Brain Damage and Neuroplasticity

Brain Damage and Neuroplasticity

Learning Objectives

  • 10.1 Describe different types of brain tumors and explain the difference between encapsulated and infiltrating brain tumors.

  • 10.2 Describe differences between the two types of stroke: cerebral hemorrhage and cerebral ischemia.

  • 10.3 Describe the two sorts of closed-head traumatic brain injuries (TBIs).

  • 10.4 Describe two different types of infections in the brain.

  • 10.5 Describe three different types of neurotoxins.

  • 10.6 Discuss the symptoms of Down syndrome and what causes this disorder.

  • 10.7 Explain the difference between apoptosis and necrosis.

  • 10.8 Define epilepsy; describe four common types of seizures; and discuss some treatments for epilepsy.

  • 10.9 Describe the symptoms of Parkinson’s disease and some treatments for this disorder.

  • 10.10 Describe the symptoms of Huntington’s disease and explain its genetic basis.

  • 10.11 Describe the symptoms of multiple sclerosis (MS) and its risk factors.

  • 10.12 Describe the symptoms of Alzheimer’s disease and evaluate the amyloid hypothesis.

  • 10.13 Describe the kindling model of epilepsy and explain the ways in which it models human epilepsy.

  • 10.14 Describe the events that led to the discovery of the MPTP model of Parkinson’s disease, and evaluate the utility of this animal model.

  • 10.15 Explain the various types of neural degeneration that ensue following axotomy.

  • 10.16 Compare neural regeneration within the CNS vs. the PNS.

  • 10.17 Describe three examples of cortical reorganization following damage to the brain, and discuss the mechanisms that might underlie such reorganization.

  • 10.18 Describe the concept of “cognitive reserve,” and discuss the potential role of adult neurogenesis in recovery following CNS damage.

  • 10.19 Discuss early work on neurotransplantation for the treatment of CNS damage.

  • 10.20 Discuss the methods and findings of modern research on neurotransplantation.

  • 10.21 Discuss methods of promoting recovery from CNS damage through rehabilitative treatment.

Brain Tumors

  • Tumor Types:

    • Structure:

    • Encapsulated Tumors: Grow within their own membrane.

    • Infiltrating Tumors: Grow diffusely through surrounding tissue.

    • Behavior:

    • Benign Tumors: Do not spread; generally considered non-threatening.

    • Malignant Tumors: Can invade nearby tissues and are considered cancerous.

    • Origination:

    • Gliomas: Tumors that originate in glial cells.

    • Meningiomas: Tumors that grow in the meninges (the protective layers surrounding the brain).

    • Metastatic Tumors: Originate in one organ and spread to another, affecting different parts of the body.

Strokes

  • Definition of Stroke:

    • A cerebrovascular disorder with sudden onset that leads to interruption of blood supply to the brain.

  • Infarct:

    • An area of dead or dying tissue, surrounded by a region known as the penumbra.

  • Causes of Strokes:

    • Cerebral Hemorrhage:

    • Resulting from the bursting of aneurysms, leading to bleeding in the brain.

    • Cerebral Ischemia:

    • Can arise from different phenomena:

      • Thrombosis: A blood clot forms in a blood vessel.

      • Embolism: A blood clot that travels from elsewhere in the body.

      • Arteriosclerosis: Thickening and hardening of the artery walls.

  • Ischemic Brain Damage:

    • Develops over time and varies across different brain regions.

    • Physiological mechanisms leading to neuronal death can include the excessive release of excitatory amino acids like glutamate.

    • The release of glutamate during ischemia can kill postsynaptic cells via NMDA receptor activation.

Traumatic Brain Injuries (TBIs)

  • Contusion:

    • Characterized by injury that includes bleeding without laceration, resulting in a hematoma. This injury often occurs when the brain impacts the skull, potentially causing countercoup injuries.

  • Mild TBI:

    • Results from a blow to the head causing brief disruption of consciousness.

    • No immediate evidence of contusion or structural damage, but effects can long-lastingly influence cognition, motor function, and neurological health.

    • Chronic Traumatic Encephalopathy (CTE):

    • A condition found in individuals who have suffered multiple mild TBIs over time.

Infections of the Brain

  • Encephalitis:

    • A brain infection caused by various agents.

    • Causative Agents:

    • Bacterial: Can cause conditions like meningitis and brain abscesses, treated using antibiotics.

    • Viral: Certain viruses preferentially attack the CNS (e.g., rabies) and may be implicated in other disorders.

Neurotoxins

  • Types of Neurotoxins:

    • Heavy Metals: Can lead to toxic psychosis.

    • Pharmaceuticals: Some drugs used to treat neurological or psychiatric disorders can produce side effects like tardive dyskinesia.

    • Endogenous Agents: May include antibodies against components of the CNS.

Genetic Factors

  • Can stem from accidents during cell division.

  • Down Syndrome:

    • Caused by the presence of an extra 21 chromosome.

  • Increased risks can be associated with specific abnormal recessive or dominant genes affecting multiple loci on chromosomes.

Programmed Cell Death

  • Apoptosis:

    • The process of programmed cell death that occurs in dysfunctional cells and is generally seen as adaptive.

    • Early impacts on the nucleus are observed.

  • Necrosis:

    • Refers to passive neuron death due to injury, leading to inflammation, with late impacts on the nucleus.

Epilepsy

  • Characteristics:

    • Seizures occur spontaneously and can be diagnosed through signs like clonus/tonus, balance loss, and loss of consciousness.

    • Some seizures might involve changes in thought, mood, or behaviour without convulsions.

    • Classes of Seizures:

    • Focal Seizures:

      • Simple Seizures: Mostly sensory or motor, localized.

      • Complex Seizures: Often observed in temporal lobes, involve automated behaviour and can lead to longer motor sequences.

    • Generalized Seizures: Involve more widespread brain impact.

      • Tonic-Clonic Seizures and Absence Seizures: More common in children; absence seizures are characterized by disrupted consciousness without convulsions.

Treatments for Epilepsy

  • Options Include:

    • Anticonvulsive medications, Vagus nerve stimulation, Transcranial magnetic stimulation, Ketogenic diet, and Surgery.

Parkinson’s Disease

  • Characteristics:

    • Affects 1–2% of the population over age 65 and is slightly more prevalent in males.

    • Symptoms:

    • Tremor or stiffness in fingers, tremors at rest, muscular rigidity, slowness of movement, and a masklike facial appearance.

  • Causes:

    • Results from the degeneration of dopamine neurons in the substantia nigra.

  • Treatments:

    • Include L-dopa administration and deep brain stimulation.

Huntington’s Disease

  • Characteristics:

    • This motor disorder is inherited and often leads to dementia.

    • Symptoms:

    • Complex, jerky movements that typically do not manifest until individuals are between 40 to 50 years of age.

    • Cause:

    • Linked to a single mutated dominant gene known as the Huntingtin gene.

Multiple Sclerosis (MS)

  • Characteristics:

    • Involves degeneration of myelin.

    • Symptoms:

    • Ataxia, weakness, numbness, tremors, and poor vision.

  • Causes:

    • Potentially linked to a faulty immune system.

  • Epidemiological Studies:

    • Show a higher incidence in monozygotic twins (35% concordance) compared to dizygotic twins (6%); more prevalent in females, among Caucasians, and populations residing in colder climates.

Alzheimer’s Disease

  • Symptoms:

    • Include memory decline, emotional instability, impairment of speech function, complete dementia, and loss of ability to perform basic tasks like swallowing.

    • Terminal Effects: Ultimately leads to extensive cognitive decline.

  • Diagnosis:

    • Confirmed at autopsy by observing amyloid plaques, neurofibrillary tangles, and loss of cells in critical areas such as the hippocampus, amygdala, and entorhinal cortex.

Treatments for Alzheimer’s Disease

  • Aim to increase acetylcholine function, reduce amyloid plaques, and target relationships between Down syndrome and Alzheimer’s in treatment regimens.

  • Efforts also directed toward addressing misfolded protein hypotheses.

Kindling Model of Epilepsy

  • Procedure:

    • Electrical brain stimulation applied once daily leading to eventual elicited convulsions; over time, generalized convulsions develop.

    • Convulsions mimic human epilepsy and can be induced through chronic administration of convulsive drugs.

    • Physiological changes observed may reflect mechanisms responsible for developing epilepsy.

MPTP Model of Parkinson’s Disease

  • Model Development:

    • Originated from a human accident in 1982 when young individuals exhibited Parkinson’s-like symptoms after exposure to the neurotoxin MPTP.

  • Utility of the Model:

    • Particularly effective in primate studies, where loss of neurons in the substantia nigra occurs, leading to dopamine reduction and similar symptoms to those present in humans.

Neural Degeneration

  • Types of Degeneration:

    • Anterograde Degeneration: Occurs distal to the injury site.

    • Retrograde Degeneration: Occurs proximal to the injury site.

  • Transneuronal Degeneration: Involves degeneration spread through neural circuits; can be either anterograde or retrograde.

Neural Regeneration

  • Regrowth Possibilities:

    • More readily observed in invertebrates compared to higher vertebrates; some mammalian regeneration occurs in the PNS but is nearly nonexistent in the CNS.

  • PNS Regeneration:

    • Begins from proximal stump with regrowth through an intact myelin sheath, critical for successful neuronal regrowth; Schwann cells play vital roles through trophic factors and cell adhesion molecules (CAM).

  • CNS Regeneration:

    • Some collateral sprouting may occur following injury.

Neural Reorganization

  • Research Findings:

    • Kaas et al. observed that retinal lesions lead to instantaneous reorganization of visual fields.

    • Sanes et al.’s work showed that transecting motor neurons reorganized the motor cortex within weeks.

    • Blind individuals demonstrated significant overrepresentation of auditory and somatosensory inputs in the brain due to neural plasticity.

  • Types of Changes:

    • Can result from the release of previously unused connections from inhibition, collateral sprouting, or adjustments to dendritic trees, including neurogenesis.

Recovery of Function After CNS Damage

  • Challenges of Study:

    • Determining if recovery arises from real functions regained or if it results from compensatory behavioral strategies.

  • Cognitive Reserve:

    • Refers to the brain's capacity to recover cognitive function, often through adopting alternative strategies for problem-solving.

Neurotransplantation as a Treatment for CNS Damage

  • Early Research Findings:

    • Stimulated by successes in animal models like MPTP; trials included transplanted dopamine cells from the adrenal medulla in patients with Parkinson’s disease and Schwann cell transplants to encourage CNS regeneration.

  • Modern Research:

    • Stem cells identified as pluripotent, capable of stimulating remyelination, releasing neurotrophic factors, and differentiating into glial cells.

Promoting Recovery from CNS Damage through Rehabilitative Training

  • Benefits Include:

    • Reduced cell loss after ischemic stroke, improved recovery following spinal cord injury, and enhanced outcomes from enriched environments resulting in greater dendritic branching, increased dendritic spines, neurogenesis, and elevated levels of neurotrophic factors.