Rom J Leg Med [22] 69-80 [2014]
DOI: 10.4323/rjlm.2014.69
© 2014 Romanian Society of Legal Medicine Perenity of phenotype changes undergone by neuronal structures inside
human superior cervical sympathetic ganglion. Implications in pathology
Gheorghe S. Drăgoi1,*, Petru Razvan Melinte2, Dragos Marinescu3, Ileana Dincă2, Mihaela Mesina Botoran2
_________________________________________________________________________________________
Abstract: The authors proposed themselves to review the problems regarding the structural stability of neuronal
sympathetic ganglia in humans. The use of reduced silver nitrate Nonidez’s block method allowed the visualization and evaluation
of the following processes inside adult superior cervical sympathetic ganglion: neurons phenotype changes, heterogeneous space
distribution of axons, dendrites and lipofuscine granulations, neuronal apoptosis and variable neurovascular relations. The
authors consider that considering the apoptosis process, the perenity of phenotype changes undergone by neuronal structures
is determined in adult individuals by the presence of stem-like cells migrated from neural crest to dendrites glomerular
compartments. Psychopathologic conditions are equally discussed.
Key Words: human superior cervical sympathetic ganglion, apoptosis, axonal and dendrites glomeruli, regenesis, stemlike cells.
T
he heterogeneity of microanatomic structures
inside autonomous sympathetic neuronal
system has drawn the attention of many researchers
due to the perenity of phenotype changes undergone by
its structures. In the evaluation of phenotype changes
involving the structures of sympathetic ganglia, many
questions were imposed by many complex microanatomic
studies and researches: What is the anatomic criterion for
classifying neurons? What are the phenotype characteristics
of dendrites, axon and perikaryon? What is the trajectory
of axon and dendrites regarding perikaryon? What is the
significance of location existence of neuron groups inside
nervous fibers networks from the structure of “interneuron
glomeruli”? How and why is the nervous fibers network
achieved at the pepikaryon periphery? Why is it necessary
the existence of a capsule around perikaryon? Why are there
intracapsular dendrites? What are the determining factors
of time and space progression of neuronal apoptosis? Is
there a relation between the topography of axons and the
apoptosis process? What is the pathologic and gerontology
signification of the apparition, topography and disappearance
of lipofuscine granules inside perikaryon neuroplasma?
Is there a correlation between apoptosis and lipofuscine
granules? What is the location and evolution capabilities
of autonomous stem cells migrated from neural crest?
The purpose of the study is to review, by means of
classic microanatomic methods, the problem of phenotype
changes involving the neuronal structures inside superior
cervical sympathetic ganglion. The objectives of the paper
were determined by the use of reduced silver nitrate Nonidez’s
block method that allows the visualization and evaluation
of neuronal structures (perikaryon, dendrites, axons), of
the structures achieved by dendrites and axons (dendrites
glomeruli inside and outside neuronal capsule; axons nests
around perikaryons) and of apoptosis in correlation to the
presence of lipofuscine granules and stem-like cells.
1) Romanian Academy of Medical Sciences, Bucharest, Romania
* Corresponding author: Prof.MD,PhD, E-mail [email protected]
2) University of Medicine and Pharmacy of Craiova, Department of Anatomy, Craiova, Romania
3) University of Medicine and Pharmacy of Craiova, Department of Psychiatry, Craiova, Romania
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Drăgoi G.S. et al Perenity of phenotype changes undergone by neuronal structures inside human superior cervical sympathetic ganglion
MATERIAL AND METODS
The study was carried out on six superior cervical
sympathetic ganglions, harvested bilateral from three adult
male cadavers (58-64 years old), respecting the deontological
code of medical and scientific research. While dissecting
the anterior and lateral regions of neck, we visualized the
ganglion at the level of transverse processes of the 2nd and 3rd
cervical vertebras, in close relation to lamina prevertebralis
of fascia colli, in retrostilian space, posterior from internal
carotid artery. The harvest was performed after the isolation
of glossopharyngeal nerve (anterior), inferior ganglion
of vagus nerve (anterior and lateral), hypoglossal nerve
(posterior and superior) and superior laryngeal nerve
(anterior).
Microanatomic preparation was achieved after
reduced silver nitrat - Nonidez’s block method [1, 2]. The
harvested ganglion was fixed in chloral hydrate (25 mg) –
ethanol 50% solution (100 ml). This fixation ensures a good
impregnation in 2% water solution of silver nitrate after a
previous treatment with diluted solution of ammonium
hydroxide (0,5 ml) in ethanol 95% (100 ml). After
impregnation, the ganglion was introduced in the reducing
mixture of pyrogalol (3 mg), formaldehyde 40% (8 ml) and
distilled water (100 ml). Paraffin embedding was performed
after dehydration in alcohols with variable concentrations
and after clarification in xylene. The 5 microns thick serried
sections were mounted in synthetic resin. The microanatomic
examination was carried out using a Nikon microscope. The
imagery was shot with a Nikon Digital Sight DS-Fi1 HighDefinition Color Camera Head and processed by Adobe
Photoshop CS 5.1 software.
RESULTS
The evaluation of phenotype changes involving
the structures of superior cervical sympathetic ganglion is
possible after a microanatomic analysis of: the topography
of neuronal, vascular and connective tissue structures; the
space distribution and phenotype of neurons; the markers
for phenotype changes and last but not least the structure of
regeneration glomeruli.
A. Microanatomic analysis of the topography of
neuronal, vascular and connective tissue structures
When examining the serried sections with the 10x
objective one can easily notice the architectural heterogeneity
of superior cervical sympathetic ganglion (Fig.1 A). At the
periphery of the serried sections we identified a topographic
sector that contains fascicles of neurofibers that alternate
with connective tissue and vascular spaces containing islands
of perikaryons. Centripetal visualization of microscopic
fields allows the identification of neurofibers flanked by
conjunctive and vascular bands of variable thickness. In
some isolated areas we observed islands of perikaryons
arranged in chains (Fig. 1 A, F). Small arteries were noted
inside interfascicular conjunctive spaces (Fig. 1 A, C).
Analyzing the anatomic fields with 20x and 40x objectives
70
permitted the identification of neurofibers networks that
incorporated perikaryons (Fig. 1 B, C). Equally, one can
notice the presence of numerous perikaryons in apoptosis,
even in close proximity to permeable blood vessels (Fig. 1 C).
B. Microanatomic analysis of the variable
neurovascular relations
Microanatomic visualization with 20x, 40x and 60x
objectives of numerous permeable blood vessels reveals the
relations between neurofibers fascicles and blood vessels
walls (Fig. 2A). We noticed a great variability regarding these
relations. Some fascicles of neurofibers are tangent to the
external tunic of small arteries (Fig. 2 B), some circumscribe
the blood vessel wall (Fig. 2 B, E, F, H, I), a great part have
oblique trajectory to the longitudinal axis of blood vessels
(Fig. 2 A, C, D) and some are parallel to themselves and to
the conjunctive tissue that surrounds the vascular groups
(Fig. 2 E, G, H). In the close neighborhood of blood vessels
there is connective tissue with numerous perikaryons, some
of them in apoptosis (Fig. 2 A-H).
C. Microanatomic analysis of perikaryon space
distribution
When examining the serried sections with 20x and
40x objective there is a characteristic space distribution of
perikaryons. Groups with variable number of perikaryons
are distributed in space suggesting a bunch of grapes (Fig. 3).
The central axis of this construction is formed by a fascicle
of neurofibers with lateral ramifications (Fig. 3 A-H). The
number of perikaryons adherent to this axis varies between
two and six and they have an almost symmetrical location.
There is a great variability in the way the central axis branches.
Apoptosis is obvious on numerous anatomic fields. “Ghosts”
of perikaryons in apoptosis appear surrounded by axon
endings (Fig. 3 I).
D. Analysis of microanatomic criteria necessary
for neuron phenotyping
For microanatomic phenotype establishment of
neurons we took into consideration many morphologic
criteria: the topography and histologic genesis of neurons;
lengh and thickness of dendrites; location and relations of
axons; form and relations of perikaryons; space distribution
of short dendrites and their relations to satellite cells from
the structure of the capsule surrounding perikaryon; the
presence and dispersion of lipofuscine granules inside
neuroplasma; neurons involvement in the formation of
networks and/or dendrites glomerular structures. Short
dendrites were visualized both underneath (Fig. 4 A-C)
and outside the capsule (Fig. 4 D-F). When examining with
60x and 100x objectives we stated the radial, centrifuge
distribution of short subcapsular dendrites. They have
relations to satellite capsular cells that they circumscribe
(Fig. 4 A-C) and some have buttoned endings (Fig. 4 B).
Between perikaryon and the capsule that surrounds it we
identified a space crossed by short subcapsular dendrites.
Their radial distribution forms simple glomerular structures
located underneath the capsule and known as dendritic
Romanian Journal of Legal Medicine crown (Fig. 4 A-C, G). In some areas we identified thin short
dendrites that reach the capsule and present fine and low
impregnated endings (Fig. 4 A, B). When examining with
the 60x objective we observed thick dendrites that together
with axonal endings form simple extracapsular glomeruli
in the close proximity of neuronal capsule (Fig. 4 G).
Extracapsular dendrites are long and thick (Fig. 4
D-F) and they participate in the formation of extracapsular
composed glomeruli (Fig. 4 H-N). From their subcapsular
origin, dendrites branch and achieve dendritic networks
and/or composed glomeruli. Numerous dendrites have
terminal buttons (Fig. 4 G-I). When examining with
40x objective one can see the formation of extracapsular
composed glomeruli made of a variable number of neurons;
thus, we talk about bineuronal (Fig. 4 J, K), trineuronal (Fig.
4 M) and multineuronal (Fig. 4 L, N) glomeruli. Bineuronal
glomeruli have two neurons separated by a variable space.
Trineuronal glomeruli are larger, have neurons arranged in
a curve trajectory and their dendrites give secondary and
tertiary branches with terminal buttons (Fig. 4 M). There are
only few multineuronal glomeruli; they are formed of more
than three neurons and can achieve plexiform dendritic
networks; the neurons are either separated or united by
neurofibers of variable thickness.
E. Microanatomic analysis of markers for
phenotype changes involving neuronal structures
Phenotype changes of neuronal structures
are determined by three fundamental processes: the
accumulation of lipofuscine granules inside perikaryon
neuroplasma; neuronal apoptosis and the variability of
dendritic and/or axonal endings (Fig. 5). Space distribution
of lipofuscine granules is variable. They can appear as
isolated gatherings around nucleus (Fig. 5 A); as a crown
around nucleus (Fig. 5 B); crescent like distribution inside
neuroplasma (Fig. 5 D); all over neuroplasma creating an
ovoid (Fig. 5 C); near the membrane of perikaryon (Fig. 5
E); chaotic disseminated inside apoptotic neurons (Fig. 5 F).
Neuron apoptosis is present even near perfectly permeable
blood vessels (Fig. 2 A-I). In some places, one can notice
the decrease until disappearance of lipofuscine granule
in apoptotic neurons (Fig. 5 G-K). The examination with
60x and 100x of microanatomic serried sections allowed
the visualization of dendrites and axons, the identification
of dendritic and axonal endings and of their relations to
apoptotic perikaryon (Fig. 5 H-O). Dendrites and their
branches have circumferential and tangent trajectory
regarding the capsule surrounding perikaryons (Fig. 5
G, H). Pericapsular axonal endings were identified on
equatorial, pole (superior, inferior), southern secant and
tangent sections to capsular spheroid around perikaryons
(Fig. 5 I-M). These endings are applied to the perikaryon
capsule forming a capsular branching resembling a “birds’
nest” (Fig. 5 L-O).
F. Analysis of location and relations of
sympathoblast-like cells in the structure of “regeneration
glomeruli”
Vol. XXII, No 1(2014)
The constant coexistence in time and space of
neuronal and glomerular structures, and apoptotic neurons
raises many problems regarding the presence of cells
capable of regeneration inside superior cervical sympathetic
ganglion. This hypothesis is sustained by the presence during
histologic genesis of stem-like cells migrated from neural
crest. On the serried sections through 6 weeks old embryo we
identified the presence, location and relations of neural crest
(Fig. 6 A). When examining with 60x objective the embryo
neural crest, we easily noticed the presence of stem-like
cells with hyper chromatic nucleus, creating aggregates in a
rosette shape (Fig. 6 B). At the level of dendritic glomerulus
inside superior cervical sympathetic ganglion, we noted the
existence of compartments limited by the dendritic branches
of adjacent neurons (Fig. 6 C, E). In these spaces, when we
examined with 40x and 60 x objectives, we visualized cells
with extremely delicate argirofile expansions that we named
stem-like cells (Fig. 6 E, F).
DISCUSSIONS
Microanatomic analysis using the argentic
impregnation method for the study of neuronal, conjunctive
and vascular structures inside human superior cervical
sympathetic ganglion allowed the evaluation of topography
and phenotype changes undergone by perikaryons
and neurofibers fascicles as well as the knowledge of
variable neurovascular relations, axonal and dendritic
glomerular structures architecture and last but not least,
the identification of markers for phenotype transformation
involving neuronal structures.
A. Considerations upon the progress in the history
of knowledge regarding sympathetic neuronal system
In the history of knowledge regarding sympathetic
neuronal system, there were several hypotheses about
the origin of neuronal system structures, its functional
autonomy and equally about the microanatomy of its
structural elements during ontogenesis dynamics.
1. Problems of origin and terminology
In the empiric stage of knowledge of neuronal
system, there were the hypotheses regarding the origin of
sympathetic neuronal system. Although the existence of
two ganglion chains on both sides of vertebral column was
noticed and accepted by anatomists such as Hippocrat [3],
Galen [4] and Vesale [5] still there were divergent opinions
about their belonging to peripheral neuronal system.
Hippocrate’s school, it was considered that the cervical
sympathetic system was a corresponding to the vagus
nerve. Galen (1597) [4] and Vesale (1543) [5] described it
like a cranial nerve branched off trigeminal or vagus nerve.
Rioland (1608) [6] who adds its medullary origin and names
it “intercostal nerve”.
2. Progresses achieved in multidisciplinary research
on sympathetic ganglion system
During the anatomic and functional stage, Willis
(1664) [7] launched the concept of autonomy of sympathetic
neuronal system and its involvement in vegetative reflexes.
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Drăgoi G.S. et al Perenity of phenotype changes undergone by neuronal structures inside human superior cervical sympathetic ganglion
Figure 1. Microanatomic topography of neuron, connective tissue and vascular structures inside superior cervical sympathetic
ganglion. 1. Neurofibers fascicle flanked by vascular and connective tissue bands; 2. Island of perikaryons inside vascular and
connective tissue; 3. Vascular and connective tissue compartment between fascicles; 4. Topographic sector that contains neurofiber
fascicles, vascular and connective tissue spaces and islands of perikaryons; 5. Perikaryons in a neurofiber network; 6. Small arteries
inside a vascular and connective tissue space; 7. Bineuron glomerulus; 8. Perikaryon with long and short dendrites; 9. Neurons
in apoptosis; 10. Chain of perikaryons limited by neurofiber fascicles.Parafin section. Reduced silver nitrate Nonidez`s block
method Microphotos by Nikon Digital Sight DS-Fi1 High-Definition Color Camera Head. x70 (A); x140 (B;C) ; x280 (D-F).
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Figure 2. Variable relations between neuronal and vascular structures inside superior cervical sympathetic ganglion. 1. Fascicles
of neurofibers inside the connective tissue around blood vessels; 2. Blood vessels sectioned under variable angles; 3. Neurons
located at the periphery of vascular and connective tissue spaces; 4. Fascicles of neurofibers tangent to the external tunic of blood
vessels; 5. Fascicles of neurofibers with oblique trajectory regarding the longitudinal axis of blood vessels.Parafin section. Reduced
silver nitrate Nonidez`s block method. Microphotos by Nikon Digital Sight DS-Fi1 Hight-Definition Color Camera Head. x140
(A-D); x280 (E-H); x420 (I).
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Drăgoi G.S. et al Perenity of phenotype changes undergone by neuronal structures inside human superior cervical sympathetic ganglion
Figure 3. Perikaryons space distribution around a central axis represented by a fascicle of neurofibers with lateral branching (1).
This architecture resembles “a bunch of grapes”(2).The number of perikaryons attached to this central axis varies between two and
six.Numerous neurons in apoptosis are visible(3).Parafin section.Reduced silver nitrate Nonidez`s block method.Microphotos by
Nikon Digital Sight DS-Fi1 Hight- Definition Color Camera Head. x140 (I); x280 (A-H).
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Romanian Journal of Legal Medicine Vol. XXII, No 1(2014)
Figure 4. Neurons phenotyping based on microanatomic and space location criteria. 1. Satellite cell; 2. Intracapsular short
dendrites; 3. Perikaryon capsule; 4. Perikaryon; 5. Pericapsular neurofibers; 6. Space between neuronal capsules; 7. Terminal end
of short intracapsular dendrite; 8. Short extracapsular dendrites; 9. Neurofibers network around neurons; 10. Simple intracapsular
glomerulus; 11. Composed extracapsular glomerulus; 12. Extracapsular branches short dendrites; 13. Bineuron glomerulus; 14.
Multineuron glomerulus; 15. Neurofiber fascicles around glomerulus.Parafin section. Reduced silver nitrate Nonidez`s block
method . Microphotos by Nikon Digital Sight DS-Fi1 Hight - Definition Color Camera Head. x280 (J-N); x 420 (A-I); x 700 (C).
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Romanian Journal of Legal Medicine Vol. XXII, No 1(2014)
Figure 5. Microanatomic markers for phenotype changes involving neuronal structures inside superior cervical sympathetic
ganglion. 1. Short extracapsular dendrites; 2. Perikaryon; 3. Nucleus of neuronal body; 4. Lipofuscin granules condensed in
two perinuclear groups; 5. Crown of lipofuscin granules around nucleus; 6. Neurofibers around blood vessels; 7. Ovoid shape
dispersion of lipofuscine granules inside neuroplasma; 8. Lipofuscin granules arranged in a crescent fashion inside neuroplasma;
9. Lipofuscin granules near neuron membrane; 10. Chaotic dissemination of lipofuscin granules inside a neuron in apoptosis;
11. Neuron in apoptosis; 12. Neuron with pericapsular dendrites; 13. Pericapsular axonal elongations sectioned longitudinally;
14. Pericapsular dendrites; 15. Axonal terminations sectioned oblique; 16. Dendrites nest; 17. Ovoid axonal nest sectioned
tangentially; 18. Spherical axonal nest.Parafin section. Reduced silver nitrate Nonidez`s block method. Microphotos by Nikon
Digital Sight DS-Fi1 Hight – Definition Color Camera Head. x 420 (G; K – O); x 630 (H); x 700 (A-F; I; J).
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Figure 6. Location and relation of stem-like cells inside regeneration glomerulus. 1. Dorsal root of Spinal nerve and Dorsal root
Ganglion; 2. Sympathoblast cells aggregated in a rosette shape in dorsal root ganglion; 3. Perikaryon; 4. Axonal terminations; 5.
Stem -like cells; 6. Dendrites terminations; 7. Neuron in apoptosis; 8. Capsule around perikaryon; 9. Short extracapsular dendrites;
10. Subcapsular space. Parafin section. Reduced silver nitrate Nonidez`s block method. Microphotos by Nikon Digital Sight DSFi1 Hight – Definition Color Camera head. x 140 (A); x 280 (E); x 420 (B-D ; F).
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Romanian Journal of Legal Medicine Through minute dissections, Haller (1751)[8] visualized the
connecting communicating branches between sympathetic
ganglion chain and cranial and spinal nerves. Winslow
[9] introduces the term “great sympathetic nerve” and
Bichat [10] names it “nervous system of vegetative life”. The
diversification of microanatomic methods for the study
and research of neuronal system structures allowed a better
evaluation of the structural elements forming sympathetic
ganglion system. His (1890) [11] proved the axons
originated in neuroblast cells. Golgi (1886) [12] and Cajal
(1889) [13] visualized the neuronal system structures using
argentic nitrate impregnation and elaborated the neuronal
theory of neuronal elements discontinuity. Marinesco
(1906) [14] brings his contribution to the histochemical
study of neurons. Sherrington (1897) [15] introduced the
term synapse for the interneuronal contact areas. Loewi
and Dale (1936) [16] proved the presence of acetylcholine
at the neuromuscular junction and inside the synapses
of vegetative ganglions. Erlanger and Gasser (1944) [17]
established the criteria for the functional differentiation
of neurofibers. Henle (1876)[18] noticed the vasomotor
proprieties of sympathetic system and Claude Bernard [19]
established the capacity of stimulating secretions. Cohen
(1972)[20] and Levi Montalcini and Hamburger (1951)
[21]; Levi Montalcini and Booker (1960) [22] contributed
to the knowledge of neuronal growth factor (NGF).
Brenner, et al. (1989) [23] studied the genetic regulation
processes of the development of bio system structures and
the apoptosis phenomena. Extensive studies were carried
out for the knowledge of migration and differentiation
Nicole Marthe Le Douarin (n. 1930, Lorient, France)
Vol. XXII, No 1(2014)
of neural crest cells (Le Douarin et al., 1981 [24]; Le
Douarin and Dupin, 1993 [25]; Perris et al., 1991 [26]).
B. Observations on the microanatomic features of
superior cervical sympathetic ganglion
1. Determining factors for the variability of superior
cervical sympathetic ganglion
The diversification of immune histochemical and
molecular biology research methods lead to their use in the
study of the functional anatomy of sympathetic ganglion
system and equally to the abandon of classic silver staining
methods elaborated by Golgi (1886) [12], Cajal (1889)
[13], Bielschowsky (1904) [27] and Nonidez (1939) [1, 2].
Applying the reduced silver method in the study of superior
cervical sympathetic ganglion we obtained a micro neural
anatomic evaluation of the variable space distribution and
phenotype of neurons, the neurovascular relations and the
markers for neuronal phenotype transformation. Based on
the results of our observations, we consider that phenotype
transformations involving the neuronal ganglion structures
can be evaluated by three important markers: space
distribution of dendrites and axons; location and dispersion
of lipofuscine granules inside perikaryons and neuronal
apoptosis.
Analyzing the shape and space distribution of
neuronal expansions, we noticed the existence of three
neuronal phenotypes: a) neurons with short dendrites
located either inside the capsule (Fig. 4 A-C) or outside
(Fig. 4 D-F); b) neurons with long dendrites (Fig. 4 K, N);
Santiago Ramon y Cajal (1852 - 1934) Nobel Prize in
Physiolgie or Medicine , 1906
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Romanian Journal of Legal Medicine c) neurons with both types of dendrites (Fig. 4 N). Equally
we have seen three types of dendrites endings: fascicle
type, plexiform type (glomerular and/or dendrites crown)
and bundle type. The endings of long dendrites that form
fascicles of neurofibers have a variable trajectory and end in
“tufted” branches along the vascular and conjunctive spaces
(Fig. 1 E; Fig. 2 A-C). The branches of long dendrites create
glomerular plexuses outside the capsule (Fig. 4 J-N) and
sometimes they achieve the central axis of a construction
to which perikaryons attach, suggesting an architecture like
“bunch of grapes” (Fig. 3 A-I). The dendrites endings go
around the capsule of perikaryon and form a structure like
a bird’s nest that was first described by Retzius (1900) [28]
and confirmed by Cajal (1905) [29]. Around blood vessels
we identified neurofiber fascicles with variable trajectory”
tangent to external tunic, circumferential, oblique or parallel
to the longitudinal axis of arteries and veins (Fig. 2).
The location of lipofuscine granules inside
neuroplasma is extremely variable: isolated around nucleus
or adjacent to the perikaryon membrane; crescent or
dispersed in all the cytoplasm (Fig. 5 A-F).
2. Dendrites glomerulus – location for “stem-like cells”
On the serried sections through superior
cervical sympathetic ganglion, we identified the dendrites
glomerulus that contains compartments limited by
dendrites ramifications (Fig. 6). Those create a network
with wide spaces holding apoptotic perikaryons together
with islands of spheroid cells, with hyper chromatic
nucleus and delicate, argentic expansions, resembling stem
cells (stem-like cells) that migrated from neural crest. In
mammals, it is considered that the cells of neural crest are
stem cells that generate neuronal cells after their changing
into sympathoblast cells. The expression of stem cells
differentiation capabilities starts when they reach their
final location (Bronner-Fraser and Stern 1991) [30], in our
case that being superior cervical sympathetic ganglion. The
formation of sympathetic ganglion chain starts at 9 mm
length human embryos (Keibel and Mall, 1912) [31]. Stem
cells migrate from neural crest to sympathetic ganglions;
they lose their cytoplasmic expansions, take a spheroid
shape and become sympathoblast cells – small cells with
hyper chromatic nucleus (Page et al., 1986) [32]. Lately they
differentiate and create neurons and glial cells (Kirian and
Vatsala, 1996) [33] under the influence of insulin like nerve
growth factor (Le Douarin and Smith, 1988) [34]. They
ensure the perenity of phenotype and architectural changes
of neural sympathetic ganglion structures.
C. Implications in pathology
1. Clinical correlations
The results of our observations raise problems of
understanding the perenity of phenotype transformations
involving the neuronal structures inside sympathetic
ganglion system in correlation with age, sex and medical
history. Cardiologic clinical semiology drew the attention
on the variable activities of autonomous nervous system in
relation to sex and age of the patient (Gandhi and Singh,
Vol. XXII, No 1(2014)
2012) [35]. Anatomic and clinical studies proved the
existence and the magnitude of neuroaxonal dysfunctions
in relation to medical history: Alzheimer disease, cerebral
stroke, myocardial infarction, arterial hypertension, chronic
renal insufficiency, neoplasm (Pamela Parker Jones et al.,
2004) [36]. Equally, it has been proved the existence of
different types of reactivity of sympathetic nervous system
in close correlation to metabolism, age and psychomotor
activities (Schmidt et al., 1990) [37].
2. Biological model of dysfunction of the autonomic
nervous system in schizophrenia
The autonomic nervous system (ANS) is
responsible for homeostasis in brain and anatomical and
biological integrity. The two major divisions of the ANS, the
sympathetic and parasympathetic may be dysfunctional by
neurodevelopmental aggression for schizophrenic brain and
neurotoxicity and decreased neuroprotection consecutive
antipsychotic treatment. Transmission and sympathetic
ganglia in this study is represented by superior cervical
ganglia. This ganglion is responsible for pupillary light reflex
and heart rate. Heart rate variability in stress condition is a
potential marker for cardiac risk and arrhythmic marker for
cardiotoxicity determined by antipsychotics (Tümüklü et al.,
2008) [38]. This variability of heart rate consecutive of ANS
dysfunction may be a clinical marker in sudden death risk
in patients with schizophrenia and long-term psychotropic
drugs (Cohen et al., 2001) [39]. Autonomic nervous
system dysfunction in schizophrenia can be highlighted by
electrodermal and pupillography abnormality (Zahn et al.,
1991)[40]. Autonomic activity is disrupted by neuroleptic
effects and indicates cardiac risk in schizophrenia (Jindal et
al., 2005) [41]. Cardiac risk is correlated in schizophrenia
with obesity and metabolic syndrome, the dysfunction of
ANS disrupting brain connectivity of sympathetic system
in hypothalamic structures and induces endotheliumdependent vasoconstriction with high risk for myocardial
infarction and stroke. In schizophrenia the ANS dysfunction
is confirmed by evidences and it can be revealed anterior
to antipsychotic treatment, being a risk marker for this
treatment, or consecutive antipsychotic treatment and could
be a risk marker for cardiac risk, metabolic syndrome and
sudden death. Post-mortem studies for cervical ganglion
can be useful in forensic and medical expertise.
CONCLUSIONS
1. The structural stability of a system is permanently
dependent of the process of genesis, evolution and apoptosis.
These three phenomena coexist in time and space inside
superior cervical sympathetic ganglion and their congruency
ensures the perenity of anatomic and functional integrity for
autonomous neuronal system considered as a whole.
2. The determining factor of the perenity of
phenotype changes involving the neuronal ganglion
elements is the presence of stem cells migrated from embryo
neuronal crest.
3. The heterogeneity of space distribution of
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Romanian Journal of Legal Medicine axons, long and short dendrites determines a characteristic
architecture of superior cervical sympathetic ganglion
related to regenesis and evolution of its structures.
4. The location for regenesis processes is the
dendritic glomerulus that incorporates “stem-like cells” in
the compartments created by dendrites branches belonging
to at least two adjacent neurons.
Vol. XXII, No 1(2014)
5. The accumulation, space location and
disappearance of lipofuscine granules precede and
accompany the apoptotic changes of perikaryons.
6. The process of apoptotic transformation of neuron
takes place in the presence of permeable blood vessels that
are in contiguous relations to neurofiber fascicles.
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