1. BIOS E-162B Undergraduate Review: Neuropathophysiology II and III October 4, 2010

2. HOT! Afferent pathway (sensory)

3. The CNS: interneurons, convergence, and divergence HOT! Via association cortex

4. Efferent Pathway (motor) MOVE! SLOW AND STEADY! REFINE! MOVE!

5. 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

6. Drugs/Toxins

7. Curare Acts as an antagonist for Ach binding

8. Botulinum toxin Cleaves docking proteins off of the Ach- containing vessicles

9. Organophosphates Inhibit acetylcholinesterase

10. Strychnine Antagonist of the inhibitory neurotransmitter glycine

11. Tetanus Inhibits release of inhibitory transmitter GABA from pre-synaptic nerve terminals in CNS

12. Diseases GeneticsInjury/ Toxicity InfectionImmune Myathenia gravis Parkinson’s MS ALS Guillain-Barre

13. 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

14. Parkinson’s Disease Loss of dopamine-producing neurons in a region of the basal ganglia Side effect of treatment drugs: schizoid behavior

15. 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

16. 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

17. Guillain-Barre syndrome Demyelination of peripheral nerves Weakness of respiratory muscles, paresthesia Most people recover within one year

18. Other CNS injuries

19. 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

20. Spinal cord injury From trauma, but also from release of neurotrasmitters (esp glutamate) Damage depends on site of injury:

21. SCI II Consequences –Loss of temperature control –Brown-Sequard’s syndrome –Pressure wounds –Autonomic dysreflexia

22. 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