14. Neurotrauma

• CNS trauma

  • acute = TBI and traumatic spinal cord injury
  • chronic = degenerative diseases
• the retina is considered part of CNS
• mammalian cns does not regenerate -> causes extreme effects
• cns neurones do not regenerate due to inhibitory environments and the lack of trophic support
• primary damage causes glial response -> sequesters injury site and forms a glial scar

  • also causes secondary damage like inflammation and oedema
• BBB breakdown -> lesion cavity expands due to inflammation -> inflammatory cells interact with reactive glial cells -> reactive astrocytes seal off BBB

  • retains tissue integrity and reduces inflammation response
• scarring is associated with upregulation of inhibitory molecules and ECM deposition
• injured CNS is non-permissive for axonal regeneration and dystrophic neurones develop (abortive attempts at regeneration)
• oligodendrocytes in the CNS do not form a guidance path for sprouting axons and express inhibitory molecules
• astrocytes release factors to promote scar formation and release inhibitory molecules
• myelin debris is not cleared and expresses inhibitory molecules
• CNS axons have some intrinsic capacity (will grow in peripheral environment) but don't due to inhibitory environment

  • lack of neurotrophic factors
  • demyelination
  • glial scar
• stretch injury device = culture tissue in elastic membrane + stretch it, this replicates trauma
• can drop weight onto rats skull to replicate concussion

  • can drop from different heights
• BBB prevents many drugs from entering brain

  • treatments can be given via intravitreal injection (eye)
  • intranasal drugs can also reach brain
• strategies for CNS repair

  • inhibit inhibitory molecules
  • inhibit apoptosis
  • endogenous stem cells - neurogenesis
  • cell therapies, e.g. dental pulp (mesenchymal)