Epilepsy

Question 1

Acquired epilepsy is frequently associated with

Answer 1

structural lesions after trauma, stroke, and infections

Question 2

At the time of insult, there are acute processes such as

Answer 2

mitochondrial dysfunction and damage to the blood-brain barrier (BBB) that lead to transcriptional events and altered signaling which promotes Epileptogenesis

Question 3

Over weeks (after insult)

Answer 3

these changes manifest into alterations of circuit activity that results in the potentiation of spontaneous seizures

Question 4

Reduction in mitochondrial redox status leads to

Answer 4

1. irreversible oxidation
2. mtDNA damage
3. the failure of mitochondrial repair
4. decreased oxidative phosphorylation
5. ATP production by mitochondria

Question 5

Antioxidants can scavenge ROS or increase the ability to

Answer 5

neutralize ROS by inducing the expression of genes involved in cellular protection

Question 6

Slow releasing MMF’s

Answer 6

diroximel fumarate, tepilamide fumarate and chemically linked conjugates of MMF

Question 7

What is MiR-134?

Answer 7

a brain-specific, activity-regulated miRNA that has been implicated in the control of structural neuroplasticity of spines via the Limk1/cofiling signaling pathway.

Question 8

What did silencing MiR-134 with antagomirs do?

Answer 8

Silencing miR-134 in mice using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus (Mateos et al.,2012)

Question 9

What did depletion of MiR-134 after SE do?

Answer 9

Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy

Question 10

What does extravasation of serum albumin into the cerebral cortex microenvironment do?

Answer 10

activates a transforming growth factor-β receptor (TGFβR)-mediated signalling cascade in astrocytes and causes local inflammation

Question 11

What does blocking TGFbeta signalling do and who showed this?

Answer 11

Blockade of TGFβ signalling in the albumin model of epileptogenesis reversed inflammation and transcriptional patterns associated with activated glia and prevented the development of epileptiform activity (Cacheaux et al., 2009)

Question 12

In what models did Losartan block seizure development?

Answer 12

after exposure to albumin and after vascular injury in rats (Bar-Klein et al.,2014)

Question 13

LOF mutations upstream of mTOR have been associated with

Answer 13

CNS disorders

Question 14

Clinical use of rapaymycin - year and author

Answer 14

Bebin, 2013

Question 15

Everolismus - year and author

Answer 15

Ryther, 2012

Question 16

What does NKCC1 expression change do?

Answer 16

shift from hyperpolarizing to depolarizing GABA currents in adult neurons, which may crucially contribute to the chronic hyperexcitability of epileptic neurons

Question 17

In what two places has bumetadine been shown to suppress depolarizing GABA currents?

Answer 17

subicular pyramidal cells (Huberfeld et al., 2007) and reduce seizure frequency in patients with temporal lobe epilepsy (Eftekhari et al., 2013

Question 18

Who rearranged GABA and glutamate receptors?

Answer 18

Haberman et al., 2002; Raol et al., 2006

Question 19

Who showed that GABA/GluR reconfiguration was dependent on population?

Answer 19

Marks et al., 2008

Question 20

Where was Kv1.1 overexpressed and by who?

Answer 20

lentivirus vector-mediated overexpression of the potassium channel Kv1.1 preferentially in excitatory neurons, which reduced neuronal excitability, suppressed seizures in a rodent model of neocortical epilepsy (Wykes et al.,2012)