Neuron

Neuron

Multipolar Neuron

Synapse

Best Known Neurotransmitters

n Acetylcholine (ACh)

n Norepinephrine (NE)

n Dopamine DA)

n Serotonin or 5-Hydroxytryptamine (5HT)

n GABA

n Endorphin

Acetylcholine (ACh)

n neurons using ACh are known as “cholinergic neurons”. Examples:

n motor neurons

n parasympathetic neurons

n many CNS neurons (in cortex, basal ganglia, hippocampus, brainstem)

n acetylcholinesterase breaks down ACh

Norepinephrine (NE)

n aka “noradrenaline”

n transmitter of symnpathetic synapses to organs and glands

n also found in many CNS neurons (RF, hypothalamus)

n action terminated by reuptake

n closely related to DA (“catecholamines”) and both related to 5HT (monoamines)

Dopamine(DA)

n primarily known as a CNS transmitter

n transmitter in basal ganglia, limbic system & frontal cortex & parts of hypothalamus that control pituitary

n action terminated by reuptake

Serotonin (5HT)

n primarily known as CNS transmitter

n found in neurons of brainstem associated with sleep & pain suppression, & in limbic system

n action terminated by reuptake

GABA

n best known inhibitory transmitter

n widely distributed in CNS

n seems necessary to keep neuron activity “in check”

Neuromuscular Junction

Myasthenia Gravis: A Neuromuscular Disease

n abnormal muscle fatiguibility & weakness

n progressive, usually affects muscles of head 1st

n autoimmune disease attacking ACh receptors on muscles

Patient Asked to Look Up

Ptosis (drooping of eyelid)

n Maybe Sleepy had MG

MG Tests

n Intravenous administration of Tensilon (edrophonium), a short-acting anti-cholinesterse, usually produces brief improvement

n Nerve conduction studies show normal conduction; electromyogram shows normal muscle response which decreases with each response

n Chest xray may show thymoma

MG Treatments

n Decrease the attack by the immune system:

• immunosuppressant drugs

• thymectomy

• plasma exchange to remove antibodies

n Increase ACh levels with an anti-cholinesterase drug (prevents normal breakdown of ACh, prolonging it ability to stimulate remaining ACh receptors)

Botulinum Toxin

n Toxin produced by bacteria Clostridium botulinum or its spores, incredibly potent, easily absorbed from GI tract, and then distributed by blood everywhere except CNS

n Intereferes with the release of ACh, causing paralysis & autonomic effects

n Selective injections of botulinum toxin now used to treat excess muscle contraction (spasticity)

Action of Botulinum Toxin

Black Widow Spider Venom

Neurons and Glia

Glial Cells (“supporting cells”)

n 5-10X more numerous than neurons

n make up about half of brain weight

n several distinct types

n growing evidence of multiple roles that glia play

Astrocytes (most common)

n separate synapses

n form a “limiting membrane” on outside of CNS

n surround CNS capillaries adding to blood-brain barrier

n transfer materials to & from neurons

n produce growth factors

n clean up excitatory transmitter glutamate

n may even communicate?

n can multiply to form scar tissue or tumors

Astroglia or Astrocyte

Oligodendrocytes

n the other large glial type (“macroglia”)

n form myelin sheaths on CNS neurons

n form thin coat on unmyelinated ones

n produce nerve growth factor

n Schwann cell is the PNS counterpart

Myelin Sheaths

Cross-section of Nerve

Axons Within Nerve

Microglia

n small glia which are mobile phagocytes

n Recent evidence suggests they play a key role in neurodegenerative diseases - “activated” microglia may attack neurons in AIDS, Alzheimer’s, MS, etc.

n contribute to scar tissue formation

Ependymal Cells

n line the ventricles/canals

n participate in CSF production

n have cilia to help circulate CSF

n may transport materials between CSF & neurons

Glia Clinical Notes

n 60% of brain tumors are gliomas

n multiplying of glia to form scar tissue (“gliosis”) can irritate nearby neurons: important cause of focal epilepsies

Multiple Sclerosis: Another Autoimmune Disease

n Immune system attacks miscellaneous myelin sheaths in CNS, causing demyelination in 250,000 in US (2/3 are women)

n Where myelin is lost, hard plaques of scar tissue (glia & immune cells) form

n Symptoms depend on which neurons lose myelin but always multiple symptoms (clinically diagnosed)

n Periodic attacks (days) & then remissions (months) which progress

Loss of White Matter in MS

Demyelination Seen in MRI

What Causes MS?

n More common in northern climates

n For some reason B-cells attack oligodendrocytes, T-cells attack certain myelin proteins that resemble a virus.

n Illness activating immune system can aggravate the disease

n Less common in Blacks, Asians, Native Americans and shows some tendency to run in families (role of genetics). Identical twins have 30% concordance.

MS Treatment Approaches

n Avoid stress & illness; treat the specific symptoms

n Steroids & other immunosuppressant drugs to shorten attacks

n New meds: beta-interferon, methotrexate

Consider this:

n You’ve recently had the flu or some other infection (60%), or you’ve had a vaccination. You notice some tingling & numbness in your feet & your legs seem to be getting weaker (60% can’t walk). Over a period of hours (or up to 2 weeks) the weakness & loss of ability to move moves up your body. If it gets high enough you may not be able to breathe (20-30%) swallow, or speak & may have bilateral facial paralysis. 5% die

Guillain-Barre Syndrome

n Rapid ascending, usually symmetrical PNS demyelination

n Loss of motor function most obvious; some numbness & back pain possible

n Can be a medical emergency- 25% need artificial respiration

n Probably a temporary autoimmune disorder; majority have recently had an infection or vaccination

n Some begin recovery within weeks, others months. 70-80% full recovery

GBS

Brain Tumors or Neoplasms

n Usually due to abnormal growth of tissues /cells other than neurons

• ~15-20% Meningiomas - benign, encapsulated growth of meninges

• ~60% Gliomas - infiltating, usually malignant multiplication of glial cells

– Most common – astrocytoma

– Most dangerous – glioblastoma multiforme

– Acoustic Schwannoma/neuroma - covering on 8th cranial nerve grows

• ~10-30% metastatic tumors (originate outside the brain, e.g. in lungs, breasts)

Brain Tumors continued

n Most tumors occurring in adulthood are “supratentorial” (in cerebral hemispheres)

n Most tumors in children are “infratentorial” (below tentorium, in brainstem). The single most common is a medulloblastoma.

n Tumor problems: compression of brain area, infiltration, increased ICP, sometimes may impair CSF flow or endocrine controls.

Meningitis

n Can be caused by bacteria, virus, fungus, or reaction to medications

n Headache, fever, irritability, stiff neck, photophobia, nausea, possible seizures or altered cognition

n Bacterial meningitis can progress very rapidly so is a medical emergency

n Viral meningitis is generally less serious

n Inflammation/swelling can lead to lasting deficits in 20-30% (impaired hearing, retardation, epilepsy)

Tests

n Lumbar puncture to identify infection

n Kernig’s sign

n Brudzinki’s sign

Some Other CNS Infections

n Viral

• May be pantropic (general infections of many tissues like mumps or herpes) or neurotropic (specific affinity for nerves).

• Example: viral encephalitis – many varieties (St. Louis, Equine, HIV) – virus spreads to brain itself with high risk of mortality or disability

• Common forms spread from animals to humans by mosquitos

Rabies – a neurotropic infection

n Virus is picked up by nerve endings at the site of the bite & slowly(2 weeks-6 months) travels to CNS via retrograde transport. If the virus reaches the CNS before vaccination it is invariably fatal.

n Symptoms may appear in 2 forms: “furious rabies” - hyperexcitable, irritable, muscle pain and spasms, may viciously bite at anything, or “dumb rabies” - lethargy progessing to paralysis & coma

Creutzfeldt-Jakob Disease

n Progressive dementia and cerebellar ataxia

n In past most cases caused by exposure to tissue (cornea or dura transplants, human growth hormone injections, contamination from previous brain surgery on infected patient). A few (5-10%) cases are familial

n Long incubation period

n Caused by tiny abnormal proteins (prions) which are very resistant to inactivation

Bovine Spongiform Encephalopathy (BSE)

n Related animal diseases transmitted even through eating feed containing tissue from infected (“mad cow disease”)

n 1996 – evidence that BSE could cause a type of CJD in humans

n 1/2001 – FDA recommends banning blood donations from those who lived in BSEcountries

n BSE identified in these countries

Fungal (most often Candida albicans)

n Usually in immune-compromised individuals

Infections continued

n Parasitic Bacterial Infections

• Syphilis

• Lyme Disease (from ticks)- untreated can cause arthritis and neurological problems like

• Bell's palsy - facial muscle droop

• meningitis

• encephalitis

• tingling of extremities

• trouble with concentration *

• memory loss *

• extreme fatigue *

Tick Bite

Bull’s Eye Rash