% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Hubertus:276804,
      author       = {Hubertus, Vanessa and Meyer, Lea and Waldmann, Lilly and
                      Roolfs, Laurens and Taheri, Nima and Kersting, Katharina and
                      von Bronewski, Emily and Nieminen-Kelhä, Melina and
                      Kremenetskaia, Irina and Uhl, Christian and Fiedler, Kim C
                      and Ode, Jan-Erik and Rex, Andre and Prüß, Harald and
                      Rakhymzhan, Asylkhan and Hauser, Anja E and Niesner, Raluca
                      and Heppner, Frank L and Fehlings, Michael G and Vajkoczy,
                      Peter},
      title        = {{I}dentification of a {T}herapeutic {W}indow for
                      {N}eurovascular {U}nit {R}epair after {E}xperimental
                      {S}pinal {C}ord {I}njury.},
      journal      = {Journal of neurotrauma},
      volume       = {42},
      number       = {3-4},
      issn         = {0897-7151},
      address      = {Larchmont, NY},
      publisher    = {Liebert},
      reportid     = {DZNE-2025-00329},
      pages        = {212 - 228},
      year         = {2025},
      abstract     = {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
                      $50-54\%$ of existing vessels regaining functional
                      perfusion. Longitudinal in vivo 2PM visualized the
                      progressive degeneration of initially preserved spinal cord
                      axons in the peri-traumatic zone after SCI while displaying
                      a rarefication of functionally perfused vessels up to two
                      weeks after injury. Neurobehavioral recovery started after
                      one week but remained impaired over the whole observation
                      period of four weeks after SCI. With this study, a
                      therapeutic window to address the impaired NVU starting from
                      the first days to two weeks after SCI is identified. A
                      number of lines of evidence including in vivo 2PM,
                      assessment of NVU integrity, and neurobehavioral assessments
                      point to the critical nature of targeting the NVU to enhance
                      axonal preservation and regeneration after SCI. Continuous
                      multifactorial therapy applications targeting the integrity
                      of the NVU over the identified therapeutic window of
                      opportunity appears promising to ameliorate functional
                      vessel perseverance and the spinal cord's regenerative
                      capacity.},
      keywords     = {Spinal Cord Injuries: physiopathology / Spinal Cord
                      Injuries: diagnostic imaging / Animals / Mice / Mice, Inbred
                      C57BL / Recovery of Function: physiology / Female / Disease
                      Models, Animal / Magnetic Resonance Imaging / Nerve
                      Regeneration: physiology / Time Factors / neurovascular unit
                      (Other) / spinal cord injury (Other) / spinal cord
                      regeneration (Other) / vascular injury (Other) / vascular
                      regeneration (Other)},
      cin          = {AG Prüß / AG Heppner},
      ddc          = {610},
      cid          = {I:(DE-2719)1810003 / I:(DE-2719)1810007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39585767},
      doi          = {10.1089/neu.2024.0233},
      url          = {https://pub.dzne.de/record/276804},
}