The Neurobiology of Concussions Flashcards
What is a concussion?
Also referred to as a Mild Traumatic Brain Injury.
Defined as biomechanically induced transient disturbance of neurological function.
May or may not be associated with loss of consciousness.
Temporary loss of brain function.
Produce a variety of physical, cognitive, and emotional symptoms.
Symptoms subside naturally.
What causes a concussion?
Rapid acceleration and/or deceleration of the brain.
Resulting in brain colliding with skull, both the front and back (or side to side).
Bruising and swelling of brain tissue follows and may persist for up to 48 hours. Brain conclusion and cerebral edema. Increased intracranial pressure.
Impact an be direct or indirect, it doesn’t matter. E.g. sport related collision vs. blast explosion at war.
Impact can be linear, rotational or angular. Direction of force DOES matter.
Why/how does direction matter?
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).
Rotational Forces
The magnitude of rotational force is thought to dictate concussion severity.
Diffuse Axonal Injury: shearing forces cause axons to detach from cell body. Damaged axons display indiscriminate release of the excitatory NT glutamate. Excitotoxic lesions subsequently occur from 24-48 hours post injury.
Parts of the brain most affected are the midbrain and diencephalon. Disruption of normal cellular activities here is thought to produce LOC. Also damages frontal and temporal lobes.
Unrestricted movement of the head results in axon shearing often leading to subdural hematoma -> a 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.
Epidural hematoma results from the collection of blood between the dura mater and the skull.
Acute Metabolic Cascade
A concussion can lead to neural and vascular tissue damage, leading to a distortion of cell membranes.
Neurone activity picks up and cerebral blood flow is interrupted.
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.
Glutamate
Main excitatory NT in the brain. It’s also present in more synapses than any other NT.
Once released into the synaptic cleft, glutamate can bind to three post-synaptic receptors: AMPA, NMDA, and 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.
Glutamate Excitotoxicity
Too much glutamate being released can cause damage to surrounding neurons.
Excitotoxicity can occur with overexposure to glutamate caused by prolonged depolarization of the post-synaptic neuron.
When neurons are subjected to prolonged stimulation by glutamate, a large % of cells die via 1 of 2 mechanisms (Necrosis and Apoptosis).
Glutamate activation of NMDA receptors can, in some cases, allow the entry of calcium 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, and can lead to initiation of apoptosis.
Necrosis
Characterized by rapid lysis of the cell due to osmotic swelling.
Apoptosis
Delayed cascade of biochemical events that leads to DNA breakup and ultimately cell death.
Energy Crisis
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 -> this requires a ton of ATP.
Increased demand for ATP results on massive increase in glucose metabolism.
Increased demand for glucose comes at a time when cerebral blood flow is reduced and mitochondria are dysfunctional.
Hypoglycemia ensues, leading to cognitive deficits and an energy crisis that leads to secondary injuries.
Secondary Injuries - BBB Permeability
Anaerobic glucose metabolism (glycolysis) involves production of lactate - 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.
Secondary Injuries - Inflammation
Following brain injuries, a patient’s 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 just as long.
Clinical Symptoms
They are entirely dependent on the location of structural damage.
A patient may experience:
Headache, pressure in the head (vascular injuries).
Temporary loss of consciousness (brain stem).
Confusion (corpus collosum).
Amnesia surrounding the event (hippocampus, frontal lobes).
Ringing in the ears (temporal loves).
Nausea and/or vomiting (area postrema).
Changes in mood and emotional disturbances (amygdala).
What are the three methods of detection and diagnosis?
Immediate Post Concussion and Cognitive Testing, MRI, and EEG.
Immediate Post Concussion and Cognitive Testing
Computer-based battery of tests aimed at detecting post -concussive symptoms, demographic questionnaire, symptom inventory, injury evaluation, and 20-minute neurocognitive test.
