Brain Injury 101 The Universe Between Our Ears: Functional Neuroscience

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Brain Injury 101The Universe Between Our Ears
Functional Neuroscience

• Paul F. Aravich, Ph.D.
• Professor of Pathology and Anatomy
• Professor of Internal Medicine, Division of
  GeriatricsEastern Virginia Medical School
• Norfolk, VA 23507
• Chair, Neurobehavioral Committee, Virginia Brain
  Injury Council
• Chair, Va. Public Guardian Conservator Advisory
  Board
• 19th Annual State of the States in Head Injury
  National Conference
• National Association of State Head Injury
  Administers
• Williamsburg, VA 9/10/08

aravicpf_at_evms.edu
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Outline learning objectives to describe
This presentation is dedicated to the memory of
Mary Draffin tireless advocate for people with
brain injuries

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral problem

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The Universe Between Our Ears

The last great frontier of science
Andromeda Galaxy, Univ. Arizona Web Site, 10/31/98
Brain. http//www-medlib.med.utah.edu/WebPath/CNSH
TML/CNS088.html
M31 Galaxy
How far can the unaided human eye see? M31 2
million light years X 6 trillion miles/light year
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Neurological possibilities

• 100 billion neurons Milky Way Galaxy
• 1 trillion supportive cells glia
• 1014 synapses 1 quadrillion
• but, synapses always changing dynamic
• conclude infinite possibilities
• "nothing is more constant about the nervous
  system than its ability to change1
• Called hope
• Called neural plasticity
• If you dont use it you lose it
• 1p 1475, Barinaga. Science 1994 2661475-1476

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Uniqueness of every human brain

• All people without brain injuries have unique
  brains
• All people with brain injuries have unique brains
• If youve seen one person with a brain injury,
• Youve seen one person with a brain injury

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What is the brain made of?

• Mostly Water Cholesterol
• molecules, which are made of
• Atoms, which are made of
• Incredible forces

http//web.mit.edu/newsoffice/2003/elegant-1022.ht
ml
String theory
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question what do you look for when you see a
person with a brain injury?

• Goethe You see what you look for
• Do you look for
• Cognitive/emotional problems, paralysis, wheel
  chairs
• Or Do you look for greatness in people w/ BI
• And Do you look for greatness in
• Families
• Yourself

You can do no great things, only small things
with great love. Mother Theresa
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Family response to profound disabilityFay Gillis
Wells aviatorwith Amelia Earhart in 1929 DOB
10/08

• Pursue the completely unexpected
  opportunities that come along in life.
• 10/29/02 email to Paul Aravich
• Sartre We are condemned to freedom
• Families can crawl into caves or
• Become empowered change agents
• The terrorism of disease/trauma
• Steal Life, Liberty the Pursuit of Happiness1
  since we need a
• Government of, by For2.. disabled as well as
  abled people

Photo Age 90. Died 94
1Declaration of independence. 2Lincolns
Gettysburg Address
Morell/Leen Natl Geographic 1998 Jan. p. 131
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Successful aging
A goal of all of Gods creatures, great small

• For people w/o disabilities. And
• For people w/ disabilities

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Expansion of people aging w/ disabilities

• Face lots of barriers to health care
• More rapid deterioration over time?
• Do developmental/acquired brain injuries
• Accelerate brain senescence or do they
• Add to normal brain senescence
• Who will take care of them?
• I pray a prayer no parent prays, I pray my son
  dies before me
  
  Older parent of a developmentally disabled adult
  son to General Assembly Virginia
• See Aravich McDonnell. Successful aging of
  individuals with brain injury. Brain Injury
  Professional, (the official publication of the
  North American Brain Injury Society).
  20052(2)10-14

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Outline learning objectives to describe

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral problem

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Stars of this universe neuron
http//www.nida.nih.gov/Teaching2/largegifs/slide5
.gif
Sends an electrical signal that travels a couple
hundred miles/hr
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Diffuse axonal injury
Dendrites
Cell body

• Angular forces
• Disrupts white matter surrounding axon myelin
• Axons swell
• Focal hemorrhages

Axon
Brain Facts. Society for Neuroscience
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Neurotransmission focus of medications(e.g.,
dopamine)
axon terminal
http//www.nida.nih.gov/Teaching2/largegifs/slide7
.gif
synapse
postsynaptic receptors
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Forgotten cells glial cells

• Many more glia than neurons
• Myelinating cells (make white matter)
• CNS Oligodendroglia cells
• Peripheral nervous system Schwann cells
• Microglia
• technically not glia more similar to
  macrophages, developmentally
• respond to injury can make original insult worse
• Astrocytes protoplasmic in gray matter fibrous
  in white matter
• also respond to injury can make original insult
  worse
• Various other functions
• Ependymal cells (help make CSF) adult stem
  cells?
• Radial glia developmental guidance factors

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Brain cancer Gliomas

• Account for about
• 40 of all brain tumors and
• 77 of all malignant brain tumors
• Types, e.g.
• Astrocytoma 35 of brain tumors
• -most common glioma
• -high grade astrocytoma Glioblastoma multiforme
• -Glioblastoma most common adult malignant brain
  tumor
• Oligodendroglioma 4 of all brain tumors
• Ependymoma 2 of all brain tumors
• http//www.cancer.org Am Cancer Soc. What are
  brain and spinal cord tumors

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Cranial Spinal nerves
12 pairs of Cranial nn
31 pairs of Spinal nn
Brain Facts. Society for Neuroscience, 1997, p. 11
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Whats up w/ the armpit?

• Is it just a hairy, smelly place?
• How did Michelangelo create David?
• Brain talks to spinal cord
• Spinal cord talks to hands via
• Spinal nerves traveling though armpit
• How did Michelangelo create David?
• Through his armpit

Galleria dell'Accademia, Florence
http//www.fionline.it/turismo/musei-fi/mus01uk.ht
ml
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Motor Control chain of 2 neurons

• Upper motor neurons
• Located in motor cortex
• Axons cross midline
• Lower motor axons
• to muscles on same side

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Brain injury Spastic paralysis

• Spasticity
• ?muscle tone restricted to limbs
• Flexed elbow, wrist, digits
• Extended knee
• Foot drop
• Exaggerated reflexes

Fig. 6-6, p. 68. Young/Young. Basic Clinical
Anatomy. Williams/Wilkens, 1997.
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Outline learning objectives to describe

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral problem

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Brain injury

• That which is among the most miraculous of things
• Is also among the most fragile
• Easily injured
• Once injured
• All the kings horses and all the kings men have
  a tuff time putting it back together again

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Neurological/psychiatric costs each is a brain
injury

• suffering
• largest amount of health care dollars
• gt1/2 all US health costs direct/indirect
• Dana Alliance for Brain Initiatives Alliance
  for Aging Res. www.dana.org.

1st Office of Homeland Security. National
Institutes of Health fighting the terrorism of
disease trauma
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Types of Brain injuries

• Congenital Downs, other genetic, neural tube,
  fetal alcohol, cerebral palsy, autism, fragile-X,
  prenatal malnutrition, prematurity
• Degenerative Alzheimers, Parkinsons, HD, ALS
• Acquired
• Stroke
• Traumatic brain injury (TBI), including shaken
  baby syn
• Other ABI anoxia, metabolic (liver/kidney),
  tumor, infection, electrical, toxic chemicals etc
• Chemical dependence
• Mental illness

Does language get in the way?

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Suicidal CNS responses to brain injury

• short-term, auto-destructive processes, e.g.,
• free radicals, excitotoxicity, inflammatory
  mediators
• Experimental treatments, e.g., hypothermia to
  slow down
• worsen effects of original insult
• e.g., ? brain swelling, intracranial pressure
• critical need for immediate treatment
• One of the main outcomes of basic animal
  research during the Decade of the Brain

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256,00 Virginians gt age 18

• Living w/ complications of TBI stroke
• Does not count other forms of ABI
• Does not count DOD TBI

• Conclude
• More than quarter million Virginians gt age 18
• living w/ an ABI disability

Source, Neurobehavioral Committee of the
Virginia Brain Injury Council
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TBI, Iraq Afghanistan1

• unprecedented of TBIs1
• People living instead of dying
• 75 TBI mortality rate in Vietnam2
• Better protective equipment1
• Better acute medical care1
• Issue now long-term care1
• We need to support defend3 the rights of
  disabled veterans
• America
• We can do better

http//www.erichufschmid.net/Iraq_Car_Bomb_From_He
ll.JPG
1Drazen. N Engl J Med. 2005 May 19352(20)2121
2Okie. N Engl J Med. 2005 May 19352(20)2043-7
3DoD Oath of Office
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Meninges bleeds
Dura mater tuff mother
Photo by Paul Aravich EVMS
Wooden applicator in subdural space between dura
arachnoid
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Meninges bleeds, cont.
Dura mater tuff mother
Photo by Paul Aravich EVMS
Wooden applicator in subdural space between dura
arachnoid
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Bridging veins rupture cause subdural bleed
Dura reflected up
Photo by Paul Aravich EVMS
Photo by Paul Aravich EVMS
Dura mater
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Subdural bleed most common intracranial bleed
Dura mater
Photo by Paul Aravich EVMS
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Arachnoid mater
Blue pin through Arachnoid mater
Post-central gyrus
Photo by Paul Aravich EVMS
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Arachnoid mater clinical correlates

• Meningitis infection
• Infection/inflammation of arachnoid/pia
  (leptomeninges)
• Bacterial worse than viral
• Issue of vaccinating college students in dorms
• Meningioma tumor
• From arachnoid mater
• or from arachnoid cells of choroid plexus of
  ventricles
• Most common brain tumor in adults
• Slow growing
• Usually (85) benign but can still injure brain

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Subarachnoid bleed, base of brain hemorrhagic
stroke or TBI
Anterior
Photo by Paul Aravich EVMS
Posterior
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Stroke belt Southeast
http//www.strokecenter.org/pat/stats.htm
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Causes of TBI

• Falls 281 Major issue for people w/
  disabilities
• Vehicles 201
• Assaults 111 including shaken baby syndrome
• Firearms 102
• 1 leading cause TBI death- 44 TBI deaths2
• 2/3 by suicide2

Each relates to children as well as to adults

• 1http//www.biausa.org/word.files.to.pdf/good.pdfs
  /generalbraininjuryfactsheet2005.pdf
• 2http//www.cdc.gov/Migrated_Content/Fact_Sheet/Fr
  eeform_Fact_Sheet_(General)/Traumatic_Brain_Injury
  _updated_May_2004.pdf

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Outline learning objectives to describe

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral problem

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Stem cells

• self-renewing
• Become different cell types
• differentiation
• Pluripotent stem cells
• AKA embryonic stem cells
• Make many kinds of cells
• Multipotent stem cells
• AKA adult stem cells
• restricted potential

http//www.nih.gov/news/stemcell/scireport.htm
NIH Stem Cells Scientific Progress and Future
Research Directions
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Pluripotent Stem cellsembryonic stem cells
Blastocyst

• Pre-implantation embryo (blastocyst)
• Usual source Fertility clinics
• 100 cells size head of pin
• Depending on how grown
• Become most any cell type

Fig. 2.10 a,b, p. 35. Sadler. Med. Embry. 7th ed,
1995
Thomson et al. Science 1998 Nov
6282(5391)1145-7 Erratum in Science 1998 Dec
4282(5395)1827.
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Embryonic stem cell transplants

• TBI?
• Stroke?
• Alzheimers?
• Parkinsons?
• Issue of immune rejection

http//www.sfn.org/briefings/stemcell.html
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Multipotent (adult) stem cells umbilical cord
blood less prone to rejection vs other
multipotent cells
http//www.cordblooddonor.com/index/art/stemcellim
age.jpg
www.humpath.com/IMG/ jpg/normal_placenta_0501.jpg
Placenta cord
Freeze/store 1,500 100/yr
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Multipotent (adult) stem cells hematopoietic
stem cells

• In Bone marrow
• Leukemia routine transplants
• Harvest cells
• Kill cancer cells radiation/chemo
• Return saved cells
• Can make neurons
• Least controversial transplant

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Multipotent (adult) stem cells in brain
subventricular zone (yellow dots)
http//universe-review.ca/I10-66-nstem.jpg
eye
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Stroke (adult mouse) causes neurogenesis near
lateral ventricles (LV)
New neurons in adults migrate to areas of damage
Fig. 2. Zhang et al. J Neurosci 2004
24(25)5810-5815
How do we induce more guide them to injury?
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Reprogram adult cells to embryonic cells
Not Therapeutic Cloning
Nuclear reprogramming

• Insert 4 genes linked to development
• via engineered viruses retro-
  lentiviruses
• But concerns re cancer other complications

Skin cells to
http//newsimg.bbc.co.uk/media/images/44251000/gif
/_44251016_stem_cells_416.gif
The new, new thing
Embryonic stem cells
Takahashi et al. Cell. 2007 Nov 30131(5)861-72
Yu et a. Science. 2007 Dec 21318(5858)1917-20
. Epub 2007 Nov 20
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Outline learning objectives to describe

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral problem

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Neurobehavioral Problems

• Behavioral and psychiatric complications of BI
• Among most prevalent/disabling features
• Cognitive
• Emotional
• Social
• Frequently misdiagnosed or not treated
• Mindless neurology and brainless psychiatry
• Filley CM. Neurobehavioral Anatomy. Ed 2, Univ
  Press of Colorado. 2000

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Neurobehavioral problem compounded by

• Discrepant insurance reimbursement
• lack of mental health parity
• Lack of Medicaid support in many states
• Lack of home/community supports

Conclusion Neurobehavioral problems are
treated by professionals who
have not been educated in brain injury and in
settings not designed to address brain injury.
Natl Assoc of State Head Injury Administrators
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Neurobehavioral issues

• Neurobehavioral problems woefully under
  addressed
• There is a significant unmet need for specialized
  assessment/treatment programs
• Lack of expertise can
• Worsen behavioral problems or
• Cause overly restrictive environments

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Challenging behaviors damage to Prefrontal
cortexseparates us from the animals
Beardsley Scientific American 1997 August, p. 80
Executive functions
Impulse control
Social withdrawal
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Prefrontal lobotomy restrictive environments

• Dehumanized psychotic patients
• did not improve, only easier to manage
• gave Moniz (Mo-Neez) 1949 Nobel prize
• What about pharmacological restraint

• See PBS.Org American Experience

Others could do 75 a day
Even did kids who may have simply had ADD
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Learning/memory problems
Hippocampal formation
Photo by Paul Aravich EVMS
Temporal lobe The thumb of the cortical boxing
glove
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Hippocampus most of brain removed
Photo by Paul Aravich EVMS
Anterior
Posterior
Right amygdala
Right Hippocampus proper
Lateral view
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Photo by Paul Aravich EVMS
Right hippocampus proper
Lateral view
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Hippocampus
Posterior
Anterior
Superior view w/ most of brain removed
Photo by Paul Aravich
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Stress hippocampus w/ or w/o a TBI

• Glucocorticoids toxic to hippocampus
• How many survivors suffer from stress of
• Social isolation
• Transportation
• Housing
• Job training
• Financial
• Non-human primates. Sapolsky. J. Neurosci.1990
  10 2897. But see Leverenz et al. J Neurosci. 1999
  Mar 1519(6)2356-61

front
Sundsten JW and Mullignan KA. Dorsal hippocampal
dissection 8. Neuroanatomy Interactive Syllabus.
http//www9.biostr.washington.edu/da.html
hippocampus
back
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TBI mandate community-based services

• Olmstead Supreme Court decision 6/22/99
• its the law
• No qualified person w/ a disability shall be
  denied community-based care
• otherwise discrimination
• Problem not enough community providers

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Dentate gyrus (part of hippocampal formation)
Left Hippocampus proper
Posterior
Photo by Paul Aravich EVMS
adult stem cells increased by sensory enriched
environments
Anterior
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Social/environmental deprivation physical harm
to the brain. How many are alone?
Normal
Deprived
Brain Briefings, Society for Neuroscience, 12/97
PET Scan normal girl vs socially isolated girl
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Clinical implications

• The human brain is a social brain
• Is psychosocial enrichment a standard of care?

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Honduran mother after being told son has
irreversible brain damage (Cerebral Palsy)
No info/resources provided mom Similar to USA
Photo Mina Tabibi MPA 2007
3 kinds of people in the world -those
who have been caregivers, -those who are
caregivers -those who will be care
givers. Roselyn Carter
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Amygdala attaches emotional significance to
events PTSD
Hippocampus proper
Projects directly indirectly to hippocampus to
enhance memory for emotional stimuli
Reading Faces, Brain Briefings. Society for
Neuroscience http//web.sfn.org/content/Publicatio
ns/BrainBriefings/reading.htmlfullsize
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Amygdala
Photo by Paul Aravich EVMS
Right hippocampus proper
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Amygdala
Left amygdala
Posterior
Anterior
Superior view w/ most of brain removed
Right amygdala
Photo by Paul Aravich
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Cingulate gyrus Depression
Depression Anterior cingulate gyrus
anterior
posterior
pons
medulla
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Depression damages hippocampus w/ or w/o TBI

• toxic

Brain Briefings, Society for Neuroscience, 11/96
hippocampus
In the thumb of the boxing glove (temporal lobe)
anti-depressant drugs protect against volume loss
Sheline et
al. Am J Psychiatry August 2003
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Depression lesion left prefrontal cortex
Photo by Paul Aravich EVMS
The so-called catastrophic response
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Classic cortical language areas aphasias
Burt. Textbook of Neuroanatomy. Saunders, 1993,
p. 469
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Language regardless of handedness on Left side
Anterior
Posterior
Photo by Paul Aravich EVMS
Note Right side puts emotional tone in language
Note Right side perceives emotional tone in
language
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Chemical dependency injures reward circuitry
Photo by Paul Aravich EVMS
thalamus
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Need systems of neurobehavioral care Virginia
Brain Injury Council Focus

• 1. Intensive neurobehav programs for high needs
• 2. Residential neurobehav. prog for moderate
  needs
• 3. Community-based programs for low needs
• A Systems approach
• Non-linear
• Transition from any level to any other level as
  needed

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The systems of care approach

• Beyond the traditional skilled-nursing facility
  model
• Direct interaction w/ experts in the new
  discipline of neuropsychiatry
• e.g., Understand unique medication needs
• Staff/providers trained in neurobehavioral
  approaches
• e.g., Understand positive environmental controls
  etc
• A focus on the whole person
• A focus on least restrictive environments
• A focus on public and private funding supports

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Neurobehavioral care other questions

• Should it be called
• Behavioral psychiatric problems of brain
  injury?
• Is the stigma of mental illness getting in the
  way of neurobehavioral reform
• Is neurobehavioral reform part of mental health
  reform
• Are greater state agency partnerships needed
• Is turf getting in the way of Neurobehavioral
  reform
• Are greater advocacy partnerships needed

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Parallel, non-intersecting universes

• Developmental disability advocates
• TBI advocates
• Stroke advocates
• Alzheimers advocates
• Mental Illness advocates
• Competition vs Cooperation
• American Brain Coalition

http//nastystart.org/images/news/paralleluniverse
s04162003.jpg
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question do you look for greatness in the person
with challenging behaviors?

• Goethe You see what you look for
• Do you look for
• Cognitive/emotional problems, paralysis, wheel
  chairs
• Or Do you look for greatness
• And Do you look for greatness in
• Families
• Yourself

You can do no great things, only small things
with great love. Mother Theresa
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Outline learning objectives to describe

• Possibilities of human brain
• Selected brain basics
• The many ways the brain can be injured
• Stem cells
• Challenging behaviors the neurobehavioral
  problem
• We the People of the United States, in Order to
  form a more perfect Union, establish Justice,
  insure domestic Tranquility, provide for the
  common defence, promote the general Welfare, and
  secure the Blessings of Liberty to ourselves and
  our Posterity
• Preamble US Constitution

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Good neuroscience/health sites to Google

• Society for Neuroscience
• Dana Alliance for Brain Initiatives
• Brain Injury Association of America
• Alzheimers Association
• National Institute of Mental Health
• National Alliance for the Mentally Ill
• National Institute of Drug Abuse
• National Institute on Alcohol Abuse and
  Alcoholism
• National Institute of Neurological Disorders and
  Stroke
• Nutrition.gov
• American Dietetic Association
• National Heart, Lung, and Blood Institute Obesity
  Guidelines
• American Heart Association
• American Lung Association
• American Diabetes Association
• Administration on Aging
• MedLine Plus (NIH site great for all
  diseases/pathologies)