Human dorsal-root-ganglion perfusion measured in-vivo by MRI.

PURPOSE: To develop an in-vivo imaging method for the measurement of dorsal-root-ganglia-(DRG) perfusion, to establish its normal values in patients without known peripheral nerve disorders or radicular pain syndromes and to determine the physiological spatial perfusion pattern within the DRG. METHODS: This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 46 (24 female, 22 male, mean age 46.0±15.2years) subjects without known peripheral neuropathies or pain syndromes were examined by a 3Tesla MRI scanner (Magnetom VERIO or TRIO, Siemens AG, Erlangen, Germany) with a VIBE (Volume-Interpolated-Breathhold-Examination) dynamic-contrast-enhanced (DCE) T1-w-sequence (TR/TE 3.3/1.11ms; 24 slices; voxel resolution 1.3×1.3×3.0mm(3)) covered the pelvis from the upper plate of the 5th lumbar vertebra to the 2nd sacral vertebra. Transfer-constant (K(trans)) and interstitial-volume-fraction (interstitial-leakage-fraction, Ve) were modeled for the DRG and spinal nerve by applying the Tofts-model. Statistical analyses included pairwise comparisons of L5/S1 DRG vs. spinal nerve. Furthermore, distinct physiological zones within the S1 DRG were compared (cell body rich area (CBRA) vs. nerve fiber rich area (NFRA)). RESULTS: DRG showed a significantly increased permeability compared to spinal nerve (K(trans) 3.8±1.5 10(-3)/min vs. 1.6±0.9 10(-3)/min, p-value: <0.001) combined with an increased interstitial leakage of contrast agent into the extravascular-extracellular-space (Ve 38.1±19.2% vs. 17.3±9.9%, p-value: <0.001). Parameters showed no statistically significant difference on DRG-level (L5 vs. S1; p-value: 0.62 (K(trans)); 0.17 (Ve)) and -side (left vs. right; p-value: 0.25 (K(trans)); 0.79 (Ve)). Female gender was associated with a significantly increased permeability (K(trans) female 4.3±1.4 10(-3)/min vs. male 3.4±0.9 10(-3)/min, p-value: <0.05) but no statistically significant differences in interstitial leakage (Ve female 40.1±14,1% vs. male 34.5±17.4%, p-value: 0.24). DRG showed distinct spatial distribution patterns of perfusion: K(trans) and Ve were significantly higher in the CBRA than in the NFRA (K(trans) 4.4±1.8 10(-3)/min vs. 1.7±1.2 10(-3)/min, p-value: <0.001 and Ve 40.9±21.3% vs. 15.1±11.7%, p-value: <0.001). CONCLUSION: Non-invasive and in-vivo measurement of human DRG perfusion by MRI is a feasible technique. DRG show substantially higher permeability and interstitial leakage than spinal nerves. Even distinct physiological perfusion patterns for different microstructural compartments could be observed within the DRG. The technique may become particularly useful for future research on the poorly understood human sensory neuropathies and pain syndromes.

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide.

A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in neuronal systems and exhibits numerous biological activities. Using CGRP-knockout mice (CGRP(-/-)), we examined whether or not endogenous CGRP facilitates angiogenesis indispensable to tumor growth. CGRP increased tube formation by endothelial cells in vitro and enhanced sponge-induced angiogenesis in vivo. Tumor growth and tumor-associated angiogenesis in CGRP(-/-) implanted with Lewis lung carcinoma (LLC) cells were significantly reduced compared with those in wild-type (WT) mice. A CGRP antagonist, CGRP8-37 or denervation of sciatic nerves (L(1-5)) suppressed LLC growth in the sites of denervation compared with vehicle infusion or sham operation. CGRP precursor mRNA levels in the dorsal root ganglion in LLC-bearing WT were increased compared with those in non-LLC-bearing mice. This increase was abolished by denervation. The expression of VEGF in tumor stroma was down-regulated in CGRP(-/-). These results indicate that endogenous CGRP facilitates tumor-associated angiogenesis and tumor growth and suggest that relevant CGRP may be derived from neuronal systems including primary sensory neurons and may become a therapeutic target for cancers.

Role of degenerated neuron density of dorsal root ganglion on anterior spinal artery vasospasm in subarachnoid hemorrhage: experimental study.

BACKGROUND: The spinal arteries are innervated by several systems that contribute to the control of spinal cord blood flow. The sensory fibers of upper cervical nerves have vasodilatatory effect on the anterior spinal arteries (ASA). Subarachnoid hemorrhage (SAH) causes severe vasospasm by various neurochemical mechanisms. We examined whether there is a relationship between the neuron density of the C3 dorsal root ganglion and the severity of ASA vasospasm in SAH. METHODS: This study was conducted on 20 rabbits. Four of them were used as baseline group. Experimental SAH has been applied to all of 16 animals by injecting homologous blood into cisterna magna. After 20 days of injection, ASA and C3 dorsal root ganglia (C3DRG) were examined histopathologically. ASA volume values and normal and degenerated neuron densities of C3DRG were estimated stereologically and the results were analyzed statistically. RESULTS: The mean ASA volume was 1.050±0.450 mm³, [corrected] and the mean neuronal density of C3DRG was 10,500 ± 850 in all animals. The mean volume value of ASA was 0.970±0.150 [corrected] mm³, and the normal neuron density of C3DRG fell to 8,600 ± 400/mm³ in slight vasospasm group. In severe vasospasm-developed animals, mean volume value of ASA was 0.540±0.90 [corrected]mm³ and the normal neuron density of C3DRG fell to 5,500 ± 360/mm³. An inverse relationship between the degenerated neuronal density of the C3DRG and ASA volume values may indicate the severity of ASA vasospasm. CONCLUSION: The neuron density of C3DRG may be an important factor on the regulation of ASA volume values and the continuation of spinal cord blood flow. Low neuron density of C3DRG may be considered as an important factor in the pathogenesis of severe ASA vasospasm in SAH.

Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: implications for chemical-induced peripheral sensory neuropathies.

Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

Neuroprotection of adult human neurons against ischemia by hypothermia and alkalinization.

Ischemia of intact dorsal root ganglia (DRG) in situ leads to massive neuron death due to ischemia-triggered secondary events, such as massive release of excitatory amino acids from the neurons, their excessive accumulation and activation of neuron NMDA and other receptors, acidification, and loss of calcium homeostasis. The present experiments tested whether hypothermia and alkalinization, separately or combined, provide neuroprotection against 1-4 hours of ischemia to the neurons within intact DRG acutely removed from organ donors. DRG under hypothermic (20-15 degrees C) or alkaline (pH 8.0-9.3) conditions yielded more viable neurons than DRG maintained under physiological conditions (37 degrees C/pH 7.4), 4.1-fold vs. 7.8-fold respectively, but, hypothermia and alkalinization combined (20 degrees C/pH 9.3) increased the yield of viable neurons 26-fold compared to DRG maintained under physiological conditions. These results show that combined hypothermia and alkalinization provide adult human DRG neurons significant neuroprotection against ischemia, and ischemia-induced causes of neuron death.

VEGF is required for the maintenance of dorsal root ganglia blood vessels but not neurons during development.

Vascular endothelial growth factor (VEGF) is a potent regulator of vascular function through its control of multiple endothelial cell functions. In addition to its key role in vascularization, VEGF has recently been shown to have neurotrophic activity during hypoxic stress. In the central and peripheral motor nervous system, VEGF treatment increased neuronal vascularization and perfusion, as well as having direct trophic effects on neurons and Schwann cells. However, the role of VEGF in the sensory nervous system remains unclear. To characterize the differential effects of VEGF on endothelial cells and neurons in sensory ganglia, we used explanted mouse dorsal root ganglia (DRG), a culture system containing neurons and endothelial cells in close apposition. We show that VEGF is expressed by neurons and satellite cells, but not by endothelial cells or pericytes. On the other hand, the tyrosine kinase VEGF receptor VEGFR-2 was robustly expressed by endothelial cells throughout the extensive DRG capillary network, but not found at either the transcript or protein level in sensory neurons or other nonendothelial cells of the DRG. Both soluble receptor sequestration of VEGF and small molecule kinase inhibition of VEGFR-2 signaling rapidly disrupted the connectivity, branching, and structural integrity of the capillary network of embryonic DRG; this effect was no longer evident postnatally. However, VEGF inhibition showed no detectable effect on neuronal health at any stage analyzed. These data suggest that endogenous VEGF is a strict requirement for vascular, but not neuronal, maintenance in developing sensory ganglia.

Effect of acute nerve root compression on endoneurial fluid pressure and blood flow in rat dorsal root ganglia.

The objective of the current study was to test the hypothesis that crush injury to nerve root increases endoneurial fluid pressure (EFP) and decreases blood flow in the associated dorsal root ganglion (DRG). A total of 21 adult, female Sprague-Dawley rats had their left L5 nerve root and DRG exposed. The L5 nerve root was clamped for 2 s with a vascular suture clip just proximal to the DRG (compression group). Sham-operated animals without compression were used for control (control group). EFP was recorded with a servo-null micropipette system using a glass micropipette with tip diameter of 4 mum before and after 3 h of treatment. After the final measurement of EFP, DRG was excised and processed for histology. Blood flow in the DRG was continuously monitored by laser Doppler flow meter for 3 h. Three hours after treatment, EFP was 4.7+/-2.7 cm H(2)O in the compression group and 2.2+/-1.2 cm H(2)O in the control group (P<0.05). Edema was the principal pathologic findings seen consistently in the DRG from animals in the compression group. Blood flow in the compression group was reduced 10 min after compression. This reduction was statistically significant compared with that of the control (P<0.01). An acute compression to the nerve root increased endoneurial edema, increased EFP in the associated DRG, and reduced DRG blood flow. This combination of increased EFP and decreased blood flow in the DRG may result in neuronal ischemia and sensory dysfunction. These acute pathophysiologic changes may thus have a role in the pathogenesis of low back pain and sciatica due to disc herniation and spinal canal stenosis.

Patterns of angiogenesis in neural transplant models: I. Autonomic tissue transplants.

Functional vascular connections must form rapidly to prevent ischemic damage to grafted neural tissues. The temporal sequence by which transplant circulation is re-established provides information about the angiogenic capacity of either intact or damaged CNS blood vessels. This study compares the time course and mechanism of vascular reperfusion in allografts of superior cervical ganglia or adrenal medulla inserted either into the fourth ventricle or directly into the parietal cortex of perinatal rats. Tritiated thymidine was administered to recipients to determine angiogenic patterns at various postoperative time periods. After processing for light microscopic autoradiography, host and graft endothelial labelling indices were determined in order to establish the temporal sequence and location of vascular proliferation. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H thymidine prior to transplantation to determine if host vessels invaded the grafts. Intraventricular graft vessels initially collapsed but sustained minimal ischemic damage and were completely reperfused by 24 hours postoperative. Adjacent intact host vessels attained peak 3H thymidine incorporation at 20 hours. Intrinsic graft vessels were radioactively labelled only after 48 hours. Intraparenchymal transplants surrounded by minimal trauma exhibited a similar temporal sequence of reperfusion and host endothelial proliferation. Intrinsic graft vessels in intraparenchymal grafts sustained more severe damage. With increased trauma, a concomitant delay in graft reperfusion time was observed. Grafts within prelabelled hosts rarely contained any labelled endothelium, indicating that anastomotic connections were made between original, intrinsic graft vessels and nearby host vascular sprouts. This study demonstrates that mature autonomic tissue stimulates the growth of adjacent host vessels when transplanted to undamaged brain surfaces. The anastomosis of nascent host vessels with pre-existing graft vessels is responsible for the rapid re-establishment of circulation within the transplants. A similar mechanism occurs within intraparenchymal grafts, although the rapidity of reperfusion appears to be predicated on the amount of trauma present at the graft site.

Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow.

Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia-like behavior to mechanical stimulation which are thought to be mediated by ectopic activity arising in lesioned afferent neurons mainly in the dorsal root ganglion (DRG). It has been suggested that the neuropathic pain behavior is dependent on the sympathetic nervous system. In rats 3-56 days after L5 spinal nerve lesion, we tested responses of axotomized afferent fibers recorded in the dorsal root of the lesioned segment to norepinephrine (NE, 0.5 microg/kg) injected intravenously and to selective electrical stimulation of the lumbar sympathetic trunk (LST). In some experiments we measured blood flow in the DRG by laser Doppler flowmetry. The majority of lesioned afferent fibers with spontaneous activity responded to neither LST stimulation (82.4%) nor NE (71.4%). In those which did react to LST stimulation, responses occurred only at high stimulation frequencies (likely to be above the physiological range), and they could be mimicked by non-adrenergic vasoconstrictor drugs (angiotensin II, vasopressin). Excitatory responses to LST stimulation were closely correlated with the stimulation-induced phasic vasoconstrictions in the DRG. We therefore hypothesized that the activation of lesioned afferents might be brought about indirectly by an impaired blood supply to the DRG. To test this hypothesis we induced a strong and sustained baseline vasoconstriction in the DRG by blocking endothelial nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) applied systemically. L-NAME enhanced baseline vascular resistance in the DRG about threefold and also increased stimulation-induced vasoconstrictions. After L-NAME, the majority of axotomized neurons with spontaneous activity were activated by LST stimulation (76%) or NE (75%). Again, activations closely followed stimulation-induced phasic vasoconstrictions in the DRG provided that a critical level of vasoconstriction was exceeded. In the present study, inhibitory responses to LST stimulation were generally rare and could be reversed to activation by prolonged stimulation or after L-NAME. These results show that sympathetic-sensory coupling occurs only in a minority of axotomized afferents after L5 spinal nerve injury. Like previous studies, they cast doubt on the notion that the L5 spinal nerve lesion is a good model for sympathetically maintained pain. Since responses of lesioned afferent neurons to LST stimulation and NE could be provoked with high reliability after inducing vasoconstriction in the DRG, and since they mirrored stimulation-induced vasoconstrictions in the DRG, it appears that in this model the association of sympathetic activity with afferent discharge occurs mainly when perfusion of the DRG is impaired.

Neurons with access to the general circulation in the central nervous system of the rat: a retrograde tracing study with fluoro-gold.

Central nervous system neurons which have access to the general circulation were identified by injecting the retrograde tracer Fluoro-Gold peripherally. Fluoro-Gold does not penetrate the blood-brain barrier but is taken up by nerve terminals which project to areas supplied by fenestrated capillaries or to the periphery. Fluoro-Gold-accumulating neurons were present in the following regions or cell groups of the central nervous system: diagonal band of Broca; medial preoptic area; organum vasculosum of the lamina terminalis; subfornical organ; anterior periventricular area; paraventricular nucleus; arcuate nucleus; accessory magnocellular nuclei of the hypothalamus; motor neurons of cranial nerves III-VII, and IX-XII in the brainstem and spinal cord; autonomic ganglionic cells of cranial nerve III (Westphal-Edinger nucleus) in the mesencephalon and the intermediolateral column of the spinal cord; sensory ganglia of the cranial nerve V (mesencephalic trigeminal nucleus); and the C1-C2 and A2 adrenergic cell groups in the medulla. In addition, Fluoro-Gold-accumulating neurons were seen in the sensory ganglia of cranial and spinal nerves. Retrograde labeling with Fluoro-Gold can be combined with immunocytochemistry to identify the chemical messengers within Fluoro-Gold-labeled perikarya. Although a large number of neurons are labeled in the central nervous system with Fluoro-Gold when it is administered peripherally, this technique in combination with immunocytochemistry can be a powerful tool to identify selected neuronal systems in the central nervous system.

Unique microvascular characteristics of the dorsal root ganglion in the rat.

Physiological characteristics of dorsal root ganglia microvessels have not been reported in detail. In this study we examined local blood flow and oxygen tension in the L4 dorsal root ganglion (DRG) of the rat. Under normal physiological conditions, local DRG blood flow measured 36.1 +/- 2.7 ml/100 g/min, over twice that within the endoneurium of the sciatic nerve. DRG blood flow was better maintained during hypotension than endoneurial blood flow suggesting partial autoregulation. Unlike endoneurium, there was relative constancy of flow between mean arterial pressures of 60 and 120 mm Hg. Hypercarbia with acidosis, and hypocarbia with alkalosis did not influence blood flow. The histogram of oxygen tensions within the dorsal root ganglion resembled that in brain but included more values at lower tensions than observed in published endoneurial histograms. Theses findings suggest that the DRG differ from endoneurium in ways that reflect the higher metabolic requirements of neural soma.

Neonatal guanethidine treatment alters endoneurial but not dorsal root ganglion perfusion in the rat.

In previous work, we suggested that there were differences in vasoregulation between dorsal root ganglia (DRG) and the endoneurium of peripheral nerve trunks. To investigate sympathetic control of both microvessel beds, we compared local perfusion in the sciatic nerve endoneurium and lumbar DRG of adult Sprague-Dawley rats treated from neonatal day 5 with guanethidine monosulfate to induce adrenergic sympathectomy. Control rats were injected with normal saline. Local blood flow and microvascular resistance were measured using microelectrodes sensitive to the clearance of hydrogen. Guanethidine-sympathectomized rats had higher sciatic endoneurial blood flow and lower endoneurial microvascular resistance than saline-injected controls. In contrast, DRG blood flow was not increased by sympathectomy and was comparable to control values despite the hypotension induced by sympathectomy. The results suggest that sympathetic control of local blood flow and may be less apparent in DRG than endoneurium and that local autoregulation may protect DRG from hypotension.

Responses of axotomized afferents to blockade of nitric oxide synthesis after spinal nerve lesion in the rat.

Lesioned afferents were tested for their responses to blockade of nitric oxide synthesis in the spinal nerve L5 lesion model for neuropathic pain in Wistar rats. Seven single fibers with spontaneous activity split from dorsal root L5 showed no response after non-selective blockade of nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester whereas five were excited after 5-7 min. Three previously silent units were recruited. Blood flow in the dorsal root ganglion decreased. None of fifteen axotomized afferents tested responded to selective blockade of neuronal nitric oxide synthesis with 7-nitroindazole. It is concluded that neuronal nitric oxide is not involved in the generation of spontaneous activity in axotomized afferent neurons in this model. We suggest that the vasoconstriction induced by blockade of endothelial nitric oxide may be responsible for the excitatory responses.

Increased peripheral nerve microvessels in early experimental diabetic neuropathy: quantitative studies of nerve and dorsal root ganglia.

Microangiopathy is an important complication of diabetes mellitus and neovascularity is a feature of human diabetic retinopathy. The objective of this work was to evaluate numbers, areas and size distributions of whole nerve, endoneurial and dorsal root ganglia perfused microvessels in a detailed fashion using unfixed tissues from rats with experimental diabetes. Experimental neuropathy was studied in male Sprague-Dawley rats 12 weeks after streptozotocin or citrate buffer injection. Electrophysiological recordings of sciatic-tibial motor and caudal sensory fibers identified conduction slowing in diabetes indicating neuropathy. Diabetics had a rise in the numbers of whole nerve microvessels and endoneurial microvessels with associated rises in vessel densities and total vessel luminal areas. Increased vessel numbers in 15-30 microm diameter size ranges were particularly prominent. There was a rise in summed vascular areas in diabetics but the mean luminal area of vessels was not increased. Similar, but not significant trends were observed in a selective analysis of endoneurial vessels alone. In contrast, dorsal root ganglia microvessels were not increased in number. Early experimental diabetic neuropathy is associated with increased numbers of microvessels supplying the peripheral nerve trunk, likely representing neovascularity.

Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase.

Horseradish peroxidase (HRP) was found to pass from ganglionic blood vessels into the extracellular space of dorsal root and Vth nerve ganglia within 2 min of intravenous injection in the rat. By 5 min, the tracer had penetrated into perineuronal and periaxonal spaces. A brisk macrophage response occured, and these cells rapidly engulfed the tracer so that it has almost completely disappeared from the extracellular space 2-3 hr. Fenestrated blood vessels, with and without diaphragms were seen within ganglia. On the basis of the pattern of tracer distribution following post-fixation perfusion of HRP, it was concluded that the fenestrations and endothelial intercellular clefts were probably the most important route of tracer leakage. Because of the foreign and possibly toxic nature of the tracer, its movements and fate may not parallel that of normally extravasated proteins.

Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

Nucleus pulposus-induced nerve root injury: relationship between blood flow and motor nerve conduction velocity.

OBJECTIVE: It is well known that nucleus pulposus induces nerve root injury. The aim of this study was to assess the relationship between intraneural blood flow and motor nerve conduction velocity (NCV) after incision of the adjacent disc. METHODS: A total of 65 dogs were used. A left hemilaminotomy was performed, the annulus fibrosus of the L6-L7 intervertebral disc was incised, and nucleus pulposus was gently pushed into the epidural space by saline solution injection. A left hemilaminotomy without disc incision was used as the sham operation. Seven dogs were used for incision and five dogs for sham treatment for each of the following time points: 1 day, 3 days, 1 week, 1 month, and 2 months of exposure. Five additional dogs were used to establish baseline data. Blood flow in the nerve root was measured in the left L7 nerve root with a tissue blood flowmeter, using an electrolytic hydrogen clearance method. Motor NCV over the exposed area of the nerve root was measured using a neurophysiological technique. RESULTS: There was a reduction in blood flow in the nerve root after disc incision that began after 1 day and was maximal after 1 week. This reduction had resolved by 1 month, however. The motor NCV showed a reduction pattern similar to that for blood flow in the nerve root, but reduction did not begin until 3 days after disc incision and was not fully resolved until 2 months. CONCLUSION: This study demonstrates that the reduction and recovery of motor NCV are related to, and preceded by, a reduction in blood flow in the nerve root. The data might provide important information regarding the basic pathophysiological mechanisms of nucleus pulposus-induced nerve root injury.

Bilateral innervation of the cerebral arteries by the superior cervical ganglion in cats.

The effect of removal of the left superior cervical ganglion on the contractile response to norepinephrine (NE) and 5-hydroxytryptamine (5-HT, serotonin) was studied in isolated segments of the middle cerebral artery (MCA) and posterior communicating artery (PCoA) of the cat. Fifteen days after the excision, each dose of NE elicited a potentiated response in both the MCA and the PCoA, whichever side they originated. By contrast, 5-HT induced enhanced vasoconstriction at each dose only in the MCA and PCoA from the left side. When segments of MCA and PCoA from the right side were challenged against 5-HT, a significantly increased response was found only at the first three doses. On the other hand, the NE content of pools made of MCA, PCoA, and anterior cerebral artery from each side was reduced to the same level on both sides after ganglion removal. These results indicate that the excised superior cervical ganglion innervated the MCA and PCoA from both sides of the circle of Willis.

A posterolateral microsurgical approach to extreme-lateral lumbar disc herniation.

Extreme-lateral lumbar disc herniations present a surgical challenge because the conventional posterior approach requires bone resection for complete visualization of the pathology. The authors have identified constant anatomical landmarks in cadaveric dissections that facilitate access to the intervertebral foramen when combined with a posterolateral approach, as described by Watkins, for lumbar spinal fusion. The authors describe a technique that allows rapid localization and safe excision of these extreme-lateral lumbar disc herniations without the need for bone resection.

Application of nucleus pulposus to the nerve root simultaneously reduces blood flow in dorsal root ganglion and corresponding hindpaw in the rat.

STUDY DESIGN: An experimental study to clarify the effects of nucleus pulposus on blood flow in the dorsal root ganglion and hindpaws. OBJECTIVES: To investigate the effects of application of nucleus pulposus to nerve root on blood flow in the dorsal root ganglion and the corresponding hindpaw. SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application of nucleus pulposus into the epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. However, it has not been clarified which of these changes induces symptoms in the lower limbs. METHODS: Sixteen adult, female Sprague-Dawley rats had the left L5 nerve root and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root, just proximal to the dorsal root ganglion (NP group). For control, the same volume of muscle tissue was applied similarly to the neural tissue (control group). Blood flow in the dorsal root ganglion, corresponding hindpaw, and the contralateral hindpaw was continuously monitored by two-channel laser Doppler flowmeter for 3 hours. After measurement of blood flow, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope. RESULTS: Blood flow in the NP group was reduced, not only in the dorsal root ganglion, but also in the corresponding hindpaw. These reductions were statistically significant compared with the control group (P < 0.01). Edema was the principal pathologic finding seen consistently in the nerve roots and in many of the associated dorsal root ganglia from nucleus pulposus-treated animals. CONCLUSION: Application of nucleus pulposus to nerve root decreased blood flow in the dorsal root ganglion and corresponding hindpaw. These basic pathophysiologic changes are associated with compression injuries caused by herniated discs and are accepted neuropathologic mechanisms of injury associated with painful neuropathies. These acute observations in the dorsal root ganglion and the hindpaw may be important initial factors in the pathogenesis of radicular leg pain (sciatica) due to disc herniation.