KNES 505 - 3. Blood-Based Biomarkers

can concussion be seen on MRI and CT scans of the brain?

rarely, typically no

define mild TBI

a rapid onset neuronal dysfunction that often resolves in a spontaneous manner over a few days to weeks

- "diffuse" in brain meaning injury goes through the brain

what is one of the most studied areas of head impacts? what is commonly used? what does it assess in terms of head impacts?

the automotive industry

- commonly use crash test dummies to detect head impact

- assesses linear and rotational data along x, y, and z axis

when a concussion occurs the brain commonly experiences what 2 forces?

linear and rotational forces

the brain is more sensitive to which force?

rotational

- especially in sport

what happens to brain tissue when rotational force is experienced?

deforms with the shear forces associated with rotational acceleration throughout the brain

- therefore have high potential to cause greater tissue damage

what is the most delicate part of neuron?

axon

when brain rotates we are shearing ___________

axons

shearing occurs between white and grey matter because...

each matter has different densities

tissue of the brain can withstand back and forth _______ movement BUT _________ is not as robust

linear, rotational

T of F - it is rare cells die from concussion

true

- if did would be a large TBI

brain membrane cannot be conductive unless..

unless there is an unequal distribution of ions to create an action potential

describe the neurometabolic cascade that occurs as the neurons are streched

a) potassium leaks out of neurons creating increased demand for glucose (need NRG)

b) calcium leaks to promote vasoconstriction in the cerebrovascular (blood supply at glucose site goes down)

c) overall causes decreased efficiency in brain function --> recognized as clinical symptoms (e.g. headaches, concentration problems, etc.)

the ionic influx of potassium causes an indiscriminate release of what?

glutamate

what is glutamate?

powerful neurotransmitter in the brain for cell signaling

if to much glutamate is released there an increased risk of ___________ occurring?

risk of seizures occurring

excess glutamate can trigger ligan gated and voltage channels in the brain to _____________ and disrupt normal responses

depolarize

to restore ionic homeostasis after a neurometabolic cascade there is a depletion of what 2 things?

- intracellular energy reserves

- calcium

--> causes decreased metabolism and challenges to neurovascular coupling

what are the two markers related to neuroinflammation following a concussion?

2 cytokines

- interleukin (IL)

- tumor necrosis factor (TNF)

what is one of the benefits of examining biomarkers?

they are an objective tool which are not influenced by individual expectations

it is thought that one of the main causes of clinical symptoms may be related to what type of injury? what is it caused by?

axonal injuries caused by acceleration or deceleration and or rotational forces on brain tissues

- result in rapid stretching of axons

what are the three biomarkers for axonal injury discussed in class?

1. tau

2. neurofilament light (NFL)

3. neurofilament heavy (NFH)

myelin basic protein (MBP) is a candidate biomarker for _____________ ________________ integrity?

white matter integrity

what are the 2 biomarkers that show enrichment in the neuronal soma?

1. neuron-specific enolase (NSE)

2. ubiquitin C-terminal hydrolase

astrocytes are largely associated w/ what response?

neuroinflammatory response

astrocytes and microglia that were active during concussion thought to secrete what 2 biomarkers?

secrete:

- s100B

- glial fibrillary acidic protein (GFAB)

in testing between UCH-L1 and GFAB which one was said to be more sensitive? issues?

UCH-L1 levels higher especially in youth

- this means this biomarker could just be sensitive to subtle impacts or not entirely specific to the brain

Research from Ann Mckee's group in Bostin have suggested that chronic exposure to concussive (and sub-concussive) impacts may lead to neurodegenerative diseases such as what?

Chronic Traumatic Encephalopathy (CTE)