BIOS E-162B Undergraduate Review:

Neuropathophysiology II and III

October 4, 2010

HOT!

HOT!

Afferent pathway (sensory)

The CNS: interneurons, convergence, and divergence

HOT!

HOT!

Via association cortex

Efferent Pathway (motor)MOVE!

SLOW AND STEADY!

REFINE!MOVE!

How movement occurs:The neruomuscular junction

1. Action potential reaches motor neuron terminal 2. Ca2+ enters

3. Vessicles of acetylcholine bind to synaptic cleft

4. Acetylcholine binds to nicotinic receptors on motor end plate

5. Signal to muscle to contract

6. Acetylcholinesterase breaks down acetylcholine, reuptake of acetylcholine into presynaptic neuron

Drugs/Toxins

Curare

• Acts as an antagonist for Ach binding

Botulinum toxin

• Cleaves docking proteins off of the Ach-containing vessicles

Organophosphates

• Inhibit acetylcholinesterase

Strychnine

• Antagonist of the inhibitory neurotransmitter glycine

Tetanus

• Inhibits release of inhibitory transmitter GABA from pre-synaptic nerve terminals in CNS

Diseases

Genetics Injury/ Toxicity

Infection Immune

Myathenia gravis

Parkinson’s

MS

ALS

Guillain-Barre

Myathenia gravis

• B-cells make antibodies that bind to and block Ach nicotinic receptors

• Progressive muscle weakness, usually first at eyes

• Respiratory failure most life-threatening

• Treatment: mechanical ventilation, neostigmine, thymectomy

Parkinson’s Disease

• Loss of dopamine-producing neurons in a region of the basal ganglia

• Side effect of treatment drugs: schizoid behavior

Multiple sclerosis

• Demyelinization of CNS neurons

• Initially present with blurred or double vision

• Muscle weakness, loss of coordination/balance, spasticity, fatigue, paresthesias

• Tysabri appears to be an effective treatment, but with “black box” warning

Amotrophic lateral sclerosis (ALS)

• Loss of upper and lower motor neurons

• Muscle weakness, cramping, atrophy• Respiratory failure, choking• “Charcot ALS” (lower motor neurons first)

vs. “bulbar onset ALS” (upper motor neurons first)

• Riluzole slows progression of ALS, Baclofen relieves muscle spasticity

Guillain-Barre syndrome

• Demyelination of peripheral nerves

• Weakness of respiratory muscles, paresthesia

• Most people recover within one year

Other CNS injuries

Traumatic brain injury

• Damage to nerve axons, leads to loss of axon terminals

• Excitotoxicity and oxidative stress from release of neurotransmitters from damaged cells (esp glutamate)

• Hemorrhages, bruising, pressure from swelling

• Permanent damage, usually

Spinal cord injury

• From trauma, but also from release of neurotrasmitters (esp glutamate)

• Damage depends on site of injury:

SCI II

• Consequences– Loss of temperature control– Brown-Sequard’s syndrome– Pressure wounds– Autonomic dysreflexia

Stroke

• Protection– Circle of Willis– Myogenic autoregulation

• Ischemic (~85% of strokes)– Portion of blood flow to brain is blocked (by

thrombus or embolus)– Ischemic penumbra

• Hemorrhagic (~15% of strokes)– Blood vessel ruptures