Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice.

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.