Reticular formation and spinal cord injury.
ABSTRACT Compact literature review to provide basic knowledge of the reticular formation (RF) for clinicians.
The anatomical findings were collected from very recently published and well-edited books on neuroscience instead of hundreds of articles that contain materials still requiring test of time and difficult for busy clinicians to digest. Other individual references on specific issues such as a micturition centre, source of sildenafil citrate and so on are added. Clinical considerations discuss commonly encountered problems of spinal cord injury service and science. Every clinical condition is discussed in conjunction with the anatomy and physiology of the RF.
This section involves anatomy. (1) The core RF is located in the brain stem. The RF proper is divided into three longitudinal zones: the lateral (sensory), the medial (motor) and the midline (all others) zone. The midline zone is essential for wakefulness and consciousness. (2) Other brain stem structures sharing functions of the RF proper: periaqueductal grey (PAG), red nuclei, inferior olivary nucleus and precerebellar nucleus. PAG is almost related to all functions of the central nervous system, whereas the others are more connected to cerebellar functions of movements. (3) Spinal cord RF is located in the intermediolateral zone. It sends ascending and receives descending signals to coordinate and modulate motor, sensory and other functions.
This section involves clinical consideration. Multisystem damage, muscle contraction, upper urinary tract, sexual behaviour, skin trophic, pain, sleep apnoea, cross-system damages, spinal cord repair and comprehensive management are discussed to enlighten the clinical importance of the RF.
- SourceAvailable from: Riffat Mehboob[Show abstract] [Hide abstract]
ABSTRACT: Experimental studies have demonstrated that breathing activity in rats is generated early in embryonic stages in rostral spinal cord, precisely in the intermediolateral nucleus, then establishing a spinal cord-brainstem network. In this study we aimed to individuate and to define the developmental steps of the intermediolateral nucleus, still inadequately known in humans, in the thoracic spinal cord of a large series of perinatal and infant death victims, aged from 17 gestational weeks to 10 months of life. Besides we investigated a possible link between alterations of this nucleus and sudden unexplained perinatal and infant death. The normal developmental pattern of the human intermediolateral nucleus consists of a progressive maturation of its neurons, that change from a round to a polygonal shape with long axons and significantly decrease in number. Various degrees of intermediolateral nucleus hypodevelopment (neuronal immaturity in a normal structure/hypoplasia/agenesis) were found almost exclusively in unexplained fetal and infant death victims. Besides, a significant correlation was found between maternal smoking in pregnancy and the neuropathological results. In conclusion this work underlines the negative effects of prenatal nicotine exposure on the development of autonomic nervous centers checking the vital functions, already in early gestational stages, when the integrity of the intermediolateral nucleus is indispensable for the first breathing bursts.International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 04/2010; 28(2):133-8. · 2.03 Impact Factor
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ABSTRACT: Individuals with spinal cord injury (SCI) commonly complain about difficulty in sleeping. Although various sleep disordered breathing definitions and indices are used that make comparisons between studies difficult, it seems evident that the frequency of sleep disorders is higher in individuals with SCI, especially with regard to obstructive sleep apnea. In addition, there is a correlation between the incidence of sleep disturbances and the spinal cord level injured, age, body mass index, neck circumference, abdominal girth, and use of sedating medications. Regulation of respiration is dependent on wakefulness and sleep. Thus, it is important to be aware of basic mechanisms in the regulation and control of sleep and awake states. Supine position decreases the vital capacity in tetraplegic individuals, and diminished responsiveness to Pa(CO)(2) may further decrease ventilatory reserve. There also may be a potential disparity between daytime and nocturnal ventilation, as individuals with partially reduced muscle tone are susceptible to not only sleep apnea, but also sleep-related hypoventilation which may be aggravated during rapid eye movement sleep.Respiratory Physiology & Neurobiology 10/2009; 169(2):165-70. · 2.05 Impact Factor
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ABSTRACT: Despite clinical importance of identifying exact anatomical location of neural tracts and nuclei in the brainstem, no neuroimaging studies have validated the detectability of these structures. The aim of this study was to assess the detectability of the structures using three-dimensional anisotropy contrast-periodically rotated overlapping parallel lines with enhanced reconstruction (3DAC-PROPELLER) imaging. Forty healthy volunteers (21 males, 19 females; 19-53 years, average 23.4 years) participated in this study. 3DAC-PROPELLER axial images were obtained with a 3T-MR system at four levels of the brainstem: the lower midbrain, upper and lower pons, and medulla oblongata. Three experts independently judged whether five tracts (corticospinal tract, medial lemniscus, medial longitudinal fasciculus, central tegmental and spinothalamic tracts) and 10 nuclei (oculomotor and trochlear nuclei, spinal trigeminal, abducens, facial, vestibular, hypoglossal, prepositus, and solitary nuclei, locus ceruleus, superior and inferior olives) on each side could be identified. In total, 240 assessments were made. The five tracts and eight nuclei were identified in all the corresponding assessments, whereas the locus ceruleus and superior olive could not be identified in 3 (1.3%) and 16 (6.7%) assessments, respectively. 3DAC-PROPELLER seems extremely valuable imaging method for mapping out surgical strategies for brainstem lesions.Journal of neuroimaging: official journal of the American Society of Neuroimaging 04/2013; · 3.36 Impact Factor
Reticular formation and spinal cord injury
National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, UK
Materials and methods:
well-edited books on neuroscience instead of hundreds of articles that contain materials still requiring
test of time and difficult for busy clinicians to digest. Other individual references on specific issues such
as a micturition centre, source of sildenafil citrate and so on are added. Clinical considerations discus
commonly encountered problems of spinal cord injury service and science. Every clinical condition is
discussed in conjunction with the anatomy and physiology of the RF.
This section involves anatomy. (1) The core RF is located in the brain stem. The RF proper is
divided into three longitudinal zones: the lateral (sensory), the medial (motor) and the midline (all
others) zone. The midline zone is essential for wakefulness and consciousness. (2) Other brain stem
structures sharing functions of the RF proper: periaqueductal grey (PAG), red nuclei, inferior olivary
nucleus and precerebellar nucleus. PAG is almost related to all functions of the central nervous system,
whereas the others are more connected to cerebellar functions of movements. (3) Spinal cord RF is
located in the intermediolateral zone. It sends ascending and receives descending signals to coordinate
and modulate motor, sensory and other functions.
This section involves clinical consideration. Multisystem damage, muscle contraction,
upper urinary tract, sexual behaviour, skin trophic, pain, sleep apnoea, cross-system damages, spinal
cord repair and comprehensive management are discussed to enlighten the clinical importance
of the RF.
Spinal Cord advance online publication, 26 August 2008; doi:10.1038/sc.2008.105
Compact literature review to provide basic knowledge of the reticular formation (RF)
The anatomical findings were collected from very recently published and
Keywords: reticular formation; multisynaptic connections; coordination and modulation; SCI compli-
cations; comprehensive management; spinal cord repair
Reticular formation (RF) is an extremely important part of
the human central nervous system (CNS). It offers basic
support for life and health, without which diseases and
complications inevitably occur and aggravate. Its destruction
at high cervical level and above causes death. Despite its
utmost importance, it is much less known, understood,
taught and discussed than the somatic and autonomic
Neuroscientists have spared no effort on studying it
intensively and extensively for the past 50 years. A recent
electronic search of references of the past 20 years using the
keyword ‘Reticular Formation’ located around 3500 articles.
It speaks volumes of the magnitude of its importance. This
review has been undertaken to provide clinicians with some
basic knowledge of the RF without overloading them with
too many neuroanatomical details.
After spinal cord injury (SCI), the following phenomena
are observed in order of degree of threat to life and health.
1. Lack of wakefulness in high cervical lesions.
2. Malfunctions of viscerae and vascular systems.
3. Increased muscle tone (spasticity).
4. Hypersensitivity (pain).
5. Impairment and loss of sensation.
6. Impairment and loss of voluntary movement.
More often than not, the last two groups catch most
attention of general public, patients and even biomedical
professionals, because loss of voluntary movement and
sensation is immediately visible and palpable, whereas
understanding of the first four groups requires in-depth
knowledge of their underlying neuroanatomy and neuro-
physiology, which may not be adequate for many people. Of
the first four, the second group of phenomena is known to be
Received 8 April 2008; revised 19 June 2008; accepted 13 July 2008
Correspondence: Professor D Wang (retired), National Spinal Injuries Centre,
Stoke Mandeville Hospital, 11 Selkirk Avenue, Aylesbury, Buckinghamshire,
HP19 9QD, UK.
Spinal Cord (2008), 1–9
& 2008 International Spinal Cord Society All rights reserved 1362-4393/08 $30.00
related well to malfunctions of the autonomic systems.
However, the regulating role of the RF is not sufficiently
No system works in isolation in a living organism. Even a
simple contraction of a single muscle works in the following
highly coordinative way.
1. Contraction needs a complex mechanism of sensory
inputs to trigger it.
2. The contraction itself involves a series of complex
3. The antagonist muscle must relax.
4. The arterial supply must increase to transport more
oxygen and nutrients to meet the energy needs.
5. The vein drainage must also increase to remove resultant
Obviously, these can happen only when there is a central
mechanism coordinating all these aspects with enormous
complexity and accuracy. It is now known that the functions
of the entire nervous system are controlled by a special part
of the CNS known as the RF. It is the ‘Command Centre’ of
the CNS.1It controls the entire CNS through coordination
and modulation, without which, the above-mentioned
problems of SCI will inevitably occur. Unfortunately, such
an important system of the human CNS is far from familiar
to clinicians. This has prompted the need of this review.
Materials and methods
Anatomical findings are collected basically from some very
recently published and well-edited books on neuroscience
and SCI science instead of hundreds of articles that contain
materials still requiring test of time and difficult for busy
clinicians to digest.1–14The rest are individual references.
The discussion is based on common knowledge of the SCI
scientific community in connection with anatomical find-
ings of the RF. Clinical conditions such as multisystem
damages, muscle contraction, lower urinary tract problems,
skin trophic, pain, sleep apnoea, cross-system changes,
spinal cord repair and comprehensive management as a
whole are discussed in conjunction with the anatomical
findings of the RF.
What is RF?
Although the RF first received attention of Cajal15as early as
1909, it had not been studied adequately until recently.
Classical neuroanatomy focuses attention on neurons with
one axon, one long tract, one synapse, one neurotransmitter
and one target neuron. The RF is different. It is mostly
composed of another type of neurons, known as the
interneurons (neurons between neurons), that have poly-
synaptic connections (Figure 1).1,10Each of these neurons
has more than one axon, which go in different directions.
Every interneuron connects with many secondary inter-
neurons (primary connections). Many secondary neurons
connect with even more interneurons (secondary connections).
This process goes on and the number of connections
increases geometrically and finally reaches astronomical
figures of more than trillions. These connections form a
network-like system, hence the name RF.15
The astronomical number of connections of the RF has
made complete severance of their connections almost
impossible unless the relevant part of the CNS is completely
destroyed. This is why the system can hardly be studied by
traditional degeneration method. As a result, it had never
been properly studied and understood until recently when
new techniques such as electron microscopy, axon tracing,
intracellular labelling, transmitter histochemistry, electro-
physiology, advanced imaging and so on appeared during
the past five decades. These techniques have immensely
enhanced our knowledge of neuroanatomy, or more accu-
rately, functional neuroanatomy.
In addition to the basic net-shaped multisynaptic inter-
neuron connections, the RF has other distinct features.1,10
1. Its neurons are deeply located.
2. Its neurons are scattered and poorly defined and therefore
it is difficult to name some small clusters of neurons as
nuclei (Figure 2).
3. A single neuron may contain both ascending and
descending components (Figure 1).
4. All its components contain crossed and uncrossed
It is a misconception that neurons of the RF are located
only in the brain stem. In fact, they also extend down
through the entire length of the spinal cord.1
interneuron. The axons of the interneuron project in different
directions. (Courtesy of Siegel A and Sapru HN. Essential Neuro-
science. Lippincott Williams and Wilkins: Philadelphia, London,
Tokyo, Hong Kong, 20067–12. The annotations in italics are the
The difference between an (a) ordinary neuron and an (b)
Reticular formation and spinal cord injury
On account of the enormous difficulty in mapping out the
exact pathways of trillions of interneuron connections,
neuroscience has roughly worked out the destinations of
the RF neurons by using advanced techniques. These
techniques are able to locate both the action and the target
neurons but the exact pathways between them may not be
fully known. We are not discussing techniques that are not
clinically directly relevant. Of the other techniques, electro-
stimulation has been a classical method for more than a
century that does not need much discussion, whereas
advanced imaging techniques are too complex to describe
herein and important facts are still sketchy. However, there is
already abundance of knowledge of neurotransmitters.2,7
They are clinically highly relevant and merit special
Commanding adequate knowledge of neurotransmitters is a
lifetime career for a specialist. Therefore, this review only
offers a list of neurotransmitters for basic information
Neurotransmitters can also be hormones that are directly
released into the blood stream and trigger neurons or other
cells to work where there are relevant receptors. Thus, the
classical distinction between neurotransmitters and neuro-
hormones is blurred. It can be seen from the table that one
area or one type of neuron may release more than one type
of neurotransmitters whereas one type of neurotransmitter
can be synthesized by more than one area or one type of
neurons. Therefore, the strict rule of one type of neuron
connected with one type of neurotransmitter is no longer
Basic morphology and functions
The core of the RF is located in the brain stem with
connections over the entire CNS. When Cajal15introduced
the term reticular formation in 1909 and even decades later,
neuroscientists were not fully aware of its exact functions.
Hence the name was solely based on morphology. In fact,
there are other structures that are not net-shaped but share
the functions of the RF of coordination and modulation.
Functionally, they should be classified as one group that
consists of three parts.1,10
1. Brain stem RF proper.
2. Regions in the brain stem that are closely related to RF:
periaqueductal grey matter (PAG), red nucleus and
inferior olivary nucleus. They cannot be named morpho-
logically as RF because they are compact nuclei.
3. Spinal cord RF.
Brain stem RF
Complex connections between the RF and cranial nerves are
not discussed herein because they are not major concerns of
SCI. There is no need for clinicians to know all the complex
names of individual RF nuclei. Knowledge of groups of
neurons according to their longitudinal arrangements would
suffice. These arrangements are in line with their functions
and are hence easy to memorize. From the lateral aspect
towards the midline, the nuclei of the RF and their functions
are arranged in the following order (Figure 3).
1. Lateral: parvocellular (small cell) zone, afferent and
2. Paramedian and medial: magnocellular or gigantocellular
(large cell) zone, efferent and motor.
3. Median or midline zone: raphe nuclei, wakefulness and
bouring cranial nerves and the spinal cord through the
spinoreticular tracts. The signals are in turn transmitted to
This area receives afferent fibres from neigh-
stem RF. The most lateral strips on both sides are the lateral zones.
Along the midline is the median or raphe zone. In between is
the paramedian or the medial zone. (Courtesy of Patestas MA and
Gardner LP. A textbook of neuroanatomy. Blackwell Publishing,
20061–6) RF, reticular formation.
The longitudinal arrangement of zones of the brain
inferior olivary nuclei. (Courtesy of Patestas MA and Gardner LP. A
textbook of neuroanatomy. Blackwell Publishing, 20061–6. The arrows
are the author’s.) RF, reticular formation.
The disseminated locations of the RF neurons and the
Reticular formation and spinal cord injury
the paramedian or medial zone to modulate motor func-
tions. Other collaterals ascend to the thalamus to modulate
sensation or project to other higher centres (hypothalamus,
limbic system) through the median zone to sustain wakeful-
ness and to modulate autonomic functions.
Paramedian or medial zone.
reciprocal connections with almost all movement-related
structures of cerebral cortex, diencephalons, basal ganglia,
cerebellum and spinal cord. These connections contribute to
the coordination of both voluntary and involuntary move-
ments and adjustment of muscle tone. A special group of
large cells, known as the nucleus gigantocellularis, gives rise
bilaterally to medullary (lateral) reticulospinal tract. It
suppresses extensor spinal reflexes to the spinal motor
Neurons of this zone have
neurons. Two other groups of cells known as nucleus pontis
oralis and nucleus pontis caudalis project ipsilaterally to the
spinal cord motor neurons and facilitate extensor spinal
reflexes. The tract is named pontine (medial) reticulospinal
tract.1,3,8,10The balance between inputs of the two tracts
keeps the normal muscle tone in movement.
Median or midline zone.
There are two basic types of
1. Serotoninergic neurons project to higher centres and are
crucial to wakefulness and sleep. Damage to these
neurons or lack of inputs may lead to diminished or loss
2. Other neurons that synthesize enkephalin and b-endor-
phin project downwards to both spinal trigeminal nuclei
Classification and names of major neurotransmitters
Description of neurotransmittersAnatomical locationsFunctions
Acetylcholine Somatic and parasympathetic motor neurons,
myoneural junction, autonomic system and all major
regions of the CNS, including RF
Muscle contraction, functions of the autonomic
system and all major regions of the CNS,
Excitatory amino acids
Glutamate, precursor of GABA
Almost all regions of the CNS
Almost all regions of the CNS
Excitation, excitotoxicity - cell death.
Glutamate is stronger
Inhibitory amino acids
Most parts of the CNS
All body fluids, spinal cord, lower brain stem, retina
Inhibition, intermediate in protein metabolism
Basal ganglia and limbic system
Sympathetic neurons, locus ceruleus of the pons
Muscle tone and mental status
Mental status, exact mechanism unclear
Raphe or midline nuclei of the brain stemWakefulness and sleep
HistamineHypothalamusEndocrine and autonomic functions
Spinal cord motor neurons, autonomic ganglia
Not fully investigated
Not fully understood
Spinal cord, hypothalamus
Spinal cord, raphe nuclei, striatum, limbic system,
Spinal cord, hypothalamus, amygdale, limbic system
Many locations in the brain and spinal cord
Major pain suppressor
Nociceptin (Orphanin FQ)
Pain enhancement and many others
Substance PTrigeminal and dorsal ganglia, spinal cord,
Nitric oxide Hippocampus and many other regions of the brainMemory, wakefulness and sleep, neuroprotective
to neurotoxic and many more. New discoveries
are emerging fast
Abbreviations: CNS, central nervous system; GABA, g-amino-butyric acid; RF, reticular formation.
Reticular formation and spinal cord injury
and spinal dorsal horn nuclei to modulate and suppress
Other RF-related brain stem areas
Periaqueductal grey matter has reciprocal connections with
cerebral cortex, hypothalamus, limbic system, RF nuclei
within the brain stem and the spinal cord (Figure 5). Such
extensive connections indicate its extremely important role
of coordinating and modulating functions of the autonomic
and endocrine systems, emotion, memory and nociception.
Its neurons project to spinal cord through magnocellular
zone of pons and medulla. Recent studies have shown that
they might also send signals directly to the spinal cord. Of
these pathways, much attention has been focused recently
on micturition control.16–18It remains to be seen if it is more
important than the pons micturition centre (Barrington
nuclei).19In a combination of all its connections, PAG could
be the most important processing centre of all signals except
those from the red nucleus motor system for skilled move-
ments of upper limbs.
Red nucleus projects to cerebellum through inferior
olivary nucleus and precerebellar nucleus (Figures 2 and 4).
Red nucleus has reciprocal connections with both motor
cortex and cerebellum. Its final common path after cerebral
and cerebellar inputs is the rubrospinal tract. It is highly
developed in lower animals such as, cat but reduced to a thin
tract below cervical level in humans, in which it mainly
discharges flexor muscles of the upper limb.
of CN III
Publishing, 20061–6. The arrows are the author’s.)
The periaqueductal grey (PAG) and the red nuclei. (Courtesy of Patestas MA and Gardner LP. A textbook of neuroanatomy. Blackwell
(Courtesy of Encyclopedia Britannica, 2007. The arrows and the annotation of intermediolateral column are the author’s.) RF, reticular
Cross-section of the spinal cord to show the intermediate zone (RF) and the intermediolateral column (autonomic systems).
Reticular formation and spinal cord injury