Neurofilament immunoreactivity in developing rat autonomic and sensory ganglia

Immunoreactivity to neurofilament (NF) antiserum appears early in the development of both the central and peripheral nervous systems of the rat fetus. In 10 somite embryos, positive cell bodies are present in the ventromedial part of anterior rhombencephalic and mesencephalic neural tube. From there the appearance of immunoreactivity spreads cranially to the prosencephalic anlage before closure of the anterior neuropore and caudally following the sequence of neural tube closure. Immunoreactivity increases rapidly in axon bundles of central and peripheral systems, but in immature cell bodies of sensory ganglia the NF material only forms a ring around the nucleus. At 16 days of gestation, some cell bodies are progressively loaded with NF-immunoreactive material as a thick perinuclear network first and then in more excentrically located aggregates. This category of neurons is mainly observed in the distal part of the trigeminal ganglion, in petrous and nodose ganglia and in cervical dorsal root ganglia. In adult ganglia large cell bodies and some small ones present high NF immunoreactivity. In autonomic cell bodies (in superior cervical ganglion and in parasympathetic cranial ganglia) the immunoreactive material only forms a perinuclear ring slowly transformed into a loose perinuciear meshwork at the end of gestation. Intensely reactive nerve fibers are observed in cranial sensory as well as in sympathetic and parasympathetic ganglia and nerves. No positive cell bodies and only a few NF-immunoreactive nerves are observed in the carotid bodies. The NF immunoreactivity is better visualized on sections of fresh frozen material, treated with acetone, than in fixed specimens.These results are compared to previous observations reported for other species and for developing dorsal root ganglia. This immunostaining may be used to detect differentiation of peripheral sensory and autonomic neurons under experimental conditions. The uneven distribution of NF immunoreactivity in sensory neurons from stage 16 days of gestation as specific for precise subpopulations of neurons is discussed.     

The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia

Immunohistochemistry for two nociceptive transducers, the vanilloid receptor 1 (VR1) and vanilloid receptor 1-like receptor (VRL-1), was performed on the vagal sensory ganglia. In the jugular ganglion, VR1-immunoreactive (IR) neurons were small to medium-sized (range 49.7–1125.6 μm², mean±S.D. 407.7±219.7 μm²), whereas VRL-1-IR neurons were medium-sized to large (range 223.6–1341.1 μm², mean±S.D. 584.3±253.5 μm²). In the nodose ganglion, VR1- and VRL-1-IR neurons were mostly small to medium-sized (VR1: range 148.5–1464.4 μm², mean±S.D. 554.3±207.4 μm²; VRL-1: range 161.7–1166.2 μm², mean±S.D. 541.9±186.2 μm²). The double immunofluorescence method revealed that co-expression of VR1-immunoreactivity among VRL-1-IR neurons was more abundant in the nodose ganglion (63%) than in the jugular ganglion (4%). The present study suggests that co-expression of VR1 and VRL-1 may be more common in visceral sensory neurons than in somatic sensory neurons.     

The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia

Immunohistochemistry for two nociceptive transducers, the vanilloid receptor 1 (VR1) and vanilloid receptor 1-like receptor (VRL-1), was performed on the vagal sensory ganglia. In the jugular ganglion, VR1-immunoreactive (IR) neurons were small to medium-sized (range 49.7–1125.6 μm², mean±S.D. 407.7±219.7 μm²), whereas VRL-1-IR neurons were medium-sized to large (range 223.6–1341.1 μm², mean±S.D. 584.3±253.5 μm²). In the nodose ganglion, VR1- and VRL-1-IR neurons were mostly small to medium-sized (VR1: range 148.5–1464.4 μm², mean±S.D. 554.3±207.4 μm²; VRL-1: range 161.7–1166.2 μm², mean±S.D. 541.9±186.2 μm²). The double immunofluorescence method revealed that co-expression of VR1-immunoreactivity among VRL-1-IR neurons was more abundant in the nodose ganglion (63%) than in the jugular ganglion (4%). The present study suggests that co-expression of VR1 and VRL-1 may be more common in visceral sensory neurons than in somatic sensory neurons.     

Co-expression of VRL-1 and calbindin D-28k in the rat sensory ganglia

The co-expression of vanilloid receptor 1-like receptor (VRL-1), a newly cloned capsaicin-receptor homologue, with calbindin D-28k was examined in the rat sensory ganglia. The co-expression was rare in the dorsal root, trigeminal and jugular ganglia and abundant in the petrosal and nodose ganglia. In the dorsal root ganglion, none of VRL-1-immunoreactive (ir) neuron co-expressed calbindin D-28k-immunoreactivity (ir). Of the VRL-1-ir neurons, 9 and 5% showed calbindin D-28k ir in the trigeminal and jugular ganglia, respectively. On the other hand, 35 and 63% of VRL-1-ir neurons in the petrosal and nodose ganglia, respectively, co-expressed these substances. The retrograde tracing method indicated that petrosal neurons which co-expressed VRL-1-and calbindin D-28k-ir innervated taste buds in the circumvallate papilla. The present findings may suggest that VRL-1 is associated with chemosensory functions in visceral sensory neurons.     

Delta-opioid receptor-immunoreactive neurons in the rat cranial sensory ganglia

Immunohistochemistry for delta-opioid receptor (DOR) was performed on the rat cranial sensory ganglia. The immunoreactivity was detected in 16%, 19% and 11% of neurons in the trigeminal, jugular and petrosal ganglia, respectively. The nodose ganglion was devoid of such neurons. DOR-immunoreactive (IR) neurons were mostly small to medium-sized (trigeminal, range = 62-851 microm(2), mean +/- SD = 359 +/- 175 microm(2); jugular, range = 120-854 microm(2), mean +/- SD = 409 +/- 196 microm(2); petrosal, range = 167-1146 microm(2), mean +/- SD = 423 +/- 233 microm(2)). Double immunofluorescence method revealed that all DOR-IR neurons were also immunoreactive for calcitonin gene-related peptide. The cutaneous and mucosal epithelia in the oro-facial region, tooth pulp, taste bud and carotid body were innervated by DOR-IR nerve fibers. In the brainstem, IR nerve terminals were located in the superficial medullary dorsal horn and dorsomedial part of the subnucleus oralis as well as the solitary tract nucleus. The present study suggests that DOR-IR neurons may be associated with nociceptive and/or chemoreceptive function in the cranial sensory ganglia.     

Substance P-like immunoreactivity in developing cranial parasympathetic neurons of the rat

Substance P-like immunoreactivity (SPLI) has been observed in cell bodies of fetal cranial parasympathetic ganglia of rat. It first appears at day 16 of gestation at the same time as in cranial sensory ganglia. From day 17 to 21, SPLI neurons constitute most, if not all, submandibular-sublingual and intralingual ganglia, they form 30–40% of otic and pterygopalatine ganglia and numerous such neurons are found in the myenteric plexus of the esophagus as well as in pharyngeal and buccal walls. The immunoreactive material is thinly granular, and its appearance does not change with prenatal development. The immunoreactivity in cell bodies of parasympathetic ganglia decreases at the end of the gestational period, and cannot be evidenced any more in most cells of normal adult ganglia. However, the corresponding SPLI fibers remain intensely immunoreactive. When grafted to rat irides, which have been chemically depleted of intrinsic SPLI fibers, submandibular, otic and pterygopalatine ganglia from pre- or postnatal rats rapidly produce a large amount of SPLI fibers on the iris mimicking the pattern of sensory innervation. This proves the presence of SPLI neurons in adult parasympathetic ganglia, at least in experimental conditions.This study of fetuses and grafts demonstrates the existence of neurons in SPLI parasympathetic cranial ganglia which has been underestimated or ignored previously as a result of observations on adult ganglia. The very large proportion of SPLI neurons in the ganglia of the salivary gland might be of importance for the interpretation of experimental studies on the control of salivation. The presence of SPLI in all three types of peripheral ganglia, sensory, sympathetic and parasympathetic, raises the question of its functional significance in the different compartments of the peripheral nervous system.     

Secretoneurin-like immunoreactivity in rat sympathetic, enteric and sensory ganglia

Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals surrounding many of the postganglionic neurons of the superior cervical, stellate, paravertebral chain ganglia, coeliac/superior mesenteric and inferior mesenteric ganglia. Postganglionic neurons of the superior cervical and other sympathetic ganglia exhibited low-to-moderate levels of SN-LI. In all these sympathetic ganglia, clusters of small diameter (<10 μm) cells, which may correspond to the small intensely fluorescent (SIF) cells, were found to be intensely labeled. Surgical sectioning or ligation of the cervical sympathetic trunk for 7–10 days resulted in a nearly total loss of SN-LI fibers in the superior cervical ganglia, whereas immunoreactivity in the postganglionic neurons and small diameter cells remained essentially unchanged. In the thoracolumbar and sacral segments of the spinal cord, SN-LI nerve fibers were detected in the superficial layers of the dorsal horn as well as in the intermediolateral cell column (IL_p). Occasionally, SN-LI somata were noted in the IL_p. SN-LI nerve fibers formed a delicate plexus underneath the capsule of the adrenal gland, some of which traversed the adrenal cortex and reached the adrenal medulla. While heavily invested with SN-LI nerve terminals, chromaffin cells seemed to express a low level of SN-LI. In the enteric plexus, varicose SN-LI nerve fibers and terminals formed a pericellular network around many myenteric and submucous ganglion cells; the ganglionic neurons were lightly to moderately labeled. A population of ganglion cells in the dorsal root, nodose and trigeminal ganglia exhibited moderate-to-strong SN-LI. The detection of SN-LI in nerve fibers and somata of various sympathetic ganglia, enteric plexus and adrenal medulla and in somata of the sensory ganglia implies an extensive involvement of this peptide in sympathetic, enteric and sensory signal processing.     

Development of substance P-immunoreactive neurons in cranial sensory ganglia of the rat

Substance P-like immunoreactivity has been observed in fetal and adult cranial sensory ganglia. It first appears at day 16 of gestation in sensory neurons of trigeminal, superior-jugular, petrous and nodose ganglia, as well as in the autonomic myenteric plexus, and at day 17 in cervical dorsal root ganglion cells. Substance P immunoreactivity can be visualized much earlier (day 12) in the central nervous system. The ganglionic immunoreactivity subsequently increases during fetal life but drops at birth. The reactive material is first diffuse, then slowly becomes granular, and is mostly concentrated in coarse perinuclear inclusions in adult sensory neurons. Most substance P-positive neurons in trigeminal and superior-jugular ganglia are small, but medium-sized and large positive neurons are also observed in the trigeminal, petrous and nodose ganglia.Our observations give a precise picture of the development of substance P immunoreactivity in sensory neurons and are in general agreement with previous reports on some fetal and adult rat sensory ganglia. They indicate that in the rat, maturation of peripheral substance P-containing sensory neurons is slower than that of central substance P neurons or equivalent sensory neurons in other species. The examination of fetal material allows the observation of numerous immunoreactive sensory neurons which cannot be visualized after birth. We hypothesize a possible different embryonic origin (neural crest or placodal) for small nociceptive and larger substance P-containing neurons in rat cranial sensory ganglia.     

Origin of galanin-immunoreactive nerve fibers in the rat paracervical autonomic ganglia and uterine cervix.

Retrograde axonal tracing with fluorogold in conjunction with immunohistochemistry was used to examine the source of galanin-immunoreactive nerve fibers in the paracervical ganglia and uterine cervix of the female rat. Immunohistochemistry revealed galanin-immunoreactive neuron somata in lumbosacral dorsal root ganglia and around the central canal of the lumbosacral spinal cord (lamina X). Injection of fluorogold into the paracervical ganglia resulted in labelled cells in dorsal root ganglia and the sacral parasympathetic nucleus of the spinal cord; but fluorogold-labelled, galanin-immunoreactive cells were found only in dorsal root ganglia. Injection of the tracer in the cervix resulted in labelled cells in the paracervical ganglia and dorsal root ganglia; however, fluorogold-labelled, galanin-immunoreactive cells were again evident only in dorsal root ganglia. It is suggested that the galanin-immunoreactive nerve fibers and varicosities in the paracervical ganglia and uterine cervix are sensory fibers from spinal dorsal root ganglia. The galanin-immunoreactive varicosities in the ganglia could play a role in the modulation of pelvic visceral activity, while those in the musculature of the cervix could influence contractility.     

trkB-like immunoreactivity in rat dorsal root ganglia following sciatic nerve injury

The expression of full-length trkB protein, the functional high affinity receptor for BDNF and NT-4, was examined by immunohistochemistry in adult rat L4–L5 dorsal root ganglia after different types of sciatic nerve lesions. In normal ganglia, 52.5% of the neurons showed trkB-like immunoreactivity. Size measurements demonstrated that trkB-like immunoreactivity was seen predominantly in small- and medium-sized cells. This was confirmed by the finding that 28% of all trkB-positive neurons showed affinity to RT97, an antibody which lanels a neurofilament epitope specific for medium-sized and large primary afferent neurons. After crush, section or neuroma formation of the sciatic nerve, the proportion of trkB-positive cells was 64.5%, 58% and 61.9%, respectively. Since trkB-receptors are present in regenerating primary afferent neurons, these data could indicate that BDNF and/or NT-4 are involved in sensory nerve fiber regeneration after adult injury.     

Ca2+/calmodulin-dependent protein kinase II in the rat cranial sensory ganglia

Immunohistochemistry for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was performed on the rat cranial sensory ganglia. More than one half of neurons was immunoreactive for the enzyme in the trigeminal (60%), jugular (70%), petrosal (55%) and nodose ganglia (63%). These neurons were mainly small to medium-sized. The co-expression study demonstrated that one half of CaMKII-immunoreactive (ir) neurons was also immunoreactive for calcitonin gene-related peptide (CGRP) or the vanilloid receptor subtype 1 (VR1) in the trigeminal, jugular and petrosal ganglia. In the nodose ganglion, CaMKII-ir neurons were mostly devoid of CGRP-immunoreactivity (ir) (8.2%) whereas the co-expression with VR1-ir was common among such neurons (72%). In the facial skin, nasal mucosa and palate, the epithelium and taste bud were innervated by CaMKII-ir nerve fibers. In addition, the retrograde tracing study demonstrated that 39.6% and 44.8% of trigeminal neurons which were retrogradely traced with fluorogold from the facial skin and nasal mucosa exhibited CaMKII-ir. Forty-six percent of petrosal neurons which innervated the soft palate were immunoreactive for the enzyme.     

The co-expression of P2X3 receptor with VR1 and VRL-1 in the rat trigeminal ganglion

The co-expression of P2X3 receptor with the vanilloid receptor subtype I (VR1) and vanilloid receptor 1-like receptor (VRL-1) was examined in the rat trigeminal ganglion (TG) by a double immunofluorescence method. P2X3 receptor-immunoreactive (ir) neurons were predominantly small to medium-sized (range=93.8-1844.4 microm(2), mean+/-S.D.=503.8+/-286.5 microm(2)); 35% and 9% of P2X3 receptor-ir TG neurons were immunoreactive for VR1 and VRL-1, respectively. Small and medium-sized P2X3 receptor-ir neurons contained VR1-immunoreactivity (ir), whereas medium-sized and large P2X3 receptor-ir neurons showed VRL-1-ir. The retrograde tracing and immunohistochemical methods revealed that 30% of the TG neurons retrogradely labeled from the facial skin and tooth pulp exhibited P2X3 receptor-ir. The co-expression of P2X3 receptor and VR1 was detected in 16% of cutaneous TG neurons and 6% of tooth pulp neurons. On the other hand, the co-expression of P2X3 receptor and VRL-1 was common in tooth pulp neurons (23%) and rare in cutaneous TG neurons (8%). In the tooth pulp, 95% of P2X3 receptor-ir TG neurons contained VRL-1-ir. The present study indicates that P2X3 receptor-ir TG neurons, which co-express VR-ir, are abundant in the facial skin. The tooth pulp is probably innervated by TG neurons, which contain both P2X3-and VRL-1-ir.     

Nicotinic acetylcholine receptors in autonomic ganglia

Although alpha3beta4 subunit combination is clearly prevalent in the nAChRs of autonomic ganglia neurons, the ganglia are strikingly different in the ratio of neurons containing each particular nAChR subunit, as found with immunohistochemical methods and from the analysis of the effects of nAChR subunit-specific antibodies on the ACh-induced membrane currents. In particular, the number of neurons containing alpha3, alpha4, alpha5 or alpha7 subunits is by about three times higher in sympathetic ganglia than in parasympathetic ganglia. This difference may explain why the parasympathetic and sympathetic ganglia markedly differ in their pharmacology. Still, alpha7 subunit makes the highest contribution to ACh-induced membrane current. No correlation between the physiological functions of the ganglia and subunit composition of their nAChRs has been found as yet. High permeability for Ca2+ should permit the nAChRs with alpha7 subunits to influence a variety of Ca2+-dependent events in autonomic neurons. As found with biochemical methods and site-directed mutagenesis, the ACh binding site is formed in the alpha/beta subunits interface by multiple loops containing cysteine, tyrosine and tryptophan amino residues as important for ACh binding. Likewise, both alpha and beta subunits are important for the effects of blocking agents on nAChRs. As found by electrophysiological methods, each neuron of sympathetic and parasympathetic ganglia, as a rule, possesses nAChRs of two groups, "fast" and "slow", with the mean duration of the burst of single channel openings ranging approximately from 5 to 10 and from 25 to 45 ms, respectively. These groups of channels differ from each other with their pharmacology. The burst-like activity of autonomic nAChRs channels is possible only if the disulfide bonds are left intact, otherwise only single openings of the channel are observed. The ionic channel of a nAChRs pentamer is formed by M2 transmembrane segments arranging glutamate, serine, threonine, leucine, and valine rings critical for channel conductance and ionic selectivity. In particular, the mutations V251T and E237A, and insertion of proline or alanine, convert a cation-selective channel into an anion-selective one. The open-channel blockers bind to the nAChR channel at the level where the channel diameter is nearly 12 A, both for "fast" and "slow" channel groups.     

Calcitonin gene-related peptide containing autonomic efferent pathways to the pelvic ganglia of the rat

Indirect immunofluorescence method was employed to investigate the involvement of calcitonin gene-related peptide (CGRP) in the autonomic efferent innervations of the pelvic visceral organs of the rat. Cells labeled with Fast blue (FB) injected into the pelvic ganglia were observed in the sacral parasympathetic nucleus; about 30% of these neurons showed CGRP-like immunoreactivity. These CGRP-like immunoreactive neurons were located in the dorsomedial part of the sacral parasympathetic nucleus, extending their dendrites mediolaterally. FB-labeled cells were also found in the upper lumbar level (L1, L2) of the spinal cord. Some of these neurons also showed CGRP-like immunoreactivity. CGRP-like immunoreactive varicose fibers were seen in the pelvic ganglia surrounding individual ganglion cells. Considerable amount of these fibers were not affected by sensory deafferentation, so they probably originated from autonomic efferent neurons.     

Motor, sensory and autonomic nerve terminals containing NAP-22 immunoreactivity in the rat muscle

Neuron-enriched acidic protein having a molecular mass of 22 kDa, NAP-22, is a Ca(2+)-dependent calmodulin-binding protein and is phosphorylated with protein kinase C (PKC). This protein is localized to the biological membrane via myristoylation and found in the membrane fraction of the brain and in the synaptic vesicle fraction. Recent studies showed that NAP-22 is localized in the membrane raft domain in a cholesterol-dependent manner and suggest a role for NAP-22 in maturation and/or maintenance of nerve terminals by controlling cholesterol-dependent membrane dynamics. The present study revealed the immunohistochemical distribution of NAP-22 in the peripheral nerves in rat muscles. In all examined muscles, nerve terminals in the motor endplates showed NAP-22 immunoreactivity associated with the membranes of synaptic vesicles and nerve terminals. In the muscle spindles, annulospiral endings, which made spirals around the intrafusal muscles, showed intense NAP-22 immunoreactivity. Autonomic nerve fibers around the intramuscular blood vessels also showed the immunoreactivity for NAP-22. NAP-22 immunoreactivity in these peripheral nerves was observed from birth to adulthood (100 days after birth). Though growth-associated protein-43 (GAP-43) immunoreactivity in these nerves was observed from birth, this immunoreactivity decreased from 20 days after birth. These findings suggest that NAP-22 is distributed and regulates functions in the motor, sensory and autonomic nerve terminals in the peripheral nervous system.     

Substance P-like immunoreactivity in human sympathetic ganglia

The substantia nigra (SN) of the cat was shown, by the anterograde and retrograde horseradish peroxidase methods, to contain neurons which send their axons to the caudomedial portions of the suprageniculate nucleus and/or lateroposterior nucleus of the thalamus; these neurons were located in the restricted region in the lateral part of the SN, which corresponds to the pars lateralis of the SN.     

偏头痛与头面部自主神经症状

头面部自主神经症状(CAS)是三叉神经自主神经性头痛(TACs)的典型症状,不是偏头痛的诊断标准,但其在偏头痛患者中并非罕见。伴有CAS的偏头痛(MwCAS)可能是介于偏头痛与丛集性头痛之间的临床亚型,与其他不伴CAS的偏头痛患者(MwoCAS)相比,二者临床特征存在一定的差异,这些差异反映了MwCAS可能发生了更高水平的神经敏化。MwCAS与TACs既有差异又有联系,三叉自主神经反射和下丘脑参与了二者的发病机制。 [国际神经病学神经外科学杂志,2021,48(4): 406-409]     

Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat

The vanilloid receptor-like 1 protein (VRL-1, also called TRPV2) is a member of the TRPV family of proteins and is a homolog of the capsaicin/vanilloid receptor (VR1, or TRPV1). Although VRL-1 does not bind capsaicin, like VR1 it is activated by noxious heat (>52 degrees C). Unlike VR1, however, VRL-1 is primarily expressed by medium- and large-diameter primary afferents, which suggests that nociceptive processing is but one of the functions to which VRL-1 contributes. To provide information on the diverse spinal circuits that are engaged by these VRL-1-expressing primary afferents, we completed a detailed immunocytochemical map of VRL-1 in rat spinal cord, including light and electron microscopic analysis, and generated a more comprehensive neurochemical characterization of VRL-1-expressing primary afferents. Consistent with previous reports, we found that VRL-1 and VR1 are expressed in different dorsal root ganglion (DRG) cell bodies. Almost all VRL-1-expressing cells labeled for N52 (a marker of myelinated afferents), consistent with VRL-1 expression in Adelta and Abeta fibers. EM analysis of the DRG and dorsal roots confirmed this and revealed two categories of neurons based on the intensity of immunolabeling. The densest VRL-1 immunoreactivity in the spinal cord was found in lamina I, inner lamina II, and laminae III/IV. This is consistent with the expression of VRL-1 by myelinated nociceptors that target laminae I and IIi and in nonnociceptive Abeta fibers that target laminae III/IV. Dorsal rhizotomy reduced, but did not eliminate, the immunostaining in all dorsal horn laminae, which indicates that VRL-1 expression derives from both DRG cells and from neurons intrinsic to the brain or spinal cord. Spinal hemisection reduced immunostaining of the ipsilateral dorsal columns in segments rostral to the lesion and in the dorsal column nuclei, presumably from the loss of ascending Abeta afferents, but there was no change caudal to the lesion. Thus, supraspinal sources of dorsal horn VRL-1 immunoreactivity are likely not significant. Although we never observed VRL-1 immunostaining in cell bodies in the superficial dorsal horn, there was extensive labeling of motoneurons and ventral root efferents-in particular, in an extremely densely labeled population at the lumbosacral junction. Finally, many ependymal cells surrounding the central canal were intensely labeled. These results emphasize that VRL-1, in contrast to VR1, is present in a diverse population of neurons and undoubtedly contributes to numerous functions in addition to nociceptive processing.     

Distribution of intravascularly injected lanthanum ions in ganglia of the autonomic nervous system of the rat

Intravascular injection of lanthanum revealed that tight junctions of capillaries in sympathetic ganglia are impermeable to small ions and thus behave like capillaries of the blood-brain barrier. The failure of lanthanum to accumulate in the extracellular space suggests that fenestrated capillaries are not as ion-permeable as use of horseradish peroxidase (HRP) by some authors has indicated. A possible toxic action associated with high concentrations of HRP may be responsible for the high permeability of this substance. Testing with lanthanum demonstrated that sympathetic ganglia possess anatomic features that provide a hematic barrier. The blood-ganglion barrier resembles, but has not yet been demonstrated to be as absolute as the blood-brain barrier.