Morphological and ultrastructural analysis of the watershed zones after stripping of the vasa nervorum.

Peripheral nerve trunks are well-vascularized structures where a well-developed collateral system may compensate for local vascular damage. Vasculitis in nerve has a predilection for epineurial vessels and causes to the peripheral neuropathy, which is a major clinical feature of primary and secondary systemic vasculitides. In the present study, the goal was to simulate the vasculitic neuropathy in rat sciatic nerve and to investigate the watershed zones after stripping of the epineural vessels of the sciatic nerve. Sciatic function index values, light and electron microscopic evaluations of the experimental sciatic nerve suggested that the sciatic nerve was normal except for some watershed zones located in the peripheral part of the nerve. Although there is abundant collateral circulation in the peripheral nerve, distribution of the vessels of the watershed zones as observed in the present study should be elucidated by further studies.

[Morphology of peripheral nerves, their sheaths, and their vascularization]. / Morfología de los nervios periféricos, de sus cubiertas y de su vascularización.

This review aims to update our understanding of peripheral nerves, including the nature and function of their sheaths and, finally, their vascularization. The peripheral nervous system is made up of nerves whose function is to gather stimuli from the periphery as well as to transport the motor, secretory or vegetative responses that are triggered to the periphery. The connective tissue surrounding peripheral nerves all along their extension is made up of endoneurial, perineurial and epineurial. The endoneurium surrounds individual axons, which are grouped in fasciculi, each of which is surrounded by the perineurium and finally, the group of fasciculi that comprise all the axons present in this nerve are surrounded by the epineurium. Axons form an intraneural plexus such that they occupy positions in the various fasciculi along the trajectory of the plexus. The number and size of fasciculi vary along the trajectory of a nerve as a result of the plexus positioning of the axons. Peripheral nerves are richly vascularized throughout their length, with multiple anastomoses forming the intraneural vascular network, which is made up mainly of arterioles, capillaries, postcapillary venules and venules. Regarding the blood-nerve barrier and the existence of capillary permeability: endoneural capillaries have junctions that are stronger than those of the endothelial cells of vessels in the epineurium and perineurium. Two distinct lymph channels networks are present in the peripheral nerve stems and are separated by the perineural barrier. The nervi-nervorum are special nerves of a sympathetic and sensory nature that arise from the nerve itself and the perivascular plexuses.

Increase of mitochondria in vasa nervorum of cases with mitochondrial myopathy, Kearns-Sayre syndrome, progressive external ophthalmoplegia and MELAS.

Previous studies on patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed accumulations of mitochondria in endothelial cells, smooth muscle cells of pial arterioles, and small intracerebral arteries up to 250 microns in diameter; in pericytes of capillaries, endothelial cells, and smooth muscle cells of small blood vessels in skeletal muscle; and according to preliminary results also in endothelial and smooth muscle cells of capillaries and arterioles in sural nerves. These mitochondria do not show the prominent paracrystalline inclusions which are seen in striated muscle fibres and led to the identification of this group of disorders. To corroborate our preliminary findings in peripheral nerves, additional cases have been evaluated morphometrically by electron microscopy including cases in which mitochondrial DNA (mtDNA) mutations have been identified. In fact, an increase of the mean number and an enlargement of the mean cross-sectional area of mitochondria was noted in endothelial and smooth muscle cells of endoneurial and epineurial arterioles, and in endothelial cells and in pericytes of capillaries in sural nerves of the 20 cases with mitochondrial disorders studied. This increase was statistically significant compared to the control group. However, due to heteroplasmia, which is a common feature in mitochondrial disorders, and because of the limited number of measurable blood vessels and cases, no significant differences could be detected between the various types of mitochondrial diseases which were characterized by different point mutations or deletions of mtDNA. Our findings suggest that the mitochondria play a significant role in the pathogenesis not only of myopathic and encephalopathic symptoms, but also in the pathogenesis of peripheral neuropathy which appears to be regularly associated with mitochondrial disorders.

Identification of the characteristic vascular changes in a sural nerve biopsy of a case with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) has recently been identified as a hereditary disorder with characteristic fine structural changes of small intracerebral arteries and arterioles. Electron microscopically there are characteristic perivascular deposits of granular electron-dense material resembling immunoglobulin deposits. The present case from a family with four affected members in three successive generations shows that similar vascular changes as described in the central nervous system are present in blood vessels of the sural nerve, although less pronounced and, therefore, affording electron microscopy for their unequivocal detection. Nevertheless it has been shown for the first time that the diagnosis of CADASIL can be verified by a sural nerve biopsy. Occasional focal accumulation of pinocytotic vesicles opposite the granular deposits suggests exocytosis as one of the possible pathomechanisms for their production.

The vasa nervorum: microcorrosion casts for scanning electron microscopy.

Studies on the vasa nervorum have a long history, not least because of their beneficial application in surgical practice and in understanding the pathogenesis of some neuropathies. In the present study a method is described for the preparation of microcorrosion casts of the vasa nervorum suitable for examination by scanning electron microscopy. The results confirm the findings of earlier investigations but also demonstrate the advantages of an immediate three-dimensional representation of the vascular architecture together with the additional magnification and resolving power of electron microscopy.

Vasculitic neuropathy in panarteritis nodosa: clinical and ultrastructural findings.

Clinical involvement of the peripheral nervous system in panarteritis nodosa is common, but the histological aspects are little known. We describe the sural nerve, muscle and skin biopsy findings in a patient with panarteritis nodosa, affected by mononeuritis multiplex. The data are compared to those reported in other types of vasculitis neuropathy.

The intrinsic vasculature of the lumbosacral spinal nerve roots.

The observations made in this study strongly support the concept that spinal nerve roots in general and the human lumbosacral spinal nerve roots in particular are structurally, vascularly, and metabolically unique regions of the nervous system. Peculiarities of their intrinsic vasculature and supporting connective tissue may account for suspected "neuroischemic" responses to pathologic mechanical stresses and inflammatory conditions associated with degenerative disease of the lower spine. It is hoped that the newly described features of the radicular vasa nervorum (to avoid confusion with the dissimilar blood supply of peripheral nerves, the term "vasa radiculorum" might be more accurate) may advance the understanding of certain aspects of lower spine symptomatology and provide some basis for much needed future research.

Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy.

Onset and nature of ultrastructural changes in endoneurial vasa nervorum during the pathogenesis of leprosy neuropathy and possibly associated alterations in the "blood-nerve barrier" were investigated, together with perineurial barrier functioning, in mice infected 20-28 months previously with Mycobacterium leprae and in (ageing) non-infected mice. Barriers were tested by i.v. administration of markers (Trypan blue and ferritin) 1-4 days before killing the mice. Twenty-eight months after infection, histopathology of sciatic nerves was comparable to that seen in sensory nerves in clinically early human (borderline-) lepromatous leprosy. Schwann cells and endoneurial macrophages were bacillated, endothelia of endoneurial vessels not, and the perineurium rarely. Many infected mice and all (ageing) controls possessed ultrastructurally and functionally normal endoneurial vessels. Their continuous endothelium with close junctions had prevented marker passage, even when surrounding endoneurial tissue cells were quite heavily bacillated. The perineurium was also normal. By contrast, in infected mice showing hind limb paralysis serious histopathologic involvement and large globi of bacilli intrafascicularly in sciatic nerves, endoneurial blood vessels were abnormal. Open endothelial junctions, extreme attenuation, fenestrations, and luminal protrusions were all features comparable to neural microangiopathy encountered in leprosy patients (Boddingius 1977a, b). The "blood-nerve barrier" clearly had become defective allowing excessive exudation of Trypan blue and ferritin, via four pathways from the vessel lumen, deep into surrounding endoneurial tissues but halted by a normal perineurial barrier. Markers in such "blue" nerves were not found in bacillated or non-bacillated Schwann cells, thus denying significant phagocytotic and lysosomal activities of Schwann cells at this stage of neuropathy. Possible implications of barrier performances for anti-leprosy drug treatment of patients are discussed.

Cryoglobulinemic neuropathy: ultrastructural study of the nerve capillaries.

The authors report here the case of a female patient who developed symmetrical polyneuropathy of the lower limbs a few months after she was found to have a myeloma with cryoglobulinemia. In musculocutaneous nerve biopsy material from this patient, electron microscopy showed pathological changes in the nervous tissue together with axonal degeneration and demyelination. But the most striking finding was the presence in the endoneurial space, of numerous masses made up of closely packed tubular structures. These masses occurred also in the walls and even in the lumen of all the vasa nervorum. Their morphologic features and dimensions were identical to cryoprecipitate which the authors extracted from the serum and which they examined with electron microscope.

[Ultrastructure of the blood supplying capillaries of the sciatic nerve in rats]. / Ul'trastruktura krovenosnykh kapilliarov sedalishchnogo nerva krysy.

Electron microscopic studies of the capillaries in the epi-, peri- and endoneurium of the rat sciatic nerve revealed that the capillaries in question possess the features common to the construction of this category of vessels in other organs. In epineurium and perineurium there are capilaries with somatic and visceral types of endothelium. Endoneural capillaries have endothelium of somatic type with ultrastructural features demonstrating its barrier properties. This specificity of endoneural capillaries endotheilum is connected with peculiarities of hemato-neuronal barrier of the peripheral nerves, to which endothelium is an integrated part.