Endoneurial Capillaries Research Articles

Neovascularization after ischemic nerve injury

Because angioneogenesis is associated with wound repair, neovascularization may play an important role in regeneration after nerve injury. This hypothesis was tested in the present study in which the number and distribution of endoneurial capillaries were determined 6 weeks after ischemic nerve injury. The density of capillaries was increased in the central fascicular regions of the distal sciatic and proximal tibial nerves at sites of ischemic injury. This was accompanied by a decrease in intercapillary distance. Neovascularization may be a response to ischemia or a consequence of nerve degeneration or regeneration, the mechanisms of which are poorly understood.

Increased endoneurial albumin in diabetic polyneuropathy.

Albumin was measured in the endoneurium of fascicular biopsies of sural nerves and in plasma from diabetic patients with polyneuropathy by solid phase radioimmunoassay, and normalized to total endoneurial and plasma protein, respectively, to obtain an index of the blood-nerve barrier (BNB-Index). Fifteen diabetic patients with polyneuropathy had a mean BNB-Index of 29.7 +/- 12.6% SD, 3.8 times higher than control values (7.8 +/- 2.0% SD, n = 4). These data suggest that the blood-nerve barrier of endoneurial capillaries is impaired in patients with diabetic polyneuropathy.

On the occurrence of the fenestrated vessels in Wallerian degeneration of the peripheral nerve.

Ultrastructural studies were made on the distal segments of the mouse phrenic nerve after crush injury. In the control, endoneurium contained only unfenestrated capillaries. In the experiment, from day 2 to day 6, endoneurial capillaries occasionally showed fenestrations with the attenuation of its cytoplasm. At this stage, axonal degeneration and myelin breakdown became evident showing early stage of Wallerian degeneration. In addition, detachment of the neighboring endothelial cells concomitant with the invasion of macrophage was also observed. These findings were previously unobserved changes of the endoneurial endothelium in Wallerian degeneration. The significance of the early occurrence of fenestrae was discussed briefly.

A DESCRIPTIVE STUDY OF THE BLOOD VESSELS OF THE SCIATIC NERVE IN THE RAT, MAN AND OTHER MAMMALS

The gross blood supply and internal vascular organization of the sciatic nerve in the rat (and other mammals including man) have been studied by injection, dissection, and microradiographic methods, in thick sections stained for alkaline phosphatase and semithin sections, and by electron microscopy. In the rat, an anastomotic vascular connection from the arteria comitans to the medial femoral circumflex artery is illustrated. In all species studied, the microvascular network of the nerve has an unusually large calibre and wide spacing, particularly when compared with that of skeletal muscle. Arterioles and venules are present within fascicles; the arterioles are thin-walled, with only rudimentary internal elastic laminae. Endoneurial capillaries are large, continuous and nonfenestrated, with prominent (often multiple) basal laminae and an unusually complete pericyte investment. Endothelial junctions appear to vary in type; not all are tight. Pinocytosis is common. The extensively interconnected vascular network of the nerve fascicle may act as an adaptable in situ reservoir for blood in the precise maintenance of the endoneurial milieu.

Experimental cold injury to peripheral nerve.

Focal non-freezing injury to rat sciatic nerve resulted in nerve conduction block and cessation of axoplasmic transport. Rats showed early functional recovery but subsequently developed a slowly progressive sciatic nerve paralysis. Horseradish peroxidase studies revealed prominent nerve oedema with early enhanced pinocytosis and later, passive leakage through damaged endoneurial capillaries. Detailed microscopy indicated a striking selective vulnerability to cold based on nerve fibre diameter. Unmyelinated fibres were spared while large myelinated nerve fibres showed severe axonal degeneration. Paranodal and segmental demyelination were infrequent findings and may have resulted from early axonal swelling. Possible pathogenic mechanisms to explain the degeneration of myelinated fibres in hypothermic injury are discussed. It is concluded that the gradient of clinical severity seen in limb hypothermic injuries has a pathological correlate in peripheral nerve.

Blood nerve barrier in rat and cellular mechanisms of lead-induced segmental demyelination.

Feeding of lead carbonate to rats causes widespread and reproducible segmental de- and remyelination of myelinated fibers (MFs) of peripheral nerve. Such segmental demyelination might be explained by increased permeability of endoneurial capillaries to serum containing protein-bound lead. The perineurium of control and lead nerves was impermeable to fluorescein-labeled bovine albumin (FBA) and to horseradish peroxidase (HRP). Epineurial capillaries in both conditions allowed HRP to pass freely between and, to a lesser extent, through endothelial cells. Confirming earlier work, endoneurial capillaries of control rats did not appear to allow HRP to pass between endothelial cells, but allowed some to pass by pinocytosis through endothelial cells where it was taken up by macrophages. Contrary to expectation, flooding of the endoneurium with HRP was seen in only 1 of 36 tissue blocks of lead nerves from rats fed 4% lead carbonate for 7 1/2 and 12 weeks. Abundant HRP reaction product was seen in the epineurium in more than half of these tissue blocks. HRP was not generally found in endoneurial fluid, even in lead nerves with marked edema and widespread segmental de- and remyelination. These findings are against a massive breakdown of the blood nerve barrier, so that HRP passes freely into the endoneurium between endoneurial endothelial cells. It was our impression that HRP reaction product was slightly increased in endoneurial endothelial cells and macrophages of lead nerves as compared to control nerves. These studies suggest that there may be an increased transfer of HRP through endoneurial cells in lead neuropathy. The studies do not provide additional evidence that an altered blood nerve barrier is involved in the development of segmental demyelination in lead neuropathy.

Morphometric Comparison of Capillaries in Muscle Spindles, Nerve, and Muscle

Morphometric study was performed on transverse sections of microdissected muscle spindles from rabbit tenuissimus muscles. It showed a statistically significant difference in size and structure between the intrafusal capillaries and those of extrafusal muscle. The former are larger in diameter, circumference, and area due to a proportionate increase in the number of endothelial cells. Vesicles within spindle endothelial cells are fewer, mitochondrial counts are greater, but in proportion to the increased number of endothelial cells, intercellular junctions are tight and pericyte coverage is greater. The basement membrane around endothelial cells and pericytes is thicker and more often multilayered. The endoneurial capillaries of tenuissimus intramuscular nerve are morphologically identical to intrafusal capillaries. The similarity of the capillaries of spindles to those in brain suggests that a blood-nervous system barrier extends from brain into the peripheral nerves and muscle spindles.

Permeability of muscle spindle capillaries and capsule

The permeability of capillaries in rabbit muscle spindles, intramuscular nerves, and extrafusal muscle to intraaortically infused horseradish peroxidase (HRP) was studied. The permeability of the capsule cells of the muscle spindles was also examined. Immediately following the infusion of HRP, most extrafusal capillaries contained a dense accumulation of HRP reaction product, which began to escape into the surrounding extracellular space within 2-3 min. In contrast, the concentration of HRP in the intrafusal and endoneurial capillaries was much lower than that in extrafusal capillaries, and HRP was never found outside the former vessels. In addition, HRP never completely penetrated through the spindle capsule from the extracellular into the periaxial space, although it was regularly found between the outer two or three layers of capsule cells. The results indicate that the permeability characteristics of the muscle spindle capillaries and capsule to the tracer protein HRP are very similar to those of capillaries in peripheral nerve.

Licht- und elektronenmikroskopische sowie cytometrische Untersuchungen an peripheren Nerven beim Morbus Tangier

A sural nerve biopsy was performed in a 55-year-old male patient with Tangier disease (familiallipoprotein deficiency). Light-microscopy showed an increase in the endoneural connective tissue and a loss of nerve fibers indicating a chronic peripheral neuropathy. Electron-microscopy revealed an accumulation of lipid droplets within Schwann cells of myelinated and unmyelinated nerve fibers. When compared with age-matched controls the myelinated fiber density was reduced with a relative preponderance of small myelinated fibers. In addition, distributional cytometric studies of nerve vibers in relation to the perineurium and endoneurial capillaries showed: Contrary to 4.6–7.5 μm thick nerve fibers, which accumulated in the center of the nerve fascicle, small (0.5–4.5 μm) and large (7.6–10.0 μm) fibers lay nearby the perineurium. The measured increase in small myelinated nerve fibers around endoneurial capillaries may be explained as a sign of regeneration.

Ultrastructural study of pheripheral nerve in 16 diabetics without neuropathy. Comparisons with 16 diabetic neuropathies and 16 non-diabetic neuropathies (author's transl)

The present communication described changes on nerve biopsies from 16 diabetics without neuropathy, except the fact that the ankle jerks were often decreased bilaterally, as it is often encountered in diabetes mellitus. 16 non-diabetic patients with various peripheral neuropathies were also studied; the glucose tolerance tests were always normal in this group and none had any vascular or collagen disease. The three series included patients between 45 to 75 years old. Obervations made on nerve biopsies from these three groups have been compared. The basement membranes of endoneurial capillaries were measured. These measurements have been made on the thinnest part of the basement membranes and pericyte processes were not included. At least 5 capillaries per 1 patient have been studied. Averaging with a computer has permitted demonstration of significant thickenings of basement membranes in diabetic patients without neuropathy; such an observation was not made in non-diabetic patients with various peripheral neuropathies, while the thickenings were the most important in patients with diabetic neuropathy. It must be said that individual variations were encountered in each group. Nerve parenchyma has been carefully studied. In diabetic patients without neuropathy, 14 cases displayed a typical but usually moderate proliferation of Schwann cells. Axon lesions were mild and unfrequent. The exact relationships between thickening of basement membranes of vasa nervorum and lesions of nerve parenchyma need some further informations.

Les neuropathies periphériques du diabète sucré: Étude ultrastructurale de 12-cas biopsies

Twelve diabetic patients with peripheral neuropathy underwent sural nerve biopsy. Transverse thick sections of the nerves, fixed in glutaraldehyde, embedded in epoxy and stained with toluidine blue were viewed under the light microscope and ultrathin sections were examined with the electron microscope. In 1 case, the nerve damage was not very severe but in 7 other cases there was evidence of segmental demyelination in addition to axonal degeneration in the same nerve; in 4 cases the lesions were severe. In 11 cases, some onion bulb formations were occasionally seen; they were numerous and large in 5 of them. The endoneurial capillaries were carefully studied and measured. All those seen showed thickening of basement membranes which were multilayered and between the layers one could see some thin collagen fibrils. Such lesions were characteristic of the so-called “diabetic microangiopathy”. These alterations were moderate in 2 cases, more severe in 7 others and very severe in 3 cases which were 3 of the 4 which showed severe lesions of the nerves. It is possible that the presence of these diffuse changes in the endoneurial capillaries could affect the local exchange of metabolites and so produce nerve damage.

A study of hematic barriers in peripheral nerves of albino rabbits.

AbstractHematic barriers were studied in femoral and sciatic nerves and their peripheral branches in male albino rabbits by means of fluorescence microscopy and ultra‐freezing and drying technics. The fluorescent tracer used was a diaminoacridine, acriflavine neutral, which is non‐toxic at the 20 mg/kg dose administered intravenously, has a low molecular weight (259.7), and has a unique quality of chemically binding in vivo with nuclear DNA and RNA. This latter property of acriflavine neutral permitted the observation of fluorescent nuclei where the substance penetrated and no fluorescence where it did not penetrate. The interface between the two regions was identified as a locus of a hematic barrier.Three hematic barrier loci were observed in spinal nerves and their branches: (1) in the plasma membranes of the cells forming inner lamellae of the “perineurial epithelium,” (2) in the luminal face of the plasma membrane of endothelialcellsforming the wall of endoneurial capillaries, and (3) in the “perineurial epithelial” sheath which surrounds endoneurial precapillaries. These barriers appeared to be dependent on normal living physiologic processes for their proper maintenance. In addition, they were very similar to some of the hematic barriers associated with the central nervous system.

Permeability of blood nerve barriers in the diabetic rat.

An albumin-Evans blue conjugate has been used as a fluorescent tracer to demonstrate the increased permeability of endoneurial capillaries and perineurial sheath of the sciatic nerve of the alloxan-diabetic rat. The significance of the extravasation of protein into the endoneurial space is discussed in relation to the altered dynamics of the endoneurial microcirculation. It is suggested that tissue hypoxia produced in this way may be a cause of the segmental demyelination which occurs in these nerves.

Stability of the potassium content of cerebrospinal fluid and brain.

Stability of the potassium content of cerebrospinal fluid and brain.