TY  - JOUR
AU  - Hubertus, Vanessa
AU  - Meyer, Lea
AU  - Waldmann, Lilly
AU  - Roolfs, Laurens
AU  - Taheri, Nima
AU  - Kersting, Katharina
AU  - von Bronewski, Emily
AU  - Nieminen-Kelhä, Melina
AU  - Kremenetskaia, Irina
AU  - Uhl, Christian
AU  - Fiedler, Kim C
AU  - Ode, Jan-Erik
AU  - Rex, Andre
AU  - Prüß, Harald
AU  - Rakhymzhan, Asylkhan
AU  - Hauser, Anja E
AU  - Niesner, Raluca
AU  - Heppner, Frank L
AU  - Fehlings, Michael G
AU  - Vajkoczy, Peter
TI  - Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury.
JO  - Journal of neurotrauma
VL  - 42
IS  - 3-4
SN  - 0897-7151
CY  - Larchmont, NY
PB  - Liebert
M1  - DZNE-2025-00329
SP  - 212 - 228
PY  - 2025
AB  - Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal in vivo two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54
KW  - Spinal Cord Injuries: physiopathology
KW  - Spinal Cord Injuries: diagnostic imaging
KW  - Animals
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Recovery of Function: physiology
KW  - Female
KW  - Disease Models, Animal
KW  - Magnetic Resonance Imaging
KW  - Nerve Regeneration: physiology
KW  - Time Factors
KW  - neurovascular unit (Other)
KW  - spinal cord injury (Other)
KW  - spinal cord regeneration (Other)
KW  - vascular injury (Other)
KW  - vascular regeneration (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39585767
DO  - DOI:10.1089/neu.2024.0233
UR  - https://pub.dzne.de/record/276804
ER  -