Characterization of vascular disruption and blood-spinal cord barrier permeability following traumatic spinal cord injury.

Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. Spectrophotometry of EB tissue showed maximal BSCB disruption at 24 h postinjury, with significant disruption observed until 5 days postinjury (p<0.01). FITC-LEA-identified functional vasculature was dramatically reduced by 24 h. Similarly, RECA-1 immunohistochemistry showed a significant decrease in the number of vessels at 24 h postinjury, compared to uninjured animals (p<0.01), with slight increases in endogenous revascularization by 10 days postinjury. White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI.

Effects of adult neural precursor-derived myelination on axonal function in the perinatal congenitally dysmyelinated brain: optimizing time of intervention, developing accurate prediction models, and enhancing performance.

Stem cell repair shows substantial translational potential for neurological injury, but the mechanisms of action remain unclear. This study aimed to investigate whether transplanted stem cells could induce comprehensive functional remyelination. Subventricular zone (SVZ)-derived adult neural precursor cells (aNPCs) were injected bilaterally into major cerebral white matter tracts of myelin-deficient shiverer mice on postnatal day (P) 0, P7, and P21. Tripotential NPCs, when transplanted in vivo, integrated anatomically and functionally into local white matter and preferentially became Olig2+, Myelin Associated Glycoprotein-positive, Myelin Basic Protein-positive oligodendrocytes, rather than Glial Fibrillary Acidic Protein-positive astrocytes or Neurofiliment 200-positive neurons. Processes interacted with axons and transmission electron microscopy showed multilamellar axonal ensheathment. Nodal architecture was restored and by quantifying these anatomical parameters a computer model was generated that accurately predicted action potential velocity, determined by ex vivo slice recordings. Although there was no obvious phenotypic improvement in transplanted shi/shis, myelinated axons exhibited faster conduction, lower activation threshold, less refractoriness, and improved response to high-frequency stimulation than dysmyelinated counterparts. Furthermore, they showed improved resilience to ischemic insult, a promising finding in the context of perinatal brain injury. This study describes, for the first time mechanistically, the functional characteristics and anatomical integration of nonimmortalized donor SVZ-derived murine aNPCs in the dysmyelinated brain at key developmental time points.