Research Article| Volume 217, ISSUE 2, P157-163, February 15, 2004

Download started.


Perineurial cell basement membrane thickening and myelinated nerve fibre loss in diabetic and nondiabetic peripheral nerve


      Diabetic neuropathy is associated with changes in the extracellular matrix of the perineurium, including thickening of the basement membrane of the perineurial cells. Peripheral vascular disease (PVD) is a common vascular condition that can occur in the absence or presence of diabetes. Thickening of the vascular basement membrane of the vasa nervorum is associated with both diabetes and nondiabetic peripheral vascular disease. However, perineurial cell basement membrane (PCBM) thickening in the nondiabetic PVD state has not, until now, been investigated. In this study, 36 nerve fascicles were examined from three patient groups: a diabetic group, a nondiabetic PVD group, and a group free of both PVD and diabetes (control group). PCBM thickness, fascicle size, and myelinated nerve fibre (MNF) density were measured in all three groups. Endoneurial blood vessels were also observed for evidence of morphological changes. The results showed that the thickness of the PCBM is significantly greater in the diabetic group in comparison with both the control and the nondiabetic PVD group, and this increase in thickness is linearly related to fascicle size. The thickness of the PCBM was not significantly different between the nondiabetic PVD and control groups. Although both the nondiabetic PVD and diabetic groups showed a loss of myelinated nerve fibres in comparison with the control group, this loss was statistically greater in the diabetic group. The endoneurial blood vessels of both the diabetic and nondiabetic PVD groups showed evidence of endothelial cell hyperplasia, hypertrophy, and basement membrane reduplication.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Johnson P.C.
        • Doll S.C.
        • Cromey D.W.
        Pathogenesis of diabetic neuropathy.
        Ann. Neurol. 1986; 19: 450-457
        • Korthals J.K.
        • Gieron M.A.
        • Dyck P.J.
        Intima of epineurial arterioles is increased in diabetic polyneuropathy.
        Neurology. 1988; 38: 1582-1586
        • Dyck P.J.
        • Lais A.
        • Karnes J.L.
        • O'Brien P.
        • Rizza R.
        Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy.
        Ann. Neurol. 1985; 19: 425-439
        • Dyck P.J.
        • Karnes J.L.
        • O'Brien P.
        • Okazaki H.
        • Lais A.
        • Engelstad J.
        The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischaemia.
        Ann. Neurol. 1985; 19: 440-449
        • Powell H.C.
        • Rosoff J.
        • Myers R.R.
        Microangiopathy in human diabetic neuropathy.
        Acta Neuropathol. 1985; 68: 295-305
        • Malik R.A.
        • Newrick P.G.
        • Sharma A.K.
        • Jennings A.
        • Ah-See A.K.
        • Mayhew T.M.
        • et al.
        Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy.
        Diabetologia. 1989; 32: 92-102
        • Malik R.A.
        • Veves A.
        • Masson E.A.
        • Sharma A.K.
        • Ah-See A.K.
        • Schady W.
        • et al.
        Endoneurial capillary abnormalities in mild human diabetic neuropathy.
        J. Neurol. Neurosurg. Psychiatry. 1992; 55: 557-561
        • Malik R.A.
        • Tesfaye S.
        • Thompson S.D.
        • Veves A.
        • Sharma A.K.
        • Boulton A.J.M.
        • et al.
        Endoneurial localisation of microvascular damage in human diabetic neuropathy.
        Diabetologia. 1993; 36: 454-459
        • Yasuda H.
        • Dyck P.J.
        Abnormalities of endoneurial microvessels and sural nerve pathology in diabetic neuropathy.
        Neurology. 1987; 37: 20-28
        • Gianni C.
        • Dyck P.J.
        Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus.
        Ann. Neurol. 1994; 36: 408-415
        • Bradley J.L.
        • Thomas P.K.
        • King R.M.H.
        • Llewelyn J.G.
        • Muddle J.R.
        • Watkins P.J.
        Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy.
        Diabetologia. 1990; 33: 611-618
        • Johnson P.C.
        • Brendel K.
        • Meezan E.
        Human diabetic perineurial cell basement membrane thickening.
        Lab. Invest. 1981; 44: 265-269
        • Johnson P.C.
        • Doll S.C.
        Dermal nerves in human diabetic subjects.
        Diabetes. 1984; 33: 244-250
        • King R.H.M.
        • Llewelyn J.G.
        • Thomas P.K.
        • Gilbey S.G.
        • Watkins P.J.
        Diabetic neuropathy: abnormalities of Schwann cell and perineurial basal laminae. Implications for diabetic vasculopathy.
        Neuropathol. Appl. Neurobiol. 1989; 15: 339-355
        • Bradley J.L.
        • Thomas P.K.
        • King R.M.H.
        • Watkins P.J.
        A comparison of perineurial and vascular basal laminal changes in diabetic neuropathy.
        Acta Neuropathol. 1994; 88: 426-432
        • Ghani M.
        • Malik R.A.
        • Walker D.
        • Shara A.K.
        • Lowrie C.T.
        • Schall W.D.
        • et al.
        Perineurial abnormalities in the spontaneously diabetic dog.
        Acta Neuropathol. 1999; 97: 98-102
        • Thomas P.K.
        • Berthold C.H.
        • Ochea J.
        Microscopic anatomy of the peripheral nervous system.
        in: Peripheral neuropathy. vol. 1. Saunders, Philadelphia1993: 28-91
        • Tuck R.R.
        • Schmelzer J.D.
        • Low P.A.
        Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy.
        Brain. 1984; 107: 935-950
        • Sunderland S.
        • Bailey K.C.
        The perineurium of peripheral nerves.
        Anat. Rec. 1952; 113: 125-141
        • Corkdiki G.
        • Ruiz-Velasco S.
        • Ortiz A.
        • Vargas G.
        • Teixeira F.
        Limits of fibre distribution in the sural nerve of man.
        Arch. Med. Res. 1997; 28: 183-187
        • Dyck P.J.
        • Gianni C.
        • Lais A.
        Pathologic alterations of peripheral nerves.
        in: Dyck P.J. Thomas P.K. Peripheral neuropathy. Saunders, Philadelphia1993: 514-598
        • Nukada H.
        • van Rij A.M.
        • Packer S.G.K.
        • McMorran P.D.
        Pathology of acute and chronic ischaemic neuropathy in atherosclerotic peripheral vascular disease.
        Brain. 1996; 119: 1449-1460
        • Muona P.
        • Peltonen J.
        • Sirkku J.
        • Uitto J.
        Increased matrix gene expression by glucose in rat neural connective tissue cells in culture.
        Diabetes. 1991; 40: 604-611
        • Ziyadeh F.N.
        Renal tubular basement membrane and collagen type IV in diabetes mellitus.
        Kidney Int. 1993; 43: 114-120
        • Faulk R.J.
        • Scheinman J.L.
        • Maver S.M.
        • Michael A.F.
        Poly antigenic expansion of basement membrane constituents in diabetic nephropathy.
        Diabetes. 1983; 32: 34-39
        • Muona P.
        • Peltonen J.
        Connective tissue metabolism in diabetic peripheral nerves.
        Ann. Med. 1994; 26: 39-43
        • Hill R.E.
        • Williams P.E.
        A quantitative analysis of perineurial cell basement membrane collagen IV, laminin and fibronectin in diabetic and non-diabetic human sural nerve.
        J. Anat. 2002; 201: 185-192