Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Intra-operative magnetic resonance imaging in neurosurgery

Intra-operative MRI (iMRI) has been incorporated into modern neurosurgical operating rooms as a guide for neurosurgical interventions for almost ten years. This technology has been shown to be a useful modality in brain tumour surgery and biopsy; its use in spine, vascular and epilepsy surgery has been evolving. It is particularly useful in low-grade gliomas, pituitary adenomas and pediatric tumors

A preliminary sensitivity study of vertebral tethering configurations using a patient-specific finite element model of idiopathic scoliosis

Vertebral Body Tethering (VBT) surgery for skeletally immature idiopathic scoliosis (IS) patients involves anteriorly placed vertebral screws securing a deformable Polyethylene-Terephthalate (PET) tether. Before securing the tether, compressive force is applied between the screw heads along the axis of the spine. There are no clear guidelines regarding the force magnitude required to optimize deformity correction. In the current study, a validated, patient-specific finite element (FE) model of the thoracolumbar spine/ribcage for a 10-year-old IS patient was analysed, to investigate the effect of four different VBT loading scenarios on spinal alignment and biomechanics. The patient-specific FEM was previously validated using clinical results for pre-/post-operative deformity. Linear elastic continuum elements (PET material) were used to tether laterally oriented screws at spinal levels T5–T12, with roughened contact simulating the screws when locked onto the tether. Compressive forces measured intra-operatively during VBT and during anterior scoliosis fusion surgery (FS) were the basis for the four loadcases. The inferior L5 endplate was fixed. After the surgical loadcases, patient-specific, level-wise gravitational loads at all vertebral levels simulated standing. In this preliminary series of VBT analyses, model predictions for corrected Cobb angle/Kyphosis angle/Axial trunk rotation, correction in major curve intervertebral disc wedge angle; and vertebral bone stress, were compared to determine how different surgical tether tension magnitudes affected deformity correction/spinal loading. Results demonstrated varying degrees of improvement in coronal deformity correction could be achieved with different patterns of tethering loads. However, resultant loads on surrounding anatomy must be considered, with associated high spinal tissue loads and increased propensity for asymmetric growth modulation with increasing tether forces.</p