Neuroinflammation and Spinal Cord Pathology Associated with Hypertension in Spontaneously Hypertensive Stroke-Prone Rats

Hypertension is a major contributor to cardiovascular and cerebrovascular disease, leading to significant central nervous system (CNS) damage, including in the spinal cord. This study examines the spinal cord in uncontrolled hypertension of stroke-prone spontaneously hypertensive rats (SHRsp) compared to normotensive Wistar-Kyoto rats (WKY). Histological analyses, including Sudan Black B staining, NADPH-diaphorase histochemistry, immunohistochemistry, and Western blotting, were used to assess inflammation, gliosis, oxidative stress, and axonal injury. SHRsp rats displayed extensive spinal cord pathology, including macrophage infiltration, astrocyte hypertrophy, and demyelination. ED1 immunostaining revealed significant microglial activation in SHTsp, particularly in the ventrolateral white matter, while Sudan Black B staining showed edema and lipid-laden macrophages in dilated perivascular spaces. Increased NADPH-diaphorase activity in SHRsp indicated heightened nitric oxide synthase activity. Glial fibrillary acidic protein (GFAP) immunostaining confirmed significant astrogliosis, with hypertrophic astrocytes more prominent in SHRsp. Western blot analysis showed elevated amyloid precursor protein (APP) levels in SHRsp, associated with axonal injury and oxidative stress. APP-positive phagocytes in white matter further suggested active axonal degeneration. These findings demonstrate significant neuroinflammation, gliosis, and spinal cord tissue damage in hypertensive rats, highlighting the spinal cords vulnerability to hypertension. This underscores the importance of addressing hypertensive damage in the CNS, particularly in patients at risk of neurodegenerative or motor impairments.