Neural Degeneration and Regeneration

Neural Degeneration

• Transneuronal degeneration occurs when damaged neurons degenerate and spread to linked neurons by synapses.
• Anterograde transneuronal degeneration spreads from damaged neurons to the neurons on which they synapse.
• Retrograde transneuronal degeneration spreads from damaged neurons to the neurons that synapse on them.

Neural Regeneration

• Neural regeneration is the regrowth of damaged neurons.
• In mammals and higher vertebrates, neural regeneration is less successful compared to invertebrates and lower vertebrates.
• In adult mammals, regeneration is virtually nonexistent in the CNS and is limited in the PNS.
• In the mammalian PNS, regrowth from the proximal stump of a damaged nerve usually begins 2-3 days after axonal damage.
• The nature of the injury determines the outcome of regeneration:
  • If original Schwann cell myelin sheaths remain intact, regenerating axons grow through them to their original targets.
  • If the peripheral nerve is severed, regenerating axons may grow into incorrect sheaths and targets.
  • If the cut ends are widely separated, there may be no meaningful regeneration.

CNS-PNS Differences

• Some CNS neurons can regenerate when transplanted to the PNS, but some PNS neurons cannot regenerate when transplanted to the CNS.
• Schwann cells in the PNS promote regeneration by clearing debris and producing neurotrophic factors and cell adhesion molecules.
• Oligodendroglia in the CNS do not clear debris or stimulate regeneration and can inhibit axon growth.

Collateral Sprouting

• When an axon degenerates, adjacent healthy axons grow out and synapse at the vacated sites, a process called collateral sprouting.
• This can occur from axon terminal branches or nodes of Ranvier on adjacent neurons.

Neural Reorganization

• Cortical reorganization occurs following damage in lab animals, with sensory and motor cortex being ideally suited for study.
• Damage can induce reorganization of the primary sensory and motor cortex, which has been studied in two conditions: peripheral nerve damage and cortical damage.
• Studies have shown that cortical areas can reorganize and adapt to new inputs, with the scale of reorganization being greater than previously assumed.

Cortical Reorganization in Humans

• Research has used brain imaging technology to study the cortices of blind individuals, showing an expansion of auditory and somatosensory cortex.
• The findings suggest continuous competition for cortical space by functional circuits.
• There is a functional consequence to this reorganization, with blind individuals demonstrating superior skills on auditory and somatosensory tasks.

Mechanisms of Neural Reorganization

• Two mechanisms of neural reorganization exist:
  • A straightening of existing connections, possibly through release from inhibition.
  • (Other mechanisms not specified)### Recovery of Function After Brain Damage
• Recovery of function after brain damage is poorly understood and difficult to study due to confounding variables.
• Cognitive reserve, equivalent to education and intelligence, plays a role in improvements observed after brain damage.
• Cognitive reserve allows individuals to accomplish tasks in alternative ways, rather than true recovery of lost brain function.
• Educated individuals are less susceptible to the effects of aging-related brain deterioration.

Neuroplasticity and Treatment

• Reducing brain damage by blocking neurodegeneration:
  • Blocking neural degeneration in human patients has shown promise.
  • Apoptosis inhibitor protein has been shown to reduce both neuronal loss and behavioral deficits.
• Promoting recovery from CNS damage by promoting regeneration:
  • Transplanting sections of myelinated peripheral nerve or olfactory ensheathing cells can promote regeneration and recovery.
  • These approaches have shown promise in animal models, but more research is needed.
• Promoting recovery from CNS damage by neurotransplantation:
  • Transplanting fetal tissue or stem cells may help replace damaged neurons or myelin.
  • Positive results have been seen in animal models, but more research is needed.

Neuroplasticity and Rehabilitative Training

• Rehabilitative training can promote recovery from CNS damage:
  • In animal models, training and practice have been shown to reduce the expansion of cortical damage.
  • Constraint-induced therapy, which involves tying down the unaffected arm, has been shown to improve motor function.

Benefits of Cognitive and Physical Exercise

• Cognitive and physical exercise can reduce the risk of neurological disorders:
  • Exercise has been shown to increase dendritic branching, synaptic size, and levels of neurotrophic factors.
  • Enriched environments have been shown to promote neuroplasticity.

Phantom Limbs: Neuroplastic Phenomena

• Phantom limbs are a common phenomenon in amputees:
  • Most amputees experience sensations in the amputated limb, which can be so realistic that they may try to use the limb.
  • Pain can be a significant issue, but may be treated by concentrating on moving the amputated hand.

Alzheimer's Disease

• Alzheimer's disease is a progressive, terminal disorder:
  • It is characterized by neurofibrillary tangles and amyloid plaques.
  • It is thought to be caused by the accumulation of amyloid plaques, which are toxic to neurons.
  • Genetic factors play a significant role in the development of the disease.

Animal Models of Human Neuropsychological Diseases

• Kindling model of epilepsy:
  • Repeated stimulation of the brain can produce a progressive development of convulsions.
  • The kindling phenomenon is a permanent change, and can be produced by distributed stimulations.
• Transgenic mouse models of Alzheimer's disease:
  • Mice engineered to express human genes associated with Alzheimer's disease develop amyloid plaques.
  • A triple transgenic mouse model displays both amyloid plaques and neurofibrillary tangles.
• MPTP model of Parkinson's disease:
  • MPTP, a toxin, can produce cell loss in the substantia nigra, similar to that seen in Parkinson's disease.
  • Deprenyl, a monoamine agonist, has been shown to block the effects of MPTP in animal models.

Neuroplastic Responses to Nervous System Damage

• Neural degeneration:
  • Anterograde degeneration occurs in the distal segment of a cut axon, and progresses quickly.
  • Retrograde degeneration occurs in the proximal segment, and progresses gradually.
  • Early degenerative changes to the cell body suggest that the neuron will ultimately die.
• Neural regeneration:
  • Early regenerative changes indicate that the cell body is involved in a massive synthesis of proteins to replace the degenerated axon.
  • But early regenerative changes do not guarantee the long-term survival of the neuron.