BBB & Fluid Homeostasis Flashcards
What are the causes of brain oedema?
- severe salt & H2O imbalances in blood (hyponatremia)
- brain tumours
- traumatic head injury & stroke
What is hyponatremia?
Na levels in blood abnormally low! (<135mM)
[@ lvls <120mM, condition is known as WATER INTOXICATION]
What does severe hyponatremia cause?
Drives osmotic movement of H2O from blood into brain
What condition can brain tumours cause (in relation to BBB)?
PERITUMORAL OEDEMA
-tumour & surrounding edema can cause neurological symptoms by compressing brain tissue!
What are the FOCAL symptoms of peritumoral oedema?
Neurological!
- muscle weakness
- visual field defects
- aphasia
What are the GENERALISED symptoms of peritumoral oedema?
INCREASED INTRACRANIAL P
- headache
- nausea
- vom.
- cognitive or behavioural abnormalities
What are some treatments of brain tumours (peritumoral oedema)?
- Glucocorticoids (e.g. dexamethasone)
- Surgery
- Radiation therapy
What are various treatments for brain oedema caused by tramatic head injury & stroke?
-Thrombolysis “clot-busting” drugs
(limited use <3h)
-Neuroprotection by HYPOTHERMIA
(Ca channel block)
-Decreased cerebral oedema in large strokes by INTUBATION & HYPERVENT. (increase blood PO2) & mannitol can be life saving!
–CRITICAL WINDOW FOR THERAPEUTIC INTERVENTION!!!!–
What happened to the AQP4 knockout mouse?
DECREASED oedema & neurological deficits after ischemic stroke
Explain the outcome that AQP4 could have to be useful in treating stages of brain oedema?
Early ANTAGONIST (e.g. AqB013):
-block H2O entry into brain
Later AGONIST (e.q. AqF026):
-Increase H2O exit from brain
Give one example of a way you could test for AQP blockers.
OSMOTIC SWELLING
- no block = oocyte swells and bursts
- effective blocker = normal round oocyte
What function fo AQPs have in cancers?
INCREASE migration & metastasis!
What are glioblastomas related to?
The upregulation of AQP1
