NEURO2020 WEEK 12

NEUROPLASTICITY 

• The ability of the brain and nervous system to reorganise itself following damage or environmental change  

• Adult plasticity = reorganisation, not regrowth of neurons 

BRAIN DEVELOPMENT - Ontogenetic Period 

• Early development from birth through childhood and adolescence 

• Newborn brain approx. 350g, adult brain approx. 1,200-1,400g 

• Growth is driven by synapse formation and pruning, myelination, and glial cell development – not merely by adding neurons 

• Extensive flexibility during this phase  

  • Ex. Switch hemisphere of language function 

  • Normal behaviour with just one hemisphere 

CAUSES OF BRAIN DAMAGE - Tumors

• Meningiomas 

  • Grow between layers of the meninges 

  • Encapsulated and benign 

  • Often surgically removed with good outcomes 

• Gliomas 

  • Abnormal glial cells 

  • More serious 

  • Infiltrative types spread throughout brain tissue and must be managed over a lifetime 

• Metastatic tumours 

  • Spread to brain from cancers elsewhere in the body 

CAUSES OF BRAIN DAMAGE - Strokes

• Cerebral haemorrhage 

  • Blood vessel ruptures and blood seeps into the surrounding neural tissue causing damage 

  • Aneurysm – a balloon-like dilation that forms on the wall of an artery where the elasticity is defective  

• Cerebral Ischemia  

  • A blockage in a blood vessel that disrupts blood supply to part of the brain 

  • Thrombosis – a blood clot 

  • Embolism – a blockage movs from a large to small blood vessel where it becomes lodged 

  • Arteriosclerosis – thickening of artery wall, restricting/blocking blood flow 

ISCHEMIA CAUSES..

Glutamate release

STROKE BEFAST ACRONYM

• Balance – loss of balance 

• Eyes – blurred, double vision 

• Face – dropping of one side, asymmetry in a smile 

• Arms – weakness on one side 

• Speech – slurred speech 

• Time – call for help quickly 

CAUSES OF BRAIN DAMAGE - Traumatic brain Injury

• Closed head TBI 

  • Contusions – bruised brain 

  • Subdural hematoma – collection of blood between Dura Mater and Arachnoid Membrane 

• Mild TBI  

  • No physical evidence of injury 

  • Loss of consciousness 

  • Confusion 

• Chronic Traumatic Encephalopathy 

  • Progressive dementia and cerebral scarring from repeated mTBIs 

CAUSES OF BRAIN DAMAGE - Infections and Neurotoxins

• Encephalitis – inflammation in the brain  

  • Bacterial encephalitis – cerebral abscess 

    • Antibiotics can cure abscess but not restore brain function that was damaged 

    • Ex. Bacterial meningitis (30% fatal) 

    • Ex. Syphilis (STI that leads to dementia) 

  • Viral infections 

    • Rabies has an affinity for neural tissue 

    • Fatal if untreated  

• Neurotoxins – chemicals that specifically harm the brain 

  • Mercury 

  • Lead  

  • Endogeneous neurotoxins (cortisol – stress hormone) 

MAD AS A HATTER REFERS TO…

Neurotoxins

PROGRAMMED CELL DEATH - Apoptosis

• Genetically encoded 

• Slow process (1-2 days) 

• Cells shrink, dying parts are packaged into vesicles for disposal (blebbing) 

PROGRAMMED CELL DEATH - Necrosis

• Passive cell death resulting from injury 

• Fast and disordered 

• Neurons swell and break apart 

• The dead parts scatter and harm neighbouring cells 

NEUROLOGICAL DISEASES - Epilepsy

• Focal seizures 

  • one brain region 

  • Epileptic neurons fire synchronously 

  • Characteristic EEG spikes 

• Generalised (tonic-clonic) seizures 

  • Entire brain 

  • Cause loss of consciousness 

  • Violent convulsions, tongue-biting and hypoxia 

• Absence seizures 

  • No convulsions 

  • Loss of consciousness and blank stare 

  • Common in children, usually resolving at puberty 

NEUROLOGICAL DISEASES - Parkinson’s

• Affects 1-2% of people over 65 years  

• Due to degeneration of dopaminergic neurons 

• Treatment  

  • L-Dopa 

  • Deep brain stimulation 

• Full symptoms 

  • Muscular rigidity 

  • Marked tremor at rest 

  • Slowness of movement 

  • Mask-like face  

NEUROLOGICAL DISEASES - multiple sclerosis

• Attacks myelin of axons in the CNS 

• Leaves behind hard scar tissue  

• Treated with L-Dopa 

• Full symptoms 

  • Myelin degrades to point where axon is non-functional 

NEUROLOGICAL DISEASES - alzheimers

1. Preclinical  

   • Brain changes with no outward symptoms 

2. Prodromal 

   • Mild cognitive impairment 

   • Anxiety 

   • Reduced autonomy 

3. Dementia 

   • Progressive memory loss 

   • Attention deficits 

   • Personality changes 

THE KINDLING MODEL OF EPILEPSY

• Repeated mild electric shocks given to rat's amygdala eventually generating convulsive response 

• Is permanent, therefore, a form of neuroplasticity 

• Kindling is similar to epileptogenesis 

THE MPTP MODEL OF PARKINSON’S

• Young drug users presented with classic Parkinson's symptoms 

• MPTP, a neurotoxin in synthetic heroin was the cause  

• Led researchers to use it to help develop treatments  

RESPONSE TO N.S DAMAGE - Degeneration

Axons and dendrites of damaged neuron break down 

RESPONSE TO N.S DAMAGE - Regeneration

• Axons can regrow along remaining Schwann cell sheaths 

RESPONSE TO N.S DAMAGE - Collateral Sprouting

Surviving axons send out new branches that innervate targets left vacant by dead neurons 

RESPONSE TO N.S DAMAGE - Neural reorganisation

• Cortical maps can shift 

• Regions that previously served one function are taken over by adjacent areas 

RESPONSE TO N.S DAMAGE - Release from inhibition

Removing a damaged inhibitory pathway can unmask latent connections in spared tissue 

RECOVERY AFTER TBI

• Recovery after TBI is often in the immediate post-injury period 

  • Due to reduction in brain swelling and dispersal of blood 

• Slow progress seen in later months 

  • Difficult to distinguish physical improvements from newly learned compensatory strategies 

COGNITIVE RESERVE

• The cognitive capacity built up through education and intelligence, enabling the brain to accomplish tasks via alternative neural pathways when primary pathways are damaged.  

• Outcomes after brain injury are generally better for younger patients, those with higher IQ and more education 

COGNITIVE AND PHSYICAL EXERCISE

• Importance of active rehabilitation, not just rest 

• Both cognitive and physical exercise promote neurogenesis and support broader brain health 

PHANTOM LIMBS

• The continued experienced sensations from removed limbs  

• Patients who practised with the mirror box for several weeks reported significant reduction in phantom limb pain 

• Demonstration of how visual feedback can retrain cortical circuits