{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:02:28Z","timestamp":1785132148906,"version":"3.55.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"9-10","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Contusive and compressive spinal cord injury (SCI) induces pathological changes to spinal cord white matter (WM) including periaxonal swelling and resultant disruption of the axomyelinic interface, axonal swelling\/spheroid formation, and secondary axonal transection. To further our knowledge of the role of vascular edema in these pathological changes to WM, we designed, and three-dimensional (3D) printed a dual-compartment imaging chamber separated by a semipermeable membrane to mimic and manipulate interstitial and vascular fluid compartments in real time. We hypothesized that hypertonic saline (HTS) applied to the \u201cvascular\u201d chamber would osmotically shift fluid out of the periaxonal space and preserve myelinated fibers after SCI. Adult male and female 6- to 8-week-old\n                    <jats:italic toggle=\"yes\">Thy1<\/jats:italic>\n                    <jats:sup>YFP+<\/jats:sup>\n                    transgenic mice underwent a C5, mild contusive SCI (30 kilodyne, IH Impactor)\n                    <jats:italic toggle=\"yes\">in\u00a0vivo,<\/jats:italic>\n                    and their spinal cords were harvested for\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    imaging. Utilizing longitudinal two-photon excitation microscopy (2PE), we imaged both myelin (Nile red) and axons (YFP+) simultaneously up to 4 h after SCI. C5 contusive SCI conditions induced significant increases in periaxonal swelling and axonal spheroid formation within the dorsal column fibers over time. In contrast, perfusion of 3% and 5% HTS in the \u201cvascular\u201d compartment beginning 30 min after SCI was highly protective and significantly reduced periaxonal swelling and axonal spheroid formation from 1 h 30 min to the last hour recorded (4 h post-SCI) compared to normal saline (NS) controls. At 2 post-SCI, treatment with 3% and 5% HTS significantly (Kruskal\u2013Wallis ANOVA on Ranks,\n                    <jats:italic toggle=\"yes\">H<\/jats:italic>\n                    (3) = 3,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.05,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 5\u20136\/group) reduced periaxonal swelling compared to NS (median, 25th percentile; 11.00, 4.00\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    9.00, 7.00\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    48.00, 29.50, respectively; Dunn\u2019s method, both\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). By 4 h post-SCI, treatment with 3% and 5% HTS significantly (\n                    <jats:italic toggle=\"yes\">H<\/jats:italic>\n                    (3) = 15.74,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.001,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 5\u20136\/group) decreased axonal spheroids compared to NS (5.00, 3.00\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    4.00, 3.00\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    95.00, 38.75,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.001,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001, respectively). In contrast, 7.5% HTS had no beneficial effect. Collectively, these data provide insight into the dynamic interplay between interstitial fluid exchange within the periaxonal space and pathological changes in myelinated fibers following SCI. Delayed\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    administration of 3% HTS significantly increased axonal survival and reduced periaxonal swellings 24 h post SCI compared to NS control, validating the translatability of our dual compartment imaging chamber (mean, standard deviation; 58.09, 3.34\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    32.08, 5.98,\n                    <jats:italic toggle=\"yes\">p =<\/jats:italic>\n                    0.003; 595.19, 326.10\n                    <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                    1525.25, 259.82,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.018, respectively). Our findings suggest that low-dose hypertonic solutions may have a protective effect in part by mitigating periaxonal swelling and thereby potentially reducing the occurrence of axonal spheroids within these denuded regions. These results enhance understanding of secondary axonal degeneration mechanisms and hold promise for targeted therapeutic interventions to improve outcomes in SCI.\n                  <\/jats:p>","DOI":"10.1089\/neu.2024.0454","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T03:07:21Z","timestamp":1741230441000},"page":"704-714","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Three-Dimensional Design and Implementation of a Dual Compartment Imaging Chamber to Assess Effects of Hypertonic Saline on Periaxonal Swelling and Axonal Spheroid Formation Following Cervical Contusive Spinal Cord Injury in Real Time"],"prefix":"10.1177","volume":"43","author":[{"given":"Francisco","family":"Cortez-Thomas","sequence":"first","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, Kentucky, USA."},{"name":"Bioengineering, School of Medicine, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer O.","family":"Ames","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarayu","family":"Alli","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Jones","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-8991","authenticated-orcid":false,"given":"David P.","family":"Stirling","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, Kentucky, USA."},{"name":"Departments of Neurological Surgery, School of Medicine, University of Louisville, Louisville, Kentucky, USA."},{"name":"Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200109000-00002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2021.03.002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2003.07.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105123"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6683"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30138-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087159"},{"issue":"0","key":"e_1_3_3_9_2","first-page":"440","article-title":"Edema formation and central hemorrhagic necrosis following impact injury to primate spinal cord","volume":"25","author":"Goodman JH","year":"1974","unstructured":"Goodman JH, , Bingham WGJr, , Hunt WE. 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