The Neurobiology of Concussions

Question 1

What is a concussion?

Answer 1

Concussions can also be referred to as mild traumatic brain injuries (mTBI)

• L. Concutere, to shake violently
• L. Concussus, action of striking together

Question 2

What does a concussion do to the brain ?

Answer 2

Defined as a biomechanically induced transient disturbance of neurological function.
- May or may not be associated with loss of consciousness (LOC);
- Temporary loss of brain function;
- Produce a variety of physical, cognitive and
emotional symptoms (often subtle);
- Symptoms subside naturally.

Question 3

What causes a concussion?

Answer 3

Rapid acceleration and/or deceleration of the brain.
Resulting in brain colliding with skull, both the front and back (or side to side)
- Coupe-Contre Coup
- CSF, meninges and skull cannot brace this type of impact
Bruising and swelling of brain tissue follows and may persist for up to 48 hours;
- Brain contusion and cerebral edema; - Increased intracranial pressure.

Impact can be direct or indirect, it doesn’t matter (sport related collision vs. blast exposure at war).
Impact can be linear, rotational or angular, this does matter.
- Or, probably, a combination of all;
- Direction of force is extremely important for predicting extent of injury/recovery.

Question 4

Does Direction Matter

Answer 4

Direction of force will dictate presenting symptoms, long-term consequences, extent of damage and rate of recovery.
This makes it difficult to compare concussions between patients (in humans).

Question 5

Rotational Forces

Answer 5

The magnitude of rotational force is thought to dictate concussion severity.

Question 6

Diffuse Axonal Injury (DAI)

Answer 6

Shearing forces cause axons to detach from cell
body;
- Damaged axons display indiscriminate release of
the excitatory neurotransmitter glutamate;
- Excitotoxic lesions subsequently occur from 24-48
hours post injury.

Question 7

Parts of the brain most affected by rotational forces

Answer 7

midbrain and diencephalon.

• Disruption of normal cellular activities here is thought to produce LOC;
• Also damages frontal and temporal lobes.

Question 8

subdural hematoma

Answer 8

Unrestricted movement of the of the head results in axon shearing, often leading to subdural hematoma collection of clotted blood and accompanying increased pressure on the brain.
Brain contusions are typically viewed as the hallmark of brain damage following a brain injury.

Question 9

Epidural hematoma

Answer 9

Epidural hematoma results from the collection of blood between the dura mater and the skull.

Question 10

The Aftermath – Acute Metabolic Cascade

Answer 10

Acutely, a concussion can lead to neural & vascular tissue damage, leading to a distortion of cell membranes.

• Neuronal activity picks up (glutamate);
• Cerebral blood flow is interrupted (hematoma);

Question 11

What are concussions associated with

Answer 11

Concussions are associated with an indiscriminate release of glutamate which produces a cascade of events known as the metabolic cascade, leading to a cerebral energy crisis.

Question 12

What is Glutamate

Answer 12

Glutamate is the main excitatory neurotransmitter in the brain. It is present in more synapses than any other
neurotransmitter.

Question 13

What happens when Glutamate released

Answer 13

Once released into the synaptic cleft, glutamate can bind to three post-synaptic receptors:
1. AMPA receptors;
2. NMDA receptors;
3. Kainate receptors.
All 3 receptors allow Na+ entry into the post-synaptic cell
and therefore cause depolarization and excitatory post-synaptic potentials.
NMDA receptors are also permeable to calcium.

Question 14

Glutamate Excitotoxicity

Answer 14

Too much glutamate being released can cause damage to surrounding neurons.
Excitotoxicity can occur with overexposure to glutamate (or other excitatory AA’s), caused by a prolonged depolarization of the postsynaptic neuron.
When neurons are subjected to prolonged stimulation
by glutamate, a large % of cells die via 1 of 2 mechanisms:
1. Necrosis and Apoptosis

Question 15

Necrosis

Answer 15

Necrosis: characterized by rapid lysis of the cell due to osmotic swelling;

Question 16

Apoptosis

Answer 16

Apoptosis: delayed cascade of biochemical events that leads to DNA breakup and ultimately cell death.

Question 17

Glutamate activation of NMDA receptors

Answer 17

Glutamate activation of NMDA receptors can, in some cases, allow the entry of calcium (Ca2+) into the cell.

At large enough concentrations, Ca2+ is extremely toxic to a cell:

• Overactivation of NMDA receptors;
• Massive influx of Ca2+ (and Na+, and K+ efflux);
• Ca2+ is sequestered in mitochondria and interrupts normal function;
• ATP production is hindered;
• Can lead to initiation of apoptosis.

Question 18

The Aftermath – Energy Crisis

Answer 18

Recall: your body spends an extraordinary amount of energy (ATP) fueling Na-K pumps. Following a concussion, and an indiscriminate release of glutamate, most of the surrounding
neurons are depolarized and fire action potentials.
Na-K pumps are working in overdrive to restore ionic homeostasis becomes this requires a ton of
ATP.
Increased demand for ATP results in massive increase in glucose metabolism.

However, increased demand for glucose comes at a time when cerebral blood flow is reduced and mitochondria are dysfunctional (double whammy);
Hypoglycemia ensues, leading to cognitive deficits and an energy crisis that leads to secondary injuries.

Question 19

Secondary Injuries - BBB Permeability

Answer 19

Anaerobic glucose metabolism (glycolysis) involves production of lactate to lactic acid.
Overproduction of lactic acid results in acidosis, and subsequent damage to the blood brain barrier (BBB).
BBB permeability follows, leaving organism extremely vulnerable to outside toxins.

Question 20

Secondary Injuries - Inflammation

Answer 20

Following brain injuries, a patients condition may deteriorate in stages, which suggests that brain injuries result in various waves of potential damage.
- Primary vs. secondary effects.
Secondary effects may take days, weeks or months to develop, and can persist for weeks, months and even years.

Question 21

Clinical Symptoms of mTBI

Answer 21

Symptoms of a concussion are individualistic, as they are entirely dependent on location of structural damage.
A patient may experience:

• Headache, pressure in the head is a vascular injuries;
• Temporary loss of consciousness (LOC) is a brain stem;
• Confusion is a corpus collosum;
• Amnesia surrounding the event is a hippocampus, frontal lobes;
• Ringing in the ears is a temporal lobes;
• Nausea and/or vomiting is a area postrema;
• Changes in mood and emotional disturbances is a amygdala

Question 22

Detection & Diagnosis

Answer 22

Sport Concussion Assessment Tool – 5th Edition (SCAT-5)
- The SCAT-5 is a standardized tool for evaluating concussions;
- Designed for use by physicians;
- Pre-season SCAT-5 scores are useful for comparing pre/post injury
results;
SCAT-5 involves:
- Checklist for observable signs of trauma;
- Memory assessment;
- Glasgow Coma Scale (GCS) assessment;
- Symptom inventory (completed by athlete); - Battery of cognitive screening tests;
- Neurological screen.

Question 23

Second Impact Syndrome

Answer 23

Prior concussions increase the likelihood of a 2nd concussion and cause greater morbidity in both human and animal models.
Repeated concussions have a cumulative effect on the human brain.
Second Impact Syndrome (SIS)
- Occurs when an individual suffers a concussion while still symptomatic from a previous concussion;
- SIS carries a 50% mortality rate, 100% morbidity rate (in animal models).

Question 24

Chronic Traumatic Encephalopathy

Answer 24

Chronic Traumatic Encephalopathy (CTE, aka dementia pugilistica) is the result of multiple, sub-concussive blows to the head.
This is not a concussion issue.
CTE is a progressive degenerative disease found in individuals with repeated head trauma (e.g. boxers, football players, hockey players, etc.).
Characterized by neurofibrillary tangles, plaques and neuronal death.