Stroke Flashcards
Hemiparesis
Hemiparesis is weakness or the inability to move on one side of the body
Hemiplegia
Hemiplegia is a condition caused by brain damage or spinal cord injury that leads to paralysis on one side of the body
Ischemic vs. hemorrhagic stroke
No symtom differences but vessel occlusion = ischemic stroke (80-90% of all strokes) and Intracranial bleeding = hemorrhagic stroke (10-20 % of all strokes)
Best therapy for strokes?
Prevention: no smoking, diabetes, low blood pressure etc.
Symptoms of stroke
Hemiparesis and Hemiplegia
Pathophysiology of stroke
Very complex. core components are vascular occlusions, glutamate relates, increase in intercellular Ca2+, free radical production and so on
Current therapies for stroke
Mechanical recanalization up to 24 hours later (destruction/removal or cloth) or Thrombolysis with recombinant t-PA (4.5-6 hours after, disolves cloth)
Limitations of current therapies for stroke
Suitable only for minority of patients
Narrow time window
High intracranial bleeding risk
3R Principle
1) Avoid animal experiments altogether (Replacement)
2) To limit the number of animals (Reduction)
3) their suffering (Refinement) in tests to an absolute minimum.
Craniotomy
A craniotomy is the surgical removal of part of the bone from the skull to expose the brain
Photocoagulation
Photocoagulation takes place by using the laser to create a microscopic burn in the target tissue
Vasogenic edema
Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels
Microsphere
A Microsphere is a small spherical microparticle, with diameters typically ranging from 1 μm to 1000 μm (1 mm)
What types of stroke models exists
In-silico, in-vitro, ex-vivo and (most importantly) in-vitro (Genetically engineered/ mutated animals, Invasive methods in animals, Non-invasive methods for investigations of humans)
An ideal stroke models should:
… mimic the clinical situation
… be highly reproducible, controllable and standardized
… be easily to perform
… not produce side-effects within the brain
… allow physiological monitoring
… allow for analysis before (!) symptoms become visible (first minutes)
… allow for fast and direct access to brain tissue
… be cost effective
…and should be of limited ethical concern!
Intraluminal suture MCAO model
Use filament that is inserted in the CCA until it comes to the middle cerebral artery. One can do it in 5-7 min.
By occluding the middle cerebral artery, the have a highly comparable model for stroke. Advantage: fast to perform, easy access to tissue, we can use CCT stain to see the ischemic tissue.
You can see what mechanical recanalizing can do to the tissue, as it would be re-oxygenized
Pros: Mimics human ischemic stroke; penumbra; reproducible; reperfusion controllable; no craniectomy
Cons: Increased hemorrhage; not for thrombolysis studies
Bederson Score
from 0- 5 on global neurological ability. Test for severe motor deficits in the acute phase. Circling and spinning is considered bad (4), but not as bad a no movement (5)
Craniectomy model
Permanent Distal Middle Cerebral Artery Occlusion (including occlusion of both CCAs). Reduces collateral blood flow and thus consolidates the ischemic damage.
Pros: Long-term survival; visual conformation of success
Cons: Highly invasive; surgical skills needed; affects intracranial pressure
Photothrombosis model
Using Photoactive dye to and using the laser to create a microscopic burn in the target tissue.
Pros: Long-term survival; defined location; reproducible; low invasiveness
Cons: Early Vasogenic edema formation; not good for research in neuroprotective agents
Endothelin-1(ET-1) Model
Injecting a Vasoconstrictive peptide to decrease the circumference of the blood vessel. Leads to a dose dependent ischemic lesion and rapid cerebral blood flow reduction. Reperfusion will occur over hours
Pros: Low mortality; low invasiveness; lesions in cortical/subcortical regions
Cons: Duration of ischemia is not controllable; induction of axonal sprouting and astrocytosis, which can lead to biases
Embolic Stroke model
Inserting a microsphere or a thromboembolic clot to mimic a blood-clot. Pros: Mimics human pathogenesis best; appropriate to study thrombolysis
Cons: Spontaneous recanalization; High variability of lesion size
Analysis of experimental stroke
Functional outcome
- Behavior tests
Stroke size in the brain (most important)
- MRI/ Histology
Tissue analysis
- Molecular biology (PCR, qPCR)
- Protein analysis (Western blot, ELISA)
- Histology
- Flow Cytometry (Cells/Cytokines)
- Injection of tracersGrip Test
tests motor function, coordination and movement. Scored from 0-5.
