Arterial supply of the superior cervical ganglion in the guinea-pig (Cavia porcellus).

The vascularization of the cranial cervical ganglion [superior cervical ganglion (SCG)] of 10 adult guinea-pigs (Cavia porcellus) was investigated by latex injection and dissection techniques. Compared with other species, there were differences in the arterial supply of SCG and in the number of branches originating from these vessels. The SCG received arterial blood from branches of the ascending pharyngeal and internal carotid arteries. In addition, it was demonstrated that the superior thyroid and occipital arteries contribute rarely to the vascularization of the SCG.

Blood supply of the human cervical sympathetic chain and ganglia.

OBJECTIVE: Cadaveric studies of the blood supply to the human cervical sympathetic chain and ganglia are lacking in the English literature. This study seeks to elucidate the gross blood supply of the cervical sympathetic chain so as to avoid surgical disruption of these vessels and thus decrease the risk of vascular insufficieny and subsequent dysfunction of thoracolumbar autonomic outflow to the head and neck. METHODS: Twelve (24 sides) human cadavers (8 male and 4 female) were dissected and their brachiocephalic veins, internal carotid arteries, and vertebral arteries cannulated. Red and blue latex was injected into the arteries and veins respectively. Dissection of the neck was carefully performed and the blood supply of the cervical sympathetic chain identified. RESULTS: The primary arterial supply to the sympathetic chain and ganglia were from superior to inferior the ascending pharyngeal, ascending cervical, thyrocervical trunk, and supreme intercostal arteries. The primary venous drainage of these structures was primarily by direct posterior branches into the internal jugular vein. In addition, we have found an area at the junction of the lower two-thirds and upper one-third of the neck, which is deficient in blood supply (both arterial and venous). CONCLUSIONS: Although sympathetic injury is a rare consequence of cervical operations, the current data should be useful to the surgeon who operates in the cervical region so as to avoid potential complications from disruption of the primary blood supply of the cervical sympathetic chain and ganglia. Also, future techniques of selective iatrogenic disruption of the blood supply to portions of these structures e.g. stellate ganglion may be helpful in treating entities such as hyperhydrosis.

Effect of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes.

AIMS/HYPOTHESIS: Increased oxidative stress has been linked to diabetic neurovascular complications, which are reduced by antioxidants. Our aim was to assess the contribution of hydroxyl radicals to early neuropathic changes by examining the effects of treatment with the specific scavenger, dimethylthiourea, on nerve function and neural tissue blood flow in diabetic rats. METHODS: Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve motor and saphenous nerve sensory conduction velocity. Responses to noxious mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by hydrogen clearance microelectrode polarography. RESULTS: Eight weeks of diabetes reduced motor and sensory conduction velocity by 19.9% and 15.7% respectively, and these were completely corrected by 2 weeks of dimethylthiourea treatment. The ED50 for motor conduction was 9 mg kg(-1) x day(-1). Mechanical and thermal nociceptive sensitivities were 18.9% and 25.0% increased by diabetes, respectively, indicating hyperalgesia which was 70% reduced by dimethylthiourea. Sciatic endoneurial and superior cervical ganglion blood flows were 51.2% and 52.4% reduced by diabetes and there was an approximately 80% improvement with treatment. CONCLUSION/INTERPRETATION: Hydroxyl radicals seem to make a major contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that the development of potent hydroxyl radical scavengers suitable for use in man could markedly enhance the potential therapeutic value of an antioxidant approach to the treatment of diabetic neuropathy and vascular disease.

Diabetes causes an early reduction in autonomic ganglion blood flow in rats.

Impaired blood flow to peripheral nerve trunks makes a major contribution to the neuropathic complications of diabetes mellitus. Comparatively little attention has been paid to perfusion abnormalities for the cell bodies of origin of the autonomic and sensory nerves, although they are severely affected in diabetic neuropathy. The aim was to examine the time course of changes in superior cervical ganglion (SCG) perfusion in streptozotocin-induced diabetic rats. Ganglion blood flow, measured by hydrogen clearance microelectrode polarography, was approximately 70 ml min(-1) 100 g(-1). One week of diabetes caused a 46% perfusion deficit, which was maintained (54%) over 24 weeks. Thus, an early, profound, and long-lived reduction in ganglion perfusion may deleteriously affect neural cell body function and could contribute to autonomic neuropathy.

Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats.

Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha-lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats. alpha-Lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha-Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha-lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by alpha-lipoic acid (ED(50), 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha-lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha-lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach.

Functional and morphologic evidence of the presence of tissue-plasminogen activator in vascular nerves: implications for a neurologic control of vessel wall fibrinolysis and rigidity.

Tissue plasminogen activator (t-PA) is expressed by hypothalamic and peripheral sympathetic neurons. The sympathetic axons that permeate artery walls have not been investigated as possible sources of intramural t-PA. The plasmin produced by such a system would locally activate both fibrinolysis and matrix metalloproteinases that regulate arterial collagen turnover. To assess this neural t-PA production, we investigated the capacity of rat cervical sympathetic ganglion neurons to synthesize and release t-PA, and the expression of the enzyme in carotid artery and the iris-choroid microvascular tissues that receive the ganglion axon distribution. Functional studies confirmed that (i) the ganglion neuron cell bodies synthesize t-PA mRNA, (ii) cultured ganglion carotid artery and iris-choroid microvascular explants predominantly release t-PA rather than urokinase, (iii) microvascular tissues release approximately 20 times more t-PA per milligram than carotid explants (which accords with the higher innervation density of small vessels), and (iv) removal of the endothelium did not cause major reductions in the t-PA release from carotid and microvascular explants. Immunolocalization studies then confirmed a strong expression of the enzyme within the ganglion axons, the carotid adventitia that receives these axons, and the predominantly sympathetic axon terminals in the iris-choroid microvasculature. These data indicate the existence of a previously undescribed system for the delivery of neural t-PA to vessel walls. The intramural production of plasmin induced by this system represents a novel principle for the regulation of arterial matrix flexibility, especially in the media of densely innervated small arteries and resistance arterioles involved in the pathogenesis of stroke, hypertension, and vascular aging. Thus, the data suggest an important new interface between neuroscience and vascular biology that merits further exploration.

Neuropathology and blood flow of nerve, spinal roots and dorsal root ganglia in longstanding diabetic rats.

Vascular perfusion and neuropathologic evaluation of the lumbar spinal roots and dorsal root ganglia (DRG) were studied in rats with longstanding (duration 12-15 months) streptozotocin-induced diabetes and age- and sex-matched control rats. We also undertook nerve conduction studies including F-wave recordings and measured blood flow in sciatic nerve, DRG, and superior cervical ganglion (SCG). Light microscopically, changes of the myelin sheath in the dorsal and ventral roots and vacuolated cells in the DRG were the major findings, being significantly higher in diabetic rats than in control rats. The effects of the diabetic state on myelin splitting were greater in the dorsal than ventral roots. Electron microscopic studies revealed a gradation of changes in myelin from mild separation to severe ballooning of myelin with relative axonal sparing. DRG cells showed vacuoles of all sizes with cristae-like residues, suggestive of mitochondria. These findings suggest that diabetes mellitus has a dual effect: it accelerates the normal age-related degenerative changes in the spinal roots and DRG, and it also has a selective effect on the sensory neuron. Nerve conduction studies showed markedly reduced conduction velocities in the distal nerve segments and prolonged F-wave latency and proximal conduction time despite the shorter conduction pathway in diabetic rats. Blood flow, which was measured using iodo[14C]antipyrine autoradiography, was significantly reduced in the sciatic nerves, DRG, and SCG of diabetic rats. We suggest that the combination of hyperglycemia and ischemia results in oxidative-stress and a predominantly sensory neuropathy.

Investigation of the blood-ganglion barrier properties in rat sympathetic ganglia by using lanthanum ion and horseradish peroxidase as tracers.

Vascular permeability in various rat sympathetic ganglia, including superior cervical ganglia, thoracic ganglia and the celiac-mesenteric ganglia (CMG) complex, was investigated by using lanthanum and horseradish peroxidase (HRP) as tracers with special attention to the neuronal and small granule-containing (SGC) cell area. After lanthanum perfusion, lanthanum tracer was present within the lumen of blood vessels. No lanthanum depositions were found in the extravascular space surrounding neurons in the superior cervical and thoracic ganglia. By contrast, an accumulation of lanthanum was observed in both luminal, abluminal and subendothelial surface of blood vessels in neuronal and SGC cell areas of the CMG complex and surrounding SGC cells in superior cervical ganglia. Injecting HRP revealed that all blood vessels of various sympathetic ganglia, either in neuronal or in SGC cell areas, were impermeable to HRP. HRP reaction product was limited to the vascular lumen and macrophages. The escape of HRP was obstructed by the junctional complex at intercellular clefts of endothelia and also by the diaphragms of the fenestrated capillaries associated with SGC cells. We conclude that there are different properties in the blood-ganglion barriers among rat sympathetic ganglia: (1) continuous capillaries in superior cervical ganglia and thoracic ganglia provide an efficient blood-ganglion barrier that prevents the penetration of tracers, and (2) capillaries in the CMG complex and in regions of the superior cervical ganglia that contain SGC cells possess a selective blood-ganglion barrier that discriminates between tracers based on their molecular sizes.

Cytoarchitecture of the common tree shrew (Tupaia glis) superior cervical ganglion. A scanning electron microscope study on vascular cast/enzyme-digested superior cervical ganglia.

The cytoarchitecture of the superior cervical ganglion of the common tree shrew was investigated by scanning electron microscopy using the vascular cast technique in conjunction with digestion by collagenase-hyaluronidase/HCl. The main cellular constituents were found to be multipolar neurons that were densely distributed throughout the ganglion. These neurons were covered with a smooth cytoplasmic sheath of satellite cells. After the removal of this sheath by digestion of increased duration, the blebs or knobs on the neuronal surfaces became evident. A meshwork of nerve fibers over the surface of neurons was also observed. Preganglionic sympathetic nerve fibers, giving rise to fine branches that ran toward the postganglionic sympathetic neurons before forming synapses, were demonstrated. Groups of neurons surrounded by capillary loops were also frequently observed.