CNS Response to Injury Flashcards
Occurs when a sudden trauma causes damage to the brain
-Can result when the head suddenly and violently hits an object, or when an object pierces the skull and enters brain tissue
Traumatic Brain Injury (TBI)
When the brain slides forward and hits the frontal bone then backwards and hits the parietal bone
Coup-Contrecoup
Contrecoup contusions are more frequent than coup contusions in
Falls
Diffuse axonal injury can be seen histologically with
Beta Amyloid Precursor Protein (BAPP)
Associated with inflammation, gliosis & other pathological responses
TBI
The injury site is invaded by astrocytes, forming a
Glial Scar
A long-term problem of CNS injury is
Inflammation
Repeated sports-related head injuries results in concentrations of
Hyper p-tau protein (dark regions)
Hyper p-tau protein concentrations cause
Chronic Traumatic Encephalopahty (CTE)
Results in regional cerebral atrophy and can cause cavum septum pellucidum
CTE
We can see chronic neurodegeneration after a
TBI
A rapid blockage of a cerebral artery
Ischemic Stroke
Bursting of a vessel
Hemorrhagic stroke
Characterized by sudden numbness or weakness, especially on one side of the body
- Sudden confusion or trouble speaking or understanding speech
- Sudden trouble seeing in one or both eyes
Stroke
Both cause cell death due to lack of oxygen and production excytotoxins and free radicals
CNS stroke and Severe TBI
Excessive activation of neuronal glutamate receptors by a group of L-glutamate analogs results in
Neuronal Damage
Any chemical possessing unpaired electrons
-In biological system these are oxygen radicals
Free radicals
Causes loss of muscle and negative nitrogen balance, decreased gluconeogenesis, osteoporosis, increased hepatic lipogenesis, increased lipolysis in adipose tissue, decreased lipoprotein lipase activity in muscle and adipose tissue, cachexia
Chronic inflammation
Anemia of chronic disease, leukocytosis (high white blood cell counts), thrombocytosis (high platelet counts)
Hematopoetic changes in chronic inflammation
What do we use to manage the inflammatory response of spinal cord injury?
Methylprednisolone, Erythropoetin, and Minocycline
Causes tissue disruption and primary cells death
Spinal Cord Injury (SCI)
Injured spinal cords show progressive
Tissue loss
With an SCI, central hemorrhage necrosis develops over
2-3 hours
With an SCI, white matter blood flow falls by
50% within 3 hours
Metabolism is compromised with high lactic acid levels with an
SCI
Intracellular calcium activity >1µM activates proteases and phospholipases, breaking down proteins and lipids with an
SCI
This calcium then binds to mitochondria and produces
Free radicals
After injury, we begin to see neuronal apoptosis in the gray matter surrounding the injury. This peaks at
48 hours
We also see oligodendroglial apoptosis after injury in white matter tracts. This peaks
10-14 days after injury
We see breakdown of the blood brain barrier and rapid pro-inflammatory cytokine response (<1 h) with
SCI
Distal to the SCI lesion, we see
Wallerian degeneration
Severed spinal cord axons fail to
Regenerate
We get axonal degeneration and loss of myelin where?
Distal to an SCI injury
Disrupt axon extension in CNS injury
Inhibitory factors
We get a growth cone and axon growth-promotoing signals with
PNS injury
Can regenerate
PNS axons
Can induce central axons to regenerate
Sciatic nerve grafts
May be capable of regenerating given the appropriate environment
Central axons
Block regeneration
Glial scars
What are 4 exampls of inhibitory factors in the glial scar?
Myelin basic protein, Nogo A, MG, and OMgp
Inhibits growth of CNS axons
Nogo
Leads to long-distance regeneration and functional recovery in rats treated with anti-antibodies
Deactivation of Nogo A
What are three commonly used cell types to attempt to regenerate CNS axons after SCI?
OECs, Schwann cells, Neural Stem calls, and Embryonic stem cells
We can use human embryonic stem cells to derive
Oligodendrocyte precursor cells
We also can see axon emergence from grafts with human
Neuroprogenitor Cells (NPCs)
Can induce central axons to regenerate
Sciatic nerve grafts