Extracellular Matrix Remodelling in the Human Sural Nerve in Peripheral Vascular Disease

Background and Objectives: Peripheral nerve adaptation to different pathological conditions is accompanied by the remodelling of the nerve's extracellular matrix (ECM). Ischemic conditions caused by peripheral vascular disease are known to affect the function of peripheral nerves; however, the morphological changes to their ECM remain insufficiently examined and understood. Bearing in mind that alterations in collagen I, collagen IV, and laminin content may compromise peri- and endoneurial integrity, the aim of our study was to analyse whether peripheral vascular disease (PVD) induces distinct ECM alterations in the human sural nerve compared with the adaptive remodelling observed in ageing. Materials and Methods: The study aimed to determine the amount of type I and IV collagen and laminin in the perineurium and endoneurium of human peripheral nerves from patients with PVD and to compare the results with those of the age-matched controls. Twenty human sural nerves were harvested from cadavers and amputated limbs-10 from each-and were further distributed into two age groups: below and over 75 years of age. The sural nerve tissue samples were stained immunohistochemically for collagen I, collagen IV, and laminin. We measured the percentage content of these ECM components in the perineurium and endoneurium. For morphometric analysis, we used ImageJ software v1.54d. Results: Perineurial collagen type I and laminin were decreased in the older PVD group, relative to both the younger PVD and the older age group. Within the endoneurium, the expression of collagen type IV was higher in older PVD patients, while both collagen type I and laminin were deposited in lower amounts in the same group compared with the younger PVD group. Conclusions: These findings suggest that age-related ECM remodelling in the peripheral nerve may be impaired under ischemic conditions in older adults, with implications for surgical grafting strategies or neural conduit therapies aimed at promoting functional regeneration.