.

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Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice

Cited by 3 publications

References 16 publications

The Role of Aquaporins in Spinal Cord Injury

The Role of Aquaporins in Spinal Cord Injury

Implantable Osmotic Transport Device Can Reduce Edema After Severe Contusion Spinal Cord Injury

Differential densimetry: A method for determining ultra-low fluid flux and tissue permeability

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