Learning Objectives for this file:
1. CNS – neurotransmitters and functional brain regions 2. Tracts in spinal cord – afferent, efferent
3. CNS Blood Supply & BBB
Remember: we have a CNS & a PNS
FOR THE ABOVE DIVISIONS, REMEMBER THERE IS BOTH MOTOR AND SENSORY Motor:
• Impulses sent from the CNS to the periphery (the “efferent” or “descending” pathway)
• Control of the effector organs (muscle, glands) Sensory:
• Impulses sent from the periphery to the CNS (the “afferent” or “ascending” pathway)
• Sending information about the environment of the organs & tissues Afferent (sensory) &
Efferent (motor) pathways
PNS Multiple divisions
Somatic (Voluntary) ONLY Skeletal Muscle
ANS
(Involuntary)(Two divisions)
• Smooth & cardiac muscle
• Glands
Sympathetic NS
• Crisis response
• Fight or flight
• Catabolic
• Counter-regulatory
Parasympathetic NS
• Rest & repair
• Anabolic
• Regulatory
Enteric NS (gut)
CNS & PNS:
• CNS = brain + spinal cord
• PNS = somatic, autonomic (sympathetic & parasympathetic divisions), enteric
Central Nervous System:
• by definition, includes the brain + spinal cord
• the peripheral nerves lead out from the spinal cord at different vertebral levels and are named by this vertebral level, except at the very tail of the spinal cord, which breaks into the cauda equina
• these nerves are also called spinal nerves and exit the vertebral bones via the spinal foramina (foramen means window) -- note that nerves leaving the spinal cord AND entering the spinal cord (sensory nerves coming FROM the body) must use the same opening (foramen).
Impulse transmission & neurotransmitters:
• An action potential develops in one nerve cell, is propagated along the axon.
• To transmit information to the next neuron to to an effector organ, neurotransmitters are used to cross the synapse.
• The nerve cell must influence the membrane potential of the next cell, using a neurotransmitter, in order to transmit the impulse.
• The connection may be nerve-nerve, nerve-muscle, nerve-gland.
Neurotransmitters (NTs):
• chemicals synthesized in cell body (soma) of neuron, stored at end of axon at the synaptic terminal.
• They diffuse across the synaptic cleft (space).
• >60 identified chemical neurotransmitters
• How they work – receptor on receiving cell responds to the NT:
o some are only inhibitory – always cause inhibitory effect on post-synaptic cell o some are only excitatory – always cause excitatory effect on post-synaptic cell o some function either way (receptor response creates either excitatory or inhibitory
effect, depending on the cell and the tissue type)
Are ALL NTs going to act the SAME at the post-synaptic neuron? NO:
• Excitatory neurotransmitters and EPSP:
o influence the next cell in the relay to move towards threshold (closer to an action potential), depolarizing the post-synaptic and bringing it closer to threshold and action potential
o This depolarization is called an excitatory postsynaptic potential (EPSP), but it is not enough to make the next cell reach threshold & firing all by itself.
o Many excitatory neurotransmitters affecting the next cell can do this by their combined depolarization effects.
• Inhibitory neurotransmitters and IPSP:
o cause the postsynaptic neuron or effector cell to develop an inhibitory postsynaptic potential (IPSP), which brings the cell membrane potential further away from threshold.
o This is called hyperpolarization (the opposite of depolarization), making the resting membrane potential more NEGATIVE & taking it further away from threshold & firing.
o It will now be MORE difficult to stimulate this cell to action
An EPSP brings the neuron CLOSER to threshold and action potential:
An IPSP brings the neuron AWAY from threshold:
Inhibitory Neurotransmitters Causing IPSP:
• An inhibitory stimulus brings the resting potential further away from the threshold.
• Then, there is a longer distance to travel to actually reach threshold, meaning that
SUMMARY Overview of Neuron Functional Anatomy:
• The SOMA synthesizes neurotransmitter (NT) chemicals
• The NTs are shipped down the axon to be stored in the synaptic knobs on the end of the axon terminal.
• This neuron will synapse (meet up) with the next cell in line, called the post-synaptic cell
o The post-synaptic cell could be another neuron, or an effector “end” organ like cardiac muscle, smooth muscle, skeletal muscle, gland).
• The neuron receives input from the dendrites in the form of stimuli.
o If the stimuli are sufficient, an action potential develops, so that an electrical impulse travels down the axon (propagation of the impulse) to the axon terminal.
o When the impulse reaches the axon terminal, the impulse causes the release of neurotransmitters (NTs) from the synaptic knobs.
o These NTs then diffuse across the synaptic space and land on the next cell in line (the post-synaptic cell).
• This is how nerve-nerve, nerve-muscle, or nerve-gland communication occurs.
o Remember, the muscle or gland would be called an “effector organ” or “end organ.”
• NTs may result in an inhibitory OR an excitatory effect on the post-synaptic cell, determined by the neurotransmitter (NT) and by the RECEPTORS on that postsynaptic cell.
• Although there are a limited number of the typical NTs used by the body
(acetylcholine, norepinephrine, epinephrine, dopamine), the effect on the cells is determined by: the tissue type of the cell, and the receptors present on that cell.
Brain & Spinal Cord relationship:
• The brain normally inhibits the spinal cord
• The spinal cord is involved in reflexes that occur automatically outside of our conscious control
• The brain reduces this activity of the spinal cord
• Clinical correlates:
o Problems in the brain – stroke, dementia, cerebral palsy, etc. will result in greater spinal cord activity
o Clinically, we see “abnormal reflexes” that represent spinal cord reflexes that should have been suppressed! (e.g. Babinski) – called DISinhibition (i.e., removing the inhibition allows the reflex to become active)
o Infants who do not have completely developed brains yet will have “infant spinal reflexes” that are lost as the infant matures in the first 6-12 months of life – part of the physical assessment of the infant’s normal development
CNS Neurotransmitters (NTs):
• the CNS uses a variety of chemicals as neurotransmitters, some of them are chemicals found in other organs that do different things in those organs.
• For instance, vasoactive intestinal peptide (VIP) is used in the gut to modulate digestive processes, and it also serves as a neurotransmitter in the CNS.
• Clinical correlate:
o Destruction of dopamine secreting neurons in the substantia nigra area of the brain causes Parkinson's disease a relative dopamine deficiency.
o Since dopamine is inhibitory, lack of dopamine results in disinhibition (stopping of the normal inhibition) of reflexive spinal cord activity thus there is
OVERactivity of these pathways
o The overactivity of the spinal cord results in clinical findings of spasticity, rigidity, cogwheeling
o The lack of dopamine and the disinhibition of the spinal cord also reduces voluntary motor control.
o Treatment increases available dopamine by giving drugs like L-DOPA that are converted to dopamine in the brain.
How brain cells “change their tune”:
• New evidence that mitochondria in neurons actually migrate down the axon towards the synapse
• Presence or absence of mitochondria at the end of the axon may affect the ability of brain cells to release neurotransmitters
• See: https://www.nih.gov/news-events/news-releases/nih-researchers-discover-how- brain-cells-change-their-tune
Dopaminergic sites in CNS in the CNS, respond to dopamine and have dopamine receptors.
Often responsible for movement, sexual behavior and mood.
Some “projections” to the higher functional areas of the cerebral cortex as well.
Adrenergic sites in CNS
in the CNS (respond to epinephrine/EP and/or norepinephrine/NE). Often responsible for higher functions (cognition).
Serotonergic Sites in CNS respond to serotonin (5HT) and have serotonin
receptors (many 5HT subtypes). Often responsible for mood, nausea/vomiting, appetite, sleep (“lower functions” in the limbic area) -- but notice how these lower centers
“project” to the higher centers in the cerebral cortex and influence their function.
CNS NEUROTRANSMITTERS:
Warning!!!
• these are in the CNS – do NOT mix up with what we will study in the PNS o Amino acids (inhibitory & excitatory types)
o Acetylcholine (ACh)
o Monoamines (serotonin, epinephrine/norepinephrine, dopamine)
o “Other” (peptides, substance P, histamine, TRH, endocannabinoids, etc.)
It is all about balance:
• The amounts of neurotransmitters acting on the brain neuron receptors determines brain activity
• Very often, it is not the absolute amount of neurotransmitters, but the balance between them that causes neurologic disorders
Main NT categories in the CNS:
1) Amino Acids:
• Neutral Are Inhibitory:
o include glycine & GABA (gamma amino butyric acid -- with GABA-A & GABA-B receptors)
o Anxiolytics, sedatives, anti-epilepsy drugs enhance GABA action o Examples are benzodiazepines & phenobarbital
o the poison strychnine binds to glycine receptors muscle spasm & death
• Acidic Are Excitatory:
o glutamate (glutamic acid) uses G-protein linked enzyme receptors
• this is the main excitatory NT in the brain o aspartate (aspartic acid)
o Use ion channel receptors called NMDA
• implicated in Iearning – newer Alzheimer’s drugs affect this pathway
• excessive release implicated in development of amyotrophic lateral sclerosis (Lou Gehrig’s disease)
• implicated alcohol substance use disorder (alcohol SUD) relapse:
http://pubs.niaaa.nih.gov/publications/arh314/310-339.htm o Also use non-NMDA ion channel types.
2) Acetylcholine (ACh):
• use G-protein linked receptors called “cholinergic”
• the two types of cholinergic receptors (AChR) are nicotinic & muscarinic receptors.
• Cognitive pathways use Ach
o In Alzheimer’s disease there is death of neurons that make ACh (cholinergic neurons) – many drugs for this condition raise the level or activity of Ach .
• Acetylcholine activity in the brain may also interact with other pathways o Nicotine activity
• Stimulates dopamine release and activates the reward pathway
• Interact with other pathways that send projections to the prefrontal cortex
Nicotine stimulates ACh receptors that in turn result in release of other NTs that affect other brain areas due to projections to those regions
3) Monoamines:
• Implicated in pathogenesis of depression, psychosis, AD/HD.
• Dopamine:
o Synthesis: tyrosine (amino acid) dopa dopamine.
o Degradation: monoamine oxidase (MAO) & catechol-O-methyl transferase (COMT) enzymes.
o Receptors: dopamine (D) “dopaminergic” receptors
o Usually inhibitory but can also be excitatory – depends on the neural circuit o Important functions in emotions, attention/wakefulness, prolactin release
(pituitary pathways), movement (substantia nigra), emesis (chemoreceptors of the medulla controlling the central vomiting reflex), sexual excitation.
o Pharmacology for psychosis, depression, Parkinson's disease, ADHD.
o Dopamine clinical correlate – Parkinson’s disease:
Destruction of dopamine secreting neurons in the substantia nigra causes Parkinson's disease a relative dopamine deficiency.
Since dopamine is inhibitory, lack of dopamine results in disinhibition of reflexive spinal cord activity
The overactivity of the spinal cord results in spasticity, rigidity, cogwheeling
The lack of dopamine and the disinhibition of the spinal cord also reduces voluntary motor control.
Treatment increases available dopamine by giving drugs like L-DOPA that are converted to dopamine in the brain
Lack of dopamine prevents the normal “damping” effect on the reticular formation, resulting in increased muscle tension and causing tremor
• Dopamine clinical correlate – the dopamine “reward” pathway and addiction:
o Slide show: https://learngendev.azurewebsites.net/content/addiction/rewardbehavior/
o This pathway produces dopamine in response to stimuli that normally are pleasurable, such as food
o The same pathway is implicated in overeating, gambling, and substance use disorders (drug addiction); see (Gudriaan, Yucel & & van Holst, 2014) – gambling behaviors and the dopamine reward pathway:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033022/
• Serotonin (5-hydroxytryptamine, or 5HT):
o Inhibitory
o Receptors called “serotonergic” (5HTR)
o Affect regions in pons/brainstem, to regulate: sleep induction, mood & anxiety, temperature control, neuroendocrine system.
o A deficiency may cause depression
o An elevation in schizophrenia may cause hallucinations & delusional thinking.
• Norepinephrine (NE) and Epinephrine (EP):
o pathways in CNS not clearly known o Excitatory
• Increases focus
• Enhances executive functions (cognitive)
o Receptors are “adrenergic” receptors (named for the older name, adrenalin) o Hypofunction of NE pathways may cause depression, ADD/ADHD
o Normal Analgesic properties:
• EP works on presynaptic alpha-2 receptors in the spinal cord (substantia gelatinosa) and brainstem nuclei (periaqueductal and periventricular nuclei)
• Some drugs simulate this action as well – clonidine, dexmedetomidine o Lack of NE correlated with development of attention deficit disorder (ADD):
• Loss of normal NE effects causes distractibility
• Deficiency in locus ceruleus causes effects in the frontal cortex and limbic system
4) Neuropeptides & other NTs:
• Opiate Neuropeptides:
o Derived from cleaving (cutting into pieces) a very large compound called POMC (pro-opiomelanocortin), endogenous opiate types include enkephalins, endorphins, & dynorphins
o Act on opiate receptors
• The drug morphine acts on these same receptors o At the SAME TIME other chemicals are released
• ACTH (adrenocortical stimulating hormone – stimulates cortisol secretion from the adrenal cortex
• MSH (melanocyte stimulating hormone – stimulates melanocytes and skin darkening)
o THUS, there are additional byproducts of endogenous opioid production.
• Other Neuropeptides & NT systems:
o NOTE that many of these chemicals are also found OUTSIDE the CNS (e.g. in the gut) and yet function as neurotransmitters INSIDE the CNS
o Note that we are still unclear on the action in the brain of many of these neuropeptide NTs
o Examples:
• neurotensin, vasoactive intestinal peptide (VIP)
• substance P (involved in pain transmission)
• somatostatin, neuropeptide Y (stimulates food intake, synthesis inhibted by leptin from adipocytes)
• thyrotropin releasing hormone (TRH)
• histamine (hypothalamic thermoregulation, brain blood flow) o Endocannabinoid system (ECS):
• Cannabinoids (anandamide & 2-AG) stimulate CB1 and CB2 receptors
• Nice overview (Battista et al., 2012):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303140/
• Interacts with the endocrine system & immune system
• Implicated in metabolic regulation via neuroendocrine actions
• Implicated in stress and pain responses
• Implicated in overweight/obesity – when we exercise and feel less pain, we may be activating this system
• This system is more active in those with increased waist circumference and obesity; it is thought that chronic overeating (as well as tobacco use) results in a dysregulation of this system
• May interact with the system below
• More on this system in the Endocrine Unit o Orexin/Hypocretin system:
• These NTs were named by two different laboratories at the same time, so we have the two “names” – but it is only ONE neurotransmitter
• Made in the hypothalamus by “orexinergic” neurons
• This NT is implicated in wakefulness (being able to stay awake) and also stimulating appetite
• A deficiency would therefore cause sleepiness
• Narcolepsy is now being renamed “orexin/hypocretin deficiency”
• See: http://med.stanford.edu/narcolepsy/symptoms.html
• See: http://med.stanford.edu/narcolepsy/faq1.html
• considered an auto-immune condition, antibodies attack and kill the nerve cells that make orexin/hypocretin
• Diagnosis is accomplished with sleep history, polysomnogram (sleep latency testing) and lumbar puncture (spinal tap) to obtain cerebrospinal fluid (CSF) to test for orexin/hypocretin levels and auto-antibodies
• Some new sleep aid drugs are antagonists to this NT
OVERVIEW OF CNS = BRAIN + SPINAL CORD: Details later
• Receives almost 20% of cardiac output – THUS CONSIDERED A “VITAL ORGAN.”
• Embryologic development mimics phylogenic development: “ontogeny recapitulates phylogeny”
• Can really be considered as a special extension or upward outgrowth of the spinal cord (phylogenically as well as ontogenenically).
CNS:
• looking at the brain from the superior aspect, you can see a longitudinal fissure separating the left and right halves.
• looking at the brain from the side, you can identify separate discrete structures identified as
OVERVIEW – PARTS OF THE BRAIN:
• Forebrain:
o Telencephalon (cerebrum & basal ganglia)
o Diencephalon (thalamus – major sensory processing; hypothalamus, subthalamus, epithalamus – maintaining the internal environment; hippocampus – formation of new memories
The diencephalon includes the Limbic system = amygdala,
thalamus/hypothalamus/epitha-lamus/subthalamus, hippocampus (regulation of mood, sleep, feeding/sexual behaviors)
• Midbrain (mesencephalon):
o Red nucleus, substantia nigra, colliculi
• Hindbrain:
o Cerebellum, pons, medulla
A nice one-page internet review: https://courses.lumenlearning.com/boundless- psychology/chapter/structure-and-function-of-the-brain/
What is the BRAINSTEM?? a purely CLINICAL term
• WHAT IS IT??
• CNS that controls respiration & circulation with "centers"
• includes both the midbrain + hindbrain.
• This is a “made up” CLINICAL term – often used to lump together the vital autonomic functions of breathing & heartbeat – includes
o Midbrain: Mesencephalon (red nucleus, substantia nigra, colliculi)
o Tentorium cerebelli: meningeal structure divides midbrain from hindbrain.
Therefore, clinically, supra-tentorial = above the cerebellum, infratentorial is below.
o Hindbrain: Metencephalon (cerebellum & pons) & Myelencephalon (medulla)
CEREBRAL METABOLISM:
• Glucose is the usual substrate for energy production
• The RQ (respiratory quotient) is almost 1 a 1:1 relationship of oxygen consumed and carbon dioxide produced
o other substrates (mannose, maltose, keto-acids) can be used if deprived of glucose
o BUT – not all persons can utilize other substrates well, so always ASSUME glucose is the essential foodstuff for neurons and the nervous system
• Also, brain cells are totally dependent on aerobic metabolism o no stored glycogen or anaerobic metabolism
• Entry of glucose into the neurons is NOT dependent on insulin as it is in other cells
o Other related cells, such as retinal cells (which are really modified neurons) also are not dependent on insulin for glucose entry into the cells
o If a fetus, the fetal cells also are independent of insulin for glucose entry – they receive and process whatever glucose level the mother sends the fetus
• Clinical correlate:
o in hypoglycemia due to hyper-insulinemia, most available glucose FIRST enters the insulin-sensitive somatic/visceral cells
o this doesn't leave enough for the brain you see mentation changes leading to coma and brain death (can be rapid, irreversible).
o This is why tight diabetic management can be dangerous if using drug therapy (oral or injectable) & compliance to exercise/diet regimen with frequent SBG (self blood glucose) monitoring is paramount – current diabetes guidelines stress individualized targets of glucose for diabetic management (e.g., more relaxed targets in youth and the elderly) in order to avoid hypoglycemic events.
SPINAL CORD – THE DETAILS:
• long nerve cable starts at medulla, & ends at level L1/L2 of the bony vertebral column.
• Shorter than the vertebral column, but the cord still has named segments
corresponding to the bony vertebrae levels (cervical, thoracic, lumbar, sacral).
• Nerves leaving the end are called the Cauda Equina (horse's tail).
White Matter of the Cord: axons (white = myelin) of tracts.
Central Canal:
• travels throughout central portion of cord, this is the space that is left after the notochord of the fetus folds up to form the spinal cord and (cephalad) brain.
• It contains CSF & communicates with the IV ventricle of the brain.
Gray Matter of the Cord: contains neuron cell bodies (soma).
“Horns” of the Spinal Cord: bulging areas of the cord – dorsal, ventral, lateral horns.
• Ventral horn efferents:
o somatic motor outflow.
o Anterior bulges of the cord are called anterior "horns."
o The ventral gray horn has only soma (neuron cell bodies) of the efferent
motoneurons, which send out somatic motor neuron axons (to skeletal muscles of the somatic NS).
• Lateral horn efferents:
o autonomic motor outflow of the ANS (sympathetic & parasympathetic o sympathetic neurons at thoraco-lumbar levels
o parasympathetic neurons at cranio-sacral (cranial nerve + sacral spinal cord) levels
• Dorsal horn afferents:
o sensory neurons & tracts.
o Transmit afferent impulses from the body.
o Pain transmission fibers are at the tip of the dorsal horn (substantia gelatinosa).
• Unipolar sensory nerve central process axons enter the dorsal horn, synapse with the interneurons. The interneuron axons make up the ascending spinal sensory tracts for that particular sensation
More pictures below…
Anatomy of the Spinal Nerve: (also called the Trunk)
• REMEMBER that the VENTRAL part of the spinal cord is outflow to the somatic (voluntary skeletal muscle) peripheral nervous system, the DORSAL part of the spinal cord are the ascending sensory tracts (pathways), and the LATERAL part of the spinal cord is responsible for the autonomic pathways.
• NOTE that the nerves ENTERING (sensory) and EXITING (motor) the spinal cord must at
Another picture that might help – spinal reflex pathway loop (in and out):
• This shows the afferent sensory signal (from the finger) ascending to the dorsal horn of the spinal cord
• Then, an interneuron connects with the outgoing efferent motor nerve in the anterior horn that now travels to the descending (outflow) muscle, causing a contraction to pull the finger back from the pain
• This is a complete reflex arc
Anatomy including vertebral bones:
TRACTS OF THE SPINAL CORD: see also pictures next page Tracts are PATHWAYS transmitting a certain type of information:
• distinct regions forming the different nerve pathways or tracts (afferent & efferent), which are bundles of axons traveling together & serving the same function (e.g. pain &
temperature sensations).
• The spinal tracts are named from where they start where they end up !!
• Examples:
o corticospinal (cortex to spine, descending), spinothalamic (spine to thalamus, ascending)
• Dorsal ascending sensory tracts:
o Remember the tracts carrying the various sensations decussate differently.
o These sensory tracts may be somatic or autonomic
• Ventral & Lateral descending efferent tracts:
o May also be somatic or autonomic Decussation: “crossing over”
• many of these tracts “cross over” from one side to the other at some point in the cord.
• So, an outgoing efferent motor impulse may originate on the left side of the brain, but crosses over to the right and controls the right side of the body.
• Similarly, sensory afferent incoming signals from one side of the body decussates and ends up on the other side of the brain.
• Clinical correlate:
o “Contralateral” findings on physical exam of the body when brain tissue is damaged o destruction of brain tissue (stroke=CVA=brain attack) on the left causes motor
deficits on the right side of the body
Pyramidal (corticospinal): a descending MOTOR tract
• upper motor neurons (UMN) arise in cortex descends to cross over
• decussate at medulla (pyramids)
• synapse with lower motor neurons (LMN) in the ventral gray horn
• these send out axons (ventral white horn)
• somatic effectors (skeletal muscle)(synapse on the NMJ)
• called corticospinal (start in cortex, end up in spine)
Extrapyramidal: (outside of the pyramidal) ANOTHER motor tract
• originate from cerebral nuclei
• These don't always decussate like the pyramidal tract.
• They have names like rubrospinal (e.g. from red nucleus to the spinal cord)
o are usually involved in non-voluntary expressions of fine motor and postural control o these types of movements are called stereotypical (learned skeletal muscle
behavior like holding a pen and writing – you don’t have to think about it!!) o longterm administration of some drugs (e.g. phenothiazines) damages this area
and causes extrapyramidal syndrome (EPS) with stereotypical muscular actions
Motor Tracts
• are descending (Efferent)
• will decussate (cross over) at some point so that the impulse originating on one side of the brain has its muscle effects on the contralateral side of the body (for most motor tracts)
• Some are somatic and affect skeletal muscle (voluntary)
Sensory Tracts enter the Dorsal Root
See next page for entire pathway to brain
Sensory Tracts
• are ascending (Afferent)
• will also decussate (cross over) so that the incoming sensory signal from one side of the body will finally travel to the contralateral side of the brain, although the decussation can occur
BONY ANATOMY:
Vertebral column:
• 33 vertebrae
• 7 cervical, 12 thoracic, 5 lumbar, 5 fused sacral, and 4 fused coccygeal Cartilage:
• the intervertebral discs or the nucleus pulposus.
• Clinical correlate: The disk can rupture, causing a herniated nucleus pulposus (HNP).
• membranes called meninges with spaces above and below the membranes that also contain structures or fluid.
Traveling from OUTSIDE towards the INSIDE
• SPACE Epidural space: a POTENTIAL space above the first layer of meninges which has a NEGATIVE (subatmospheric) pressure; starts at foramen magnum & ends at sacrococcygeal membrane
o Epidural hemorrhage can occur here, often DELAYED after trauma
o Epidural anesthesia is done by instilling anesthetic into this space, which does not communicate up and down the spinal cord canal, and is therefore more localized, shorter acting, and safer.
• MEMBRANE Dura mater: ("tough mother") the first layer of meninge, includes both the periosteum (reflected against the skull bone) and the inner dura (meningeal layer).
o Falx cerebri: The inner dura (meningeal layer) gives rise to the falx cerebri, which divides the two brain hemispheres and anchors the brain to the skull.
• SPACE Subdural space: below the dura mater, contains blood vessels.
o Clinical correlate: bleeding here is a subdural hematoma.
• MEMBRANE Arachnoid membrane: the second layer of meninge. This layer contains the arachnoid villi that reabsorb the cerebrospinal fluid (CSF). The CSF flows in the space just below this membrane
• SPACE Subarachnoid space: this space forms the internal cavities of the brain (ventricles) – lateral ventricles (I & II), draining to III & IV ventricle and down into the central canal of the spinal cord. This space contains the cerebrospinal fluid (CSF), made in the meninge layer just below. The central canal is where the cerebrospinal fluid (CSF) flows in the spinal cord.
o Clinical correlates:
Lumbar puncture (spinal tap) taps the CSF by introducing a needle into this space. When tapping, pressure is checked, and the constituents of CSF (change with pathology). The pressure here is POSITIVE (5-15 mm Hg) and this is why the CSF leaks into a needle when lumbar puncture is performed.
Spinal anesthesia can also be performed by instilling anesthetic into this space. However, since this communicates up & down the spinal cord, it is longer acting & not as safe.
Subarachnoid hemorrhage (SAH) is the "worst headache of my life"
"thunderclap" (so-called critical headache symptom).
If bleed here, there will be "meningeal" signs of stiff neck and neurologic findings.
• MEMBRANE Pia mater: is the last meninge layer, and has the choroid plexuses that
Spinal meninges:
CNS BLOOD SUPPLY: See picture next page.
• Brain receives 20% of cardiac output (900 ml/min) – THUS IT IS A VITAL ORGAN
• Loss of blood flow causes coma in 5 - 10 seconds due to ischemia Brain blood supply:
• Common carotid arteries internal carotid arteries to base of skull into cavernous sinus divide into anterior and middle cerebral arteries.
• Subclavian arteries go through foramen magnum join together to form basilar artery
then divides to form the posterior cerebral arteries.
• Circle of Willis
o provides a circular arch for blood flow
o so that there is a continuous supply of blood to the brain via collateral circulation (even if a major contributing artery is blocked).
• Veins drain into venous plexuses and dural sinuses, eventually draining into the internal jugular veins at the base of the skull.
Pathology:
• Blockage could be thrombosis, tumor, bleeding or injury.
• Could be in either artery or vein.
• Arterial blockage or bleed causes ischemia, TIA, CVA.
• Venous blockage causes increased intra-cerebral pressure (intra-cranial) o Clinical: increased ICP with clinical sign of papilledema.
Spinal cord blood supply:
• Vertebral arteries branch off into anterior and posterior spinal arteries.
• The aorta branches to form anterior & posterior radicular arteries.
REGULATION (CONTROL) OF CNS PERFUSION:
• this is monitored and carefully regulated to keep CNS blood flow at correct levels
• the cerebrospinal fluid (CSF) is monitored for acid levels and oxygen levels
• ACIDITY:
o CO2 level is monitored, in the form of carbonic acid (remember carbonic acid buffer system with CO2 is in equilibrium with carbonic acid according to the pH of the system).
o More acid (any type) increases cerebral blood flow, to wash acid out of the brain (neurons can't function with acid environment).
o Monitoring chemoreceptors are located in the anterior medulla oblongata o Thus – increased CO2 or reduced pH causes increased blood flow
o The acidity/CO2 monitoring system is the most powerful regulator of cerebral blood flow
• OXYGEN:
o Reduced oxygen saturation causes cerebral vasodilatation plus increased blood flow
o This is a less powerful regulator.
• AUTOREGULATION OF CEREBRAL BLOOD FLOW:
o cerebral perfusion is held between 60 - 180 mm Hg, REGARDLESS of the systemic circulation pressure – it is said to be “independent” of systemic BP.
However, autoregulation can fail:
o Systolic BP < 60: cerebral hypoperfusion.
o Systolic BP > 200: cerebral hyperperfusion (vessels stretch/rupture) Relationship of cerebral blood flow (CBF) and carbon dioxide
Failure of autoregulation at hypotensive and hypertensive systemic systolic BP
Remember we are looking at the BOTTOM of the brain to see these structures.
CNS Blood Supply:
• the blood supply comes from both the anterior and posterior neck, rising up into the brain with two vessels anteriorly (carotids) and two vessels posteriorly (basilar)
• the blood supply then breaks into different cerebral arteries that serve different parts of the brain -- thus, lack of blood flow in a specific artery (thrombosis) or hemorrhage from a specific artery gives rise to clinical symptoms and signs that match the functions of that area of the brain (e.g. speech, motor function)
• also, the Circle of Willis that encompasses a circle around the base of the brain, connects
The famous BLOOD BRAIN BARRIER (BBB):
• everything in blood plasma doesn't get into CSF and the brain !!
• Once a substance gets into the CSF, the entire brain is exposed to the substance (e.g.
intrathecal drug injections)
• Barrier created by several factors:
o neuroglia (astrocytes -- supporting cells of the brain) that selectively absorb substances from the blood
o & the tight junctions between endothelial cells that make up the brain capillaries (brain capillaries are less "leaky").
• Brain areas WITHOUT the BBB:
o Pituitary, hypothalamus, pineal
o Why? in these areas, the brain needs to sample the body's internal environment for regulation of bodily functions.
What CROSSES the BBB – important clinically:
• Enters easily: similar to cell membrane rules
o lipid soluble (alcohol, anesthetic agents) -- lipophilic o water
o gases (carbon dioxide, oxygen).
• Difficult entry:
o Proteins o Electrolytes
o large molecules many therapeutic drugs (e.g. antibiotics) are protein bound in plasma & can't enter CSF.
o CLINICAL: difficulty in treating meningitis/encephalitis/cerebral abscesses & brain dysfunction (e.g. depression) – can’t get some chemicals into the brain.
THE BRAIN – THE DETAILS:
Functional Areas of The Brain
Named parts Of the Brain
FOREBRAIN (TELENCEPHALON & DIENCEPHALON):
• Telecephalon is the cerebral hemispheres and basal ganglia
• Diencephalon is the limbic system
Telencephalon:
1) Cerebrum (cerebral hemispheres) and basal ganglia (cerebral nuclei).
• Convolutions = gyri, grooves = sulci + fissures.
• Cerebral cortex = gray matter on top (neuron cell bodies) and white matter below (myelinated axons).
• Separation of left & right hemispheres, but corpus callosum connects them for intercommunication.
• Frontal lobe = conscious thought & recall memory.
2) Telencephalon Motor Output (Efferents) Centers & Tracts:
• Corticospinal (Pyramidal) Tract:
o motor neuron cell bodies in cortex send axons to spinal cord, they converge &
decussate in the medulla (where it looks like a pyramid on microscopic cross section).
o So, one side of the brain controls the contralateral side of the body.
o Responsible for gross motor function.
• Extra-pyramidal tract:
o motor tracts that go from cortex to spinal cord, but however are not in the pyramidal tract (are "outside" the pyramidal tract).
o Cortical premotor area – control of fine repetitive movements
o cerebral nuclei (basal ganglia) – fine tune motor control (= the putamen, nucleus caudatus, globus pallidus, amygdaloid body).
• Broca's area: motor aspects of speech.
3) Telencephalon Sensory Input (Afferents) Centers:
• Parietal area receives somatic sensory input, association fibers connect it to the motor &
other areas.
• Occipital lobe (visual cortex) is for visual receptive sensory input and visual memory.
• Temporal lobe handles auditory and associational tasks, long-term memory, balance, taste, smell, and speech reception & interpretation (Wernicke's area).
Diencephalon:
• Most afferents coming from the spinal cord end here.
• Includes limbic system, hypothalamus
• Limbic system = thalamus, hypothalamus, epithalamus, subthalamus.
• Limbic means "border" and the structures line the corpus callosum along the bottom of the cerebrum.
1) Thalamus:
• Considered a "relay center" for all parts of the CNS and "switchboard" for afferent impulses to the CNS -- afferents come in, there are upward and downward
interconnections to the Telencephalon.
• Emotional content of thoughts and emotional responses seem to reside here.
2) Hypothalamus:
• hypothalamus maintains homeostasis control (temperature, satiety) and controls the A.N.S. functions through both neural and endocrine pathways.
• Affects both behavior (feeding, sexual, reward/punishment) and involuntary visceral functions.
• Controls the master gland (pituitary) through feedback loops as well as being directly connected to the posterior pituitary.
• More on hypothalamic anatomy, structures, function, feedback, blood supply in ENDOCRINE module.
See pictures below…
LIMBIC SYSTEM
located around the edge of the base of the brain.
The structures of the limbic system are responsible for controlling sleep, mood, appetite, sexual behavior. ALL sensory input from the outside and inside
environment enter the brain via
ascending sensory tracts and must pass through the limbic system before
ascending further to the cerebral cortex - - thus our cognitive perceptions and influenced by the limbic system. In lower animals, these structures are more in control of essential behaviors (possibly instinct?).
MIDBRAIN (MESENCEPHALON):
• Red Nucleus and Substantia Nigra:
o Extensions of the extra-pyramidal system for motor control, and produces dopamine.
• Colliculi:
o Visual tracking and head positioning
o This is the primary visual cortex in lower animals (e.g. dog) – so they are better hunters than we are!!
HINDBRAIN (Metencephalon – cerebellum & pons, Myelencephalon – medulla):
1) Metencephalon: cerebellum & pons.
• Cerebellum:
o Two lobes connected by the vermis.
o Maintains balance, fine-tuning of posture. Integrates the afferent/efferent impulses from proprioceptors and other receptors (visual, etc) with cerebral voluntary output.
• Pons:
o Bulging portion below the midbrain and above the medulla.
o Transmits information from spinal cord to cerebellum, controls respiration, contains some cranial nerve nuclei.
o Contains respiratory centers for automatic breathing.
2) Myelencephalon (MEDULLA):
• Also called Medulla Oblongata
• lowest portion of the brainstem & the lowest portion of the Brain.
• Reflex activities controlled here
o heart rate, sneezing, blood pressure, coughing, swallowing, vomiting, automatic breathing
• Cranial nerves:
o CN IX through XII
o the largest and most distributed is the vagus (CN X)
• Pyramidal decussation:
o corticospinal pathways decussate here, at a place that looks like a pyramid, where the name "pyramidal tract" comes from.
• Reticular activating system:
o sleep/awake/arousal states.
• Automatic postural control center:
o Afferent proprioceptive impulses are processed here.
• Automatic breathing:
