Abstract Body: Hypertension is one of the main risk factors for cognitive impairment and dementia. We and others demonstrated the role of immunoinflammatory challenges in the establishment of cerebral injury following hypertension, highlighting a major role of inflammatory cytokines as interferon-gamma (IFN-γ) and finding increased parenchymal infiltration of CD8+ T cells.
To establish the mechanistic role of these cells in cognitive impairment we subjected mice lacking CD8 cells (CD8 KO) and matched controls to aortic coarctation (TAC) and performed advanced neuroimaging analyses with a dedicated 7T small animal MRI, evaluating perfusion, brain volumes, and white matter microstructural integrity. Cognitive performance was evaluated at 4 weeks using the Morris Water Maze (MWM) test.
Brain perfusion analyses shown protection from cerebral hypoperfusion in TAC CD8 KO mice compared to TAC WT mice (TAC WT vs TAC KO: 108 vs 148 ml/100g/min, p=0.0298) (Figure A). CD8 KO show preserved microstructural structure at DTI MRI, a typical trait of cerebral injury in clinical and experimental hypertension (Fimbria Fractional Anisotropy, TAC WT vs TAC KO: 0.45 vs 0.54, p=0.0210) , and show no a preserved cognition at MWM (Figure B), with a preserved learning curve at acquisition trial and a preserved memory retention capability evidenced at the probe trial (TAC WT vs TAC KO: 16,4 vs 32.2 seconds spent in platform quadrant, p=0.0014).
The rescue from cerebral injury evidenced at MRI and the absence of cognitive impairment in CD8 KO mice demonstrate the pivotal role of CD8+ lymphocytes in the pathogenesis of hypertension-induced cognitive impairment.