Lecture 4 Study Questions Flashcards
What are the similarities and differences in regenerative capacity of injured peripheral axons vs. injured central axons?
Both injured peripheral and central axons have the same capacity to regenerate as they both have growth cones.
Central axons have less regenerative success due to the presence of Nogo. Nogo is an axonal extension inhibitor expressed by oligodendrocytes. Nogo’s presence results in the collapse of dorsal root ganglion growth cones.
How did Ramón y Cajal prove that cut central axons can indeed regenerate if a suitably nourishing environment is provided?
Ramon y Cajal took transected peripheral nerves and implanted them into the brain. Central axons were able to grow into the implanted pieces of sciatic nerve. Without the peripheral nerve implant, central axons would sprout but not elongate. He proved that within peripheral nerves there existed a growth promoting substrate.
How did Albert Aguayo follow-up on this work in the 1980’s and what did his group conclusively prove?
Albert Aguayo demonstrated that spinal cord axons could regenerate up to the central nervous system border with a sciatic nerve graft. This study proved that central nervous system regeneration is possible in adult mammals.
Describe grafting strategies for spinal cord injury repair that continue to be studied.
The Miami Project to Cure Paralysis is currently studying the safety and efficacy of autologous human Schwann cell augmentation in peripheral nerve repair. This involves the extraction, culture, purification, and reimplantation of Schwann cells into patients with SCI. Note that the Schwann cells are taken from the participant and implanted back into the same participant.
Describe factors that assist or limit CNS regeneration. What is Nogo and where is it expressed?
Nogo is an axonal growth inhibitor that collapses dorsal root ganglion growth cones. It is expressed in oligodendrocytes which are found within the central nervous system. This is a factor that limits central nervous system regeneration.
Findings suggest that blocking NOGO may facilitate nerve regeneration as it will hide the inhibitor from growing nerve fibres.
Describe reasons why central axons may regenerate but fail to successfully reestablish connections.
Central axons fail to reestablish connections as they are stabilized when they enter the CNS at the dorsal root entry zone. The axon tips and adjacent shafts are stalled. This is possibly due to the production of NOGO from oligodendrocytes in CNS myelin. NOGO is an axonal inhibitor expressed by oligodendrocytes that collapses dorsal root ganglion growth cones.
Describe the possibilities after optic nerve injury
Optic nerve regeneration can often go awry as cellular and molecular mechanisms disturb axonal guidance. Within the eye and optic nerve, bulbous axonal stump, intraocular axonal growth, axonal branching and axonal u turns can be observed after injury. Within the optic chiasm, misrouting to the contralateral optic nerve, misrouting to the ventral hypothalamus, and abnormal ipsilateral growth can occur. Rarely, normal contralateral crossing occurs.
To what extent does neurogenesis occur in the adult mammalian brain, and where?
Neurogenesis occurs in the subventricular zone and subgranular zone. The subventricular zone lines the lateral ventricles and new cells migrate to the olfactory bulb via the rostral migratory stream. The subgranular zone is located in the dentate gyrus of the hippocampus. Many of the newborn cells die shortly after they are born, but some become functionally integrated into surrounding brain tissue.
