Causes of brain dysfunction

Encapsulated tumours

• Encapsulated: some tumours grow to have membranes and therefore are benign (non cancerous/rarely grow back when removed)

Tumours or neoplasms = our cells growing/replicating when they don’t need to

• eg. Meningioma - grows inbetween the meninges of the brain

Infiltrating tumours

Non-encapsulated tumours

Grow diffusely through surrounding brain tissue

• most cells continue growing uncontrolled - hard to distinguish between healthy and non-healthy tissue

• malignant: grows rapidly, high likelihood of that the tumour will come back

Metastatic tumours

All malignant

• tumour started elsewhere and traveled to new location

• Some infiltrating brain tumours grow from tumour fragments carried to the brain from another body part via the blood stream

• Commonly originate from breast/lung cancers

Glioblastoma

Most common type of brain tumour in adult

• caused by over growth of astrocytes

• Very aggressive = ~14 mouth survival timeline

Can create vaccine that targets the 1 protein (Survivin)

• not a cure, but increased life span in 93% patients

  • Targets apoptosis

Strokes

Sudden onset cerebrovascular disorder → blood flow to brain

• infarct: area of dead/dying tissue (dies within 4 minutes)

  • Doctors aren’t interested in saving

• Penumbra: dysfunctional area surrounding the infarct, tissue in penumbra may survive

  • Area that doctor is interested in saving

Types of strokes

Ischemic: resulting from cerebral ischemia - blockage inside blood vessel → stops blood flow in that area of the brain

Hemorrhagic: resulting from cerebral hemorrhage - loss of blood in area

• blood now in brain which is toxic to neurons/cells

• Infections can grow

• Blood spraying onto soft tissue can damage the brain

Infarct area

Area of dead/dying tissue in a stroke

• 4 minutes till death

Penumbra

Dysfunctional area of surrounding the infarct

• tissue in penumbra might recover or die

• Area that doctor wants to save

Ischemic

Type of stroke

• resulting form cerebral ischemia

• Blockage inside of a blood vessel

Hemorrhagic

Type of stroke

• resulting from cerebral hemorrhage

• Loss of blood in area (Bc blood now is in the brain rather than within the vessels

  • Blood is toxic to neurons/cells → infection can grow

  • Pressure of the blood escaping the vessel can cause it to be damaged

Cerebral hemorrhage: Aneurysms

Distortion/stretching of an artery with the blood

• like water balloon, vessels can burst/breark with too much pressure

• Can push into other areas of brain (pushing on cranial nerves)

Can be congenital (born with it) or can develop later in life

Risk factors of aneurysm

Diabetes, smoking cigarettes, alcohol, high blood pressure and aging

Aneurysm treatment

1. Clipping

2. Endovascular coiling

Aneurysm Treatment - clipping

Tying end of “water balloon” to prevent it from bursting

• we clip the end of the blood clot which makes the blood congeal

Lower rate of reoccurrence

• requires invasive open brain surgery (con)

Aneurysm treatment: endovascular coiling

Incision on femoral artery (in the leg), place a tube that runs all the way up your body and to the area of aneurysm

• Metal in the coils react with the iron blood and causes it to clot/congeal

Pros/cons

• higher change of reoccurence

• Doesn’t require open brain surgery

Cerebral ischemia

A disruption of blood supply to some area of the brain

Comes in 3 flavours

1. Thrombosis

2. Embolism

3. Arteriosclerosis

3 can interact with 1/2

Thrombosis

Type of cerebral ischemia

• when a blood clots within a blood vessel and blocks the flow

• Causes cerebral ischemia

Embolism

Type of cerebral Ischemia

• air bubble/fat/tumour/other materials that stick/block blood vessel

Arteriosclerosis

Type of cerebral ischemia

• when walls of the vessels thicken, causing blood flow to be restricted and blocked

3 properties of Cerebral Ischemia damage

1. Sometimes takes a while to develop (become known)

2. Damage is more likely in some parts of the brain

   1. Hippocampus (less capillary dense)

3. Mechanisms of ischemia is varied between brain areas

   1. Excitotoxicity and apoptosis

Why is too much activity in the brain toxic

Strokes in certain areas of the brain can cause too much activity in surrounding areas

• w/o blood going to areas of brain (stroke) the brain doesn’t get enough oxygen/glucose which causes a decrease in ATP

• If ATP production slows, our resting membrane fails → moving us closer to 0 = more AP firing

• W/ more AP = more glutemate = release of NMDAR’s

• NMDAR allows more Ca+ to enter

• Too much Ca+ can trigger a self-destruct mechanism (Apoptosis)

• All of this causes the cells to destroy themselves

How we fight against cell death (apoptisity)

We created Glutemate Antagonist drugs to block NMDA receptors

• don’t work as well bc Ca+ also signals vesicles to fuse to teh cell membrane when transmitting information

Apoptosis

Cell death

• all cells have a self-destruct mechanism that occurs when triggered

• Too much Ca+ can trigger apoptosis

Open head injuries

Penetrating or perforation (straight through) head injuries

• high risks of infection

• High velocity worse than low

• 9/10 people die

• As they enter the brain they also bounce around surrounding brain area

Closed-head injuries: contusions

Contusions: bruise

• damage to the cerebral circulatory system, producing internal hemorrhaging and a resultant hematoma (bruise that develops into a blood clot)

• Occurs where teh brain slams against the skull

Has 3 types

1. Epidural

2. Subdural

3. Intracranial

Epideral (closed head injuries)

Bruise/blood clot that develops between skull and meninges

Subdural (closed-head injuries)

Bruise/blood clot that develops between meninges/brain

Intracranial (closed-head injuries)

Bruise/blood clot developed within the brain

What is a hematoma

Bruise that develops into a blood clot

Coup injuries

Area of head that meets brain

• when object hits us

Coup contrecoup injuries

When we hit a steady object, our brain slides forward and hits the front of our skull and bounces back to hit the back of our skull as well

• only when we hit something (wall)

Mild Traumatic Brain Injury (mTBI)

When there is a blow to head but no evidence of contusion or other structural damages

• even when there is harm

Not a concussion

• you can injure brain w/o it being a concussion

• Slower recovery ~12-18 month to fully recover

• Can have subconcussive mTBI: still brain injury, but not enough for it be considered a concussion

Chronic Traumatic Encephalopathy (CTE)

A progressive, irreversible, neurodegenerative disease from repeated head trauma

• common in combat sports → also seen in common people

CTE development steps

1. Confusion, disorientation, headaches

2. Lapses in memory, social norms, impulsivity, judgement

3/4 . Progressive dementia, movement disorders (Parkinson’s), speech disorders, depression (suicidal ideation)

Common for patients to feel aggressive/jealous/paranoia

CTE: Tau/Neurofibrillary tangles

Tau stabilizes cytoskeleton

• when Tau is tagged/marked it freaks out and stops binding to cytoskeleton and to each other

  • Making Tau tangles

• Also seen in Althismers and Parkinson’s

• Tau builds up in the sulci of cerebral cortex → minor bleeds from damages brain

Tau and PET scans

Starting to develop ways to track Tau development with pet scans

• radioactive tracer for tau to study CTE