PSYC 170  - Summer 2013 - Professor Claffey

Notes: Damage


__________ - localized damage, typically associated with a change in function/abilities
    sometimes a literal hole - neurons die, area fills with cerebrospinal fluid

Cerebrovascular Disorders

problems with blood flow to the brain

    cardiopulmonary failures (heart attacks), near-drowning, strokes, carbon monoxide
    generally 4-6 minute can result in permanent damage

sleep apnea can reduce blood oxygenation from 95% to ~50%

    swelling of the ventricles due to blockage of cerebrospinal fluid
    swelling can disrupt blood flow and distort tissue


U.S. Statistics

routes of harm:
   - anoxia/hypoxia to affected tissue
   - intracranial pressure and distorted tissue
   - compromise of blood-brain-barrier   

  ______________ - the area of dead/damaged tissue

cerebral ____________________
    rupture of blood vessels
    balloon like expanse in an artery:  ____________________

cerebral ____________________
    disruption of blood flow   
    thrombosis - a plug or clot that develops in place
    embolism - a plug or clot that breaks free, travels through blood stream, lodges elsewhere
    arteriosclerosis - narrowing of arteries by fatty plaques

ischemic cascade ischemic cascade
    disruption of oxygen delivery causes energy crisis & failure to
    maintain cell homeostasis
 fail to: ______________________
     internal build up of Na+, permanent depolarization,
     glutamate release

 fail to: clean up ____________________
     causes over stimulation of post-synaptic neurons
     influx and toxic buildup of ________ in post-synaptic neuron
     over-stimulation of next post-synaptic neuron, cycle repeats

 cell metabolism is catastrophically altered by _______
    overexcited enzymes, breakdown of mitochondria and membrane

damage takes days to develop
    some areas more sensitive than others: hippocampus
stroke MR
a) 4 hours after symptoms, b) 1 week after symptoms
Source: Weis-Müller et al, 2007

    ________ imaging - detect round, clean edge lesions of uniform density, noninvasive

    _____________ - inject contrast dye into venous/artery system, more detailed but invasive

Intracranial Tumors

morbid, uncontrolled growth of tissue
brain tumors make up 5% of all cancers
most common in early and middle adulthood
because CNS neurons do not typical undergo mitosis (reproduce),
   tumors usually do not originate from neurons

_____________ (from "glial" cells)
    infiltrative tumors
    difficult surgery, unlikely to remove completely, often reoccurring
    40-50% of brain tumors

Benign (left) vs malignant (right) tumors
brain tumors
____________________ (originating in the meninges)
    usually benign, wrapped in a membrane
   easier to surgically remove
    slow growing, can become quite large
    cause problems by displacing tissue,
        but brain can sometimes adapt for years
    about 15-20% of brain tumors

    originating from elsewhere in the body
    typically closer to cortical surface but can be anywhere
    difficulty surgery, poor prognosis because already spreading
    15% of brain tumors

pituitary tumors
    pituitary gland is a major interface between nervous and endocrine system
    can result in excessive growth hormones, resulting in giantism
    15% of brain tumors

symptoms: headaches, nausea, seizures, disruption of cognitive function
has effects by disrupting neural tissue, vascular compression, endocrine interference
typically diagnosed using CT or MR imaging

Traumatic Brain Injury (TBI)

U.S. Statistics
    2 million per year
    4th leading cause of death (1st in persons aged 1-44 years)
    50% of trauma deaths are secondary to TBI (35% of these gunshot wounds)
    92% mortality rate for gunshot wound
    Source: Vinas & Pilitis, 2006

________ head injury
    penetration of the skull
    death typically caused by disruption of blood flow (ischemic cascade)

_________ head injury
    impact or sudden acceleration, but skull was not fractured
    adolescents & young adults: accidents, defuse damage
    65 and older: falls, focal damage

Closed Head Injuries

    a "mild" TBI
    altered consciousness for 2-30 minutes
    no evidence of vascular damage
    symptoms: cognitive, somatic (dizzy, nausea), emotional
    not considered a medical event until ~1980s
    increasing awareness of potential for long term damage, especially with repetition


closed head injury
____________________ of axons
    damage is not immediate
    subsequent neuron death
    difficult to detect with imaging
    over long term, shows up as decreased volume
       (enlarged ventricles)

______ - at site of impact
    countrecoup - opposite of impact, due to rebound
    most common in frontal and temporal lobes


____________________ - damage to circulatory system
    produces a hematoma (bruise)
    even trivial tears can cause problems weeks later

    swelling of tissue

   caused by hematoma or edema
   downward compression of brain
   pressure on brainstem, cranial nerve, cerebral arteries


loss or altered consciousness
    Glasgow Coma Scale - assess eye opening, motor response, verbal response
        low scores 6 hours after injury indicates 35-50% chance of death within 6 months

post-traumatic anterograde amnesia
    difficulties forming new memories
    lasting longer than 3 weeks indicates poor prognosis

difficulties with divided attention, behavioral control, planning, abstract planning

Sports Related Injuries

football, boxing, rugby, horseback riding

dementia pugilistica
    tremors, difficulty speaking, abnormal reflexes
    related to the number of matches (Mortimer & Pirozzolo, 1985)

subtle but long-term cognitive differences
    number of concussions (ranging from 0-7) in amateur soccer players was inversely correlated with
        performance on planning and memory tests
        Matser et al, 1999
    rugby players with single mild head injury (<20 minutes of altered consciousness, amnesia < 24 hours)
        changes in visual attention task still present 1 year later
        Cremona-Meteyard & Geffen, 1994



_____________________ - inflammation of brain due to the invasion of a microorganism
    bacterial - syphilis, Lyme disease, malaria
    viral - rabies, mumps, herpes encephalitis
    cause deficits by interfering with cell function and producing an inflammatory response


Drugs: alcohol, marijuana, LSD, MDMA
    Difficult to disambiguate neurological effect of the drug from:
        cognitive deficits associated with a person's increased likelihood to take drugs
        cognitive deficits associated with risky or neglectful drug-related behaviors

Lead, organic solvents, pesticides (organophosphates)
    Some improvement after leaving harmful environment, but usually lasting effects

Neuron damage & regeneration

____________________ - the ability of neuron configurations, and therefore the brain, to change with time and recover
    critical to development, learning and recovery


    programmed cell death
    slow, orderly disintegration of cells, no inflammation, doesn't disturb neighboring cells
    (Full review: Apoptosis in neurodegenerative disorders, Nature Reviews Mol Cell Bio, Mattson 2000)

    sudden, disorderly cell death
    causes inflammation, disrupts neighboring cells

transneuronal degeneration _____________________ degeneration
    damage between cut and synaptic terminals
    this is the distal portion of the neuron

_____________________ degeneration
    damage between cut and cell body
    this is the proximal portion of the neuron

_____________________ degeneration
    when a neuron dies, other neurons that are
        post-synaptic, or
    may also die


Unsuccessful in mature mammals and higher vertebrates
    CNS - virtually non-existent
    PNS - unlikely but possible

neuronal regeneration Regeneration in PNS
    requires original _________________________ to be intact
        neurotropic factors - chemicals that encourage tissue growth
        CAMs - cell adhesion molecules, provide guidance

    new growth may connect to incorrect targets

It is not the neurons themselves, but the environment
    CNS neurons transplanted to PNS will regenerate
    PNS neurons transplanted to CNS will not regenerate


Example 1: Reorganization in V1 following retinal lesions
    In adult monkeys, remapping can occur within hours (Botelho et al, 2012)

rewiring the auditory cortex

Example 2: Rewiring neurons from the eye to the auditory cortex
    In the developing ferret, input to MGN (auditory) is removed
    MGN then "attracts" input from retinal ganglion cells
    Visual stimuli produce activity in the auditory cortex

Source: Sur & Leamey, Nature Reviews Neuroscience, 2001

Example 3: In newly blinded individuals, auditory and somatosensory input is processed in formerly visual areas

Example 4: Phantom limb
    somatosensory cortex that previously received input from amputated arm begins responding to neighboring input
    Example: touching a patient's cheek can feel like touching the amputated arm


Treatment & Recovery

____________________ - return of original function in a damaged area
    Example: after a stroke affecting the hand motor area, that tissue recovers and hand function returns

____________________ - performing a function by newly learned methods using non-damaged areas
    Example: after a stroke affecting the hand motor area, neighboring tissue learns to operate the hand

1. Reducing degeneration

        apoptosis inhibition
        nerve growth factors
        estrogen (Review: Brann et al, 2007)
            females have better incidence/outcomes in neurological pathologies
            administration of estrogen improves post-stroke outcomes in rodents

2. Promoting regeneration

        can be induced in CNS neurons by Schwann cells (Xu et al, 2004)
        physical activity promotes adult neurogenesis in rodent hippocampus

3. Transplant

        fetal substantia nigra cells for treating monkeys with Parkinson's disease-like symptoms
            limited success with humans
        embryonic stem cells in rat damaged spinal cord improved mobility

4. Rehabilitative training

        for hands, restrict the functioning limb to maximize use of impaired hand
        for spinal cord injuries, facilitated walking


Copyright 2012-2013 - Michael Claffey