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

Abstract

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.

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

“…Other treatments failed to completely resolve oedema, although some did significantly attenuate oedema to various degrees. Only one study, Hale et al [31], included an explanation of how they calculated the animal sample size for their study; the rest did not, and only stated the number of animals included. Similarly, 38% of the studies did not report their incomplete data, because the loss of animals was not stated or explained.…”

“…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.…”

“…Abiding by the previously defined inclusion and exclusion criteria, 6525 studies were removed, leaving 16 studies which were deemed eligible for the study and required a full text read. Following the full text screening, two studies were removed because they did not measure spinal cord tissue water content as an outcome measure, therefore 14 studies [3,[20][21][22][23][24][25][26][27][28][29][30][31][32] were included within the study for further analysis. The process of literature identification and sorting strategy is displayed by the PRISMA diagram (Figure 1).…”

“…Alternatively, some utilised more novel therapeutic options, such as melatonin [27,32], and explored re-purposing therapies with known effects on other ailments. In contrast, other studies researched the effectiveness of surgical techniques, for instance, myelotomy [25], or the insertion of a novel implantable osmotic transport device [31]. Furthermore, the treatment follow-up times also varied, ranging from one hour to six weeks.…”

Influence of Anisotropic White Matter on Electroosmotic Flow Induced by Direct Current

“…The primary goals for treating edema with increased ICP are to regulate cerebral perfusion and reduce the ICP. Most existing treatments are non-specific and target towards ameliorating the effect of edema, such as hyperosmolar treatment, neuromuscular blockade, hypothermia, sedation, and decompressive craniectomy (DC) (Walcott et al, 2012;Jha et al, 2019;Hale et al, 2020); most options are accompanied with significant side effects (Li et al, 2013;Jha et al, 2019). Thus, the treatment of cerebral edema is still an arduous task, and new treatment approaches are to be sought.…”