November 3rd

1. November 3rd • Time is short today • Hand in Brain Scan Organizer please • Go over Brain lab an Organizer in 6 minutes! • Lecture on Brain Disorders • Case Study on Phineas Cage • In class video and questions to complete on this study • HW: MC practice and Blog Post! Please make sure you are up to date on readings • Next Class 3C (Genetics) /Review • Test: November 14th

2. Brain Damage 1st case widely cited in medicine to infer that brain function can alter personality Phineas P. Gage (July , 1823 – May 21, 1860)

3. ~1850 Pattern of injury is very localized -blood vessels spared - only frontal cortex damaged - loss of 1 eye Consciousness regained in days - personality/behavior dramatically altered - child-like, profane, disinhibited, inappropriate, inability to control anger and other emotions. Referred to today as classic “hypofrontality” -common with traumatic injury to the frontal lobes Until 2008, commonly thought that he demonstrated these symptoms until his death, 12 years later. But this was not true… “Social Recovery”

4. Brain Damage • Traumatic brain injury • Strokes • Alzheimer’s Disease • Parkinson’s Disease Other neurological disorders discussed in the book will NOT be subject to test questions

5. Traumatic Brain Injury FACTS: 50,000 die; 235,000 are hospitalized; and 1.1 million are treated and released from an emergency department. What causes TBI? Falls (28%) Motor vehicle-traffic crashes (20%) Struck by/against (19%) Assaults (11%) Who is at highest risk for TBI? Males are about 1.5 times as likely as females to sustain a TBI.1 The two age groups at highest risk for TBI are 0 to 4 year olds and 15 to 19 year olds

6. Types of Traumatic Brain Injury “Closed Head Injury” Concussion. Concussions are the most common type of TBI. A concussion is damage to nerves or blood vessels in the brain often caused by an impact to the head. Contusions. A contusion is a bruise or bleeding on the brain that can be caused by an impact. Diffuse Axonal Injury. This is tearing of nerve tissue or blood vessels when the brain is jostled in the skull. It can result from shaking (for instance, shaken baby syndrome) or whiplash Coup-countrecoup Injury. impact not only injures the site of impact, but causes the brain to impact with the skull, causing injury to the opposite side of the brain. Symptoms: acute: confusion, visual disturbance, unconsciousness if severe long-term: memory problems, sensory problems . - “dementia pugalistica”

7. How does traumatic brain injury develop ? • direct, mechanical injury to neurons (axons, dendrites or soma) • damage to blood supply deprives neurons and glia of nutrients • Overactivity of glutamate receptors • Activation of NMDA-type glutamate receptors • Inflow of too much Ca2+into neurons • activates death enzymes that break down neuron • Impairs neuron ability to meet energy requirements • Triggers cell death A little bit of Ca2+ inflow is good at the right time, too much is toxic

8. Strokes disruption of blood flow in brain 3rd leading cause of death in adults • Hemorrhage: bleeding in brain, blood vessel ruptures • - can be from traumatic injury to blood vessel • - can be from “aneurysm” • weakening of blood vessel wall, balloonlike • dialation forms and can burst • caused by some infections, toxins like cigarette • Smoke. Can also be develomental abnormality.

9. 2. Ischemia: blood flow to a brain region is blocked - a blockage that comes from another part of the body is an “embolism” (vs. thrombosis) for example, a blood clot in leg, can travel to brain and cause ischemia is gets stuck in a smaller artery. “arteriosclerosis”: fat deposits in brain blood vessels grow over time and block blood flow. (can become embolism) How does a loss of blood supply kill neurons ? -deprived neurons become overexcited, release glutamate -glutamate activates NMDA receptors - and because no blood supply=no energy, no reuptake of glutamate

10. Dementias deterioration of intellectual abilities due to disease *memory, judgment, concentration *usually w/ personality changes, emotional instability What causes dementia ?? 12-15% stroke 12-15% Huntingtons, Parkinson’s Diseases (motor diseases) * other similar disease that are rare • >5% Korsakoff’s syndrome • severe anterograde amnesia Alzheimer’s Disease (leading cause of severe dementia in U.S.) - +1% of population, most over 65 yrs old

11. Causes ? We do NOT know what causes Alzheimer’s Disease ! But, we know that…: • Risk of developing it is heritable there is a “genetic” factor involved 2. Some AD patients have a specific genetic problem That can cause early-onset and severe form (~45 yrs old) 3. But, many other AD patients don’t have family members with AD and don’t have an identified genetic problem Alzheimer’s Disease is probably just 1 term used to describe the symptoms of lots of different diseases that cause brain damage and similar symptoms.

12. I. Plaques:most AD patients have plaques in parts of the brain that show cell loss in early AD: medial temporal lobe areas (hippocampus) and cortex in late AD: lots of areas (all areas that produce or receive acetylcholine) Key to understanding plaques: • Plaques are made of a protein called beta-amyloid • 2. Beta amyloid come from a normal protein that neurons need to function normally, • called Amyloid Precursor Protein (APP) • 3. but, APP is cut by enzymes into abnormal amounts of beta amyloid. • -neurons can get rid of a small amount of beta amyloid, but • if there is too much, beta amyloid clumps together to form plaques inside of neurons. • Neurons don’t function normally and die-off

13. Normal Human Gross Pathology: Ventricles larger gray matter loss white matter loss Human with Alzheimer’s Disease

14. Parkinson’sDisease mentioned in the Ayurveda, the system of medicine practiced in India as early 7,000 years ago , and in the first Chinese medical text, Nei Jing, which appeared 2500 years ago "An Essay on the Shaking Palsy," published in 1817 by a London physician named James Parkinson,

15. Symptoms • Difficulty initiating movement • Shuffling gait • “Cogwheel” rigidity • Tremor at rest • Advanced stages may include psychiatric complications • depression • hallucinations • Paranoia • Cognitive decline http://www.youtube.com/watch?v=13ftfmYwfaw

16. Incidence • Onset usually appears after age of 40 years • but can begin at any time including childhood when it is termed juvenile parkinsonism • affects 1% aged 50 years and over • 10% aged 60 years and over may have undiagnosed, early stages of the disease • about 1½ times more common in men than in women

17. Subtypes • Primary (idiopathic- most common) • unknown origin but not induced by obvious stimulus • Secondary (parkinsonism) • related to drugs, stroke, or trauma, other stimuli • Familial • genetically linked • accounts for < 20% of the diagnosed cases

18. Progression: identified too late ? • Considerable dopamine loss must occur before the disease is apparent • clinical diagnosis is usually made after  80% loss in basal ganglia dopamine content • symptoms may emerge after a 60% reduction in basal ganglia dopamine content • The disease is probably present > 20 years before diagnosis

19. PET Scan Loss of cellular activity in the Basal Ganglia

20. AphasiaAphasiaDisorder that results from damage to portions of the brain that are responsible for language (for most it’s the left side of the brain)

21. Aphasia • Damage to temporal lobe may result in fluent aphasia called (Wernicke). People will speak in long sentences that have no meaning and even create made-up words • Non-fluent aphasia is called (Broca’s). Phrases make sense but are produced with great effort. They omit words such as is and and. Example: They may say Walk Dog (meaning I will take the dog for a walk) • How to help: Simplify language,repeat, stroke clubs

22. Brain Disorders • Dyslexia: reading disorder, more common in boys, genetic, sound recognition plays a role, less activity in the left hemisphere • Huntingtons Disease: is a progressive brain disorderthat causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. • https://www.youtube.com/watch?time_continue=11&v=_IhQZ_e1yq4

23. Blog Post for this week-Pick ONE • If you could test to predict whether you were endowed with a genetic disorder would you take the test? • Think of a task you feel you do not do well. For example, you might choose math, singing or playing soccer. How does this make you feel? Do you think that your brain may be “lacking” something needed to do well in this area or do you think you simply need more education and/or practice in this area?