Epilepsy

Question 1

epilepsy defintion

Answer 1

enduring predisposition so seizures
biol., cog., psych. and social consequences
two unprovoked seizures at least 24 hours apart

Question 2

epilepsy syndrome definition

Answer 2

one unprovoked seizure and probability of >60% of reoccurence
based on family history, ruling out other conditions

Question 3

status epileptica

Answer 3

seizures lasting hours to days to months

Question 4

SUDEP

Answer 4

sudden unexplained death in epilepsy
probably something with brain stem

Question 5

proportion pharmacoresistant epileptics

Answer 5

one third

Question 6

epilepsy brain consequences

Answer 6

neuronal loss
unwanted neurogenesis
axonal and glial changes
BBB changes

Question 7

animal epilepsy models

Answer 7

pharmacological by chemokines -> inflammation
electrode implantation -> status epileptica

Question 8

epilepsy phases

Answer 8

acute phase
latent phase
chronic phase

Question 9

microRNA

Answer 9

small
around 22 nucleotides
non-coding
binds to messenger RNA
fine-tune protein output
can stabilize and destabilise
silencing genes
by binding to mRNA

Question 10

miRNA location

Answer 10

produced in nucleus
transported by exporting 5
cleaved into single strand by dicer
swimming around in cytoplasm

Question 11

miRNA in epilepsy

Answer 11

affecting immune and inflammatory responses

Question 12

sterile damage

Answer 12

damage originating from the brain itself

Question 13

inflammatory responses in the brain

Answer 13

leaky BBB
glial activation
mitochondrial dysfunction
demyeliniation

Question 14

astrocytes as epilepsy model

Answer 14

tissue from surgery
induction of inflammation through IL-1 beta
binding to astrocytes
producing IL-1beta and COX-2
upregulates miRNA146a

Question 15

miRNA146a

Answer 15

mimics cell’s own miRNA
decreases IL-beta and Cox-2 secretion
-> anti-inflammatory

Question 16

miRNA21

Answer 16

no effect
control miRNA

Question 17

miRNA155

Answer 17

increases IL-1beta and Cox-2
-> inflammatory

Question 18

miRNA147b

Answer 18

decreases IL-1beta
-> anti-inflammatory

Question 19

anti-inflammatory miRNA as treatment

Answer 19

miRNA146a and 147b
reduces astrocyte proliferation
promotes neuronal differentiation
-> stem cells develop into neurons, not glia
-> less gloss

146a affects gene transcription through AP-1 and NFkB

Question 20

miRNA in epilepsy phases

Answer 20

miRNA21 unregulated in all phases
miRNA146a, 147b and 155 highest in acute, lowest in latent
-> latent might be the window of opportunity

Question 21

first animal model success in epilepsy

Answer 21

blockage of IL1R / TLR4 pathway
suppressing disease progress

Question 22

miRNA134

Answer 22

regulates dendritic spine volume
via Plum2
-> influencing network excitability

Question 23

miRNA135a

Answer 23

regulates excitatory synapse density
via Mef2 pathway
reduces seizures in chronic trials

Question 24

delivery systems for miRNA

Answer 24

liposome
dendrimers
PEI particles
-> all have to be tested in animals again

Question 25

Miravirsen

Answer 25

first miRNA drug
for hepatitis
in the liver
targeting miRNA122
proving the principle of miRNA drugs

Question 26

antisense oligonucleotide therapy

Answer 26

works for Dravet syndrome
caused by SCN1 mutation
reduces seizures and SUDEP in mice

Question 27

miRNA145a

Answer 27

biomarker candidate for epilepsy
leak out of dead cells
in acute phase
there might be different biomarkers for each phase

Question 28

ROC

Answer 28

receiver operation characteristic curve
important in biomarker finding
area under the curve of true positive / false positive
0.5 is random
closer to 1 is better

Question 29

isomiRNAs

Answer 29

variations on miRNAs
nucleotide additions
truncations
elongations