1 Questions: ① What types of nervous system regeneration exist? ② How do PNS neurons regenerate? ③ How do CNS neurons regenerate? ④ What are features of spinal cord damage? ⑤ What are features of a stroke in the brain? An ancient Egyptian papyrus acknowledges the difficulties of repairing brain and spinal cord damage “When you examine a man with a dislocation of a vertebra of his neck, and you find him unable to move his arms, and his legs…. Then you have to say: a disease one cannot treat” Question 1: Three types of nervous system repair or regeneration (Part 1) I: regrowth of axons. Mainly PNS Growth cone: change in speed and shape Cell adhesion molecules (CAMS)2 Question 1: Three types of nervous system repair or regeneration (Part 2) II: restoration of damaged nerve cells in CNS Some connections established; glial cells form ‘scar tissue’ glial cell proliferation Axons/dendrites degenerate Question 1: Three types of nervous system repair or regeneration (Part 3) III: genesis of new neurons Shown in olfactory bulb and hippocampus; not the cortex Question 2 • “On April 25, 1903, the radial (ramus cutaneous radialis) and external cutaneous nerves were divided (cut) in the neighborhood of my elbow, and after small portions had been excised, the ends were united with silk sutures. Before the operation the sensory condition of the arm and back of the hand had been minutely examined and the distances at which two points of the compass could be discriminated had been everywhere measured.” (Ch. 25, page 638) v Head, Rivers, and Sherren, 1905, Brain 28: 99-115. Question 2: Henry Head’s peripheral nerve regeneration experiment Recovery: 1. General sense of touch, pressure (not localized) ± 6 wks 2. Temperature, 2-point discrimination, light touch. ± 2 years (but less restoration)3 Question 2: Regeneration in peripheral nerves Schwann Cells: promote axon growth and synapse formation Question 2: Molecular and cellular responses that promote peripheral nerve regeneration Regeneration of synapses: - Visual system - Neuromuscular junction Peripheral nerve sheaths and Schwann cells facilitate growth of damaged axons Peripheral nerve: back/leg4 Reinnveration of muscles following peripheral motor nerve damage (Part 1) Original synaptic sides remain intact for weeks: Schwann cells, Ach receptors Reinnveration of muscles following peripheral motor nerve damage (Part 2) Question 3 • Damage to CNS: § Trauma § Hypoxia (stroke, cardiac arrest) § Neurodegenerative disease • All these lead to programmed cell death (apoptosis) • Autoimmune system regulated glial cells (macrophages) contribute to degeneration and regeneration Question 3: The reaction of the three major classes of CNS glia to local tissue damage Brain myelin, produced by oligodendrocites, inhibits axon regrowth5 Question 3: Cellular response to injury in the central nervous system Question 4: spinal cord damage Spinal Cord • Spinal cord retraining based on current knowledge of central pattern generators • Injecting L-Dopa in spinal cord: alternating flexion/extension movements (cat/mouse)6 Spinal cord damage • Plegia: motor inhibition caudal to level of injury § Quadriplegia: all 4 extremities § Paraplegia: legs § Hemiplegia: one side (stroke) • Symptoms: § Flaccid: total loss of muscle activity § Spastic: increase in muscle tone Spinal cord damage • Spinal cord injury § Large sympathetic stimulation (minutes); Swelling ->loss of blood pressure (restricted blood flow = ‘Ischaemia’) and activation of nerves; § Spinal cord shock (weeks); even undamaged areas become disabled (release toxic chemicals; ‘2nd cascade’). § Inflammatory immune response causes more damage; use methylprednisolone (steroids) § Spasticity and hyperreflexia Damages both lower (innervate muscle fibers) and upper motor neurons (originate in brainstem and motor cortex: Question 5: Stroke • Stroke: damage to brain -cortex § Thrombotic – blood flow reduction due to atherosclerosis (50%) § Embolic – blockage due to embolus (small object in bloodstream) (30%) § Hemorrhagic – rupture of cerebral blood vessel (20%) • http://www.sciencedaily.com/videos/2008/1207-retrain_your_brain_after_stroke.htm • Pharmacological strategies to minimize neuronal injury after stroke due to inflammation. § Example: excitoxicity – glutamate acummulates in synapse -> excessive stimulation of glutamate receptors -> excites neurons to death.7 Spasticity and muscle tone • Muscle tone: resting level of tension in muscle. Tone depends on: § Resting level of alpha motor neurons (and Ia spindle afferents) § Structural aspects (contractures) • Spasticity § Increased tone § Hyperactive reflexes § Clonus (rhythmic contractions due to stretching and unloading of spindle) Questions: ① What types of nervous system regeneration exist? ② How do PNS neurons regenerate? ③ How do CNS neurons regenerate? ④ What are features of spinal cord damage? ⑤ What are features of a stroke in the