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Flashcards in Neuroinflammation in Alcohol Dependence Deck (44)
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1

Define inflammation

A reaction to an injury involving the recruitment of cells, heat, redness, and swelling, and accompanied by loss of function and pain

2

Describe the difference between neuroinflammation and inflammation

Neuroinflammation doesn't involve pain (no CNS pain receptors) or redness, and rarely involves heat - although it does involve broader temperature dysregulation.

3

Name the 2 cells which play the greatest role in neuroinflammation

Astrocytes and microglia

4

What are microglia?

CNS macrophages which orchestrate the immune response and release toxic factors, including ROS, prostaglandins, and cytokines (TNF-alpha and IL-1)

5

Name some classic triggers of neuroinflammation

Infectious microbes, autoimmunity, environmental toxins, disease proteins

6

Name some neurogenic triggers of neuroinflamamtion

Enhanced neural activity - noxious stimuli, psychological stress, epileptic seizures

7

Describe some positive responses to neuroinflammation

Homeostatic responses (release of gliotransmitters, neurotrophic factors, and cytokines, vasodilation, phagocytosis) and anti-inflammatory responses (release of anti-inflammatory molecules, vasodilation)

8

Describe some negative responses to neuroinflammation

Maladaptive responses (release of pro-inflammatory factors, plasma extravasation) and neurotoxic responses (release of pro-inflammatory factors, excitotoxicity, apoptosis, BBB breakdown)

9

State the consequences of homeostatic responses to neuroinflammation

Adaptation: microbe elimination, synaptic plasticity, enhanced perfusion, neuroprotection, repair, and regeneration

10

State the consequences of anti-inflammatory responses to neuroinflammation

Termination of the inflammatory response

11

State the consequences of maladaptive responses to neuroinflammation

Dysfunction: hyperexcitability, impaired inhibition, reduced computational power

12

State the consequences of neurotoxic responses to neuroinflammation

Degeneration: progressive loss of CNS function and chronic disease

13

Based on NICE's 2011 figures, what percentage of the UK's population consumes alcohol in a harmful way, and what percentage are dependent?

Harmful use: 25%
Dependent: 5%

14

What percentage of all deaths globally are directly attributable to alcohol? (WHO, 2014)

6%

15

As of 2016, what are the UK guidelines on alcohol consumption?

Weekly limit of 14 units with at least 2 alcohol free days

16

Define hazardous drinking

Drinking resulting in raised physiological observations (e.g. BP) increasing the likelihood of a problem occurring

17

Define problem drinking

Evidence of harmful consequences from alcohol consumption, either physical, psychological, or social

18

Define dependent drinking

3 or more of the following in the last 12 months:
- Craving or compulsion to drink
- Withdrawal symptoms
- Continuing in spite of harm
- Tolerance
- Neglect of other interests
- Difficulty controlling use

19

Describe the effects of alcohol on the brain

General brain atrophy, enlargement of the ventricles, narrow gyri, widened sulci

20

What percentage of the UK population has subtle cognitive dysfunction due to alcohol consumption?

1.5%

21

State at least 4 factors involved in alcohol-related brain damage

Thiamine deficiency, direct neurotoxicity, alcoholic liver disease, multiple withdrawal episodes, TBI, microvascular disease

22

How does alcoholic liver disease contribute to brain damage?

Inflammatory cells cross the blood-brain barrier

23

Describe the parts of the brain affected in alcoholic neuroinflammation

Caudate, putamen, thalamus, amygdala, hippocampus

24

Describe the effect of alcohol dependence on the brains of rats (Syapin, 1998; Oberniew, 2002)

It activates microglia, with microglia remaining activated for at least 14 days after the last alcohol dose. It also stimulates toll-like receptors - especially toll-like receptors 4 and 2

25

Which mice are protected against alcohol-induced cytokine and chemokine release?

Toll-like receptor 2&4 knockout mice

26

In the post-mortem brains of alcoholics, where is monocyte chemoattractant protein 1 (MCP-1) increased? (He & Crews, 2008)

Ventral tegmental area, substantia nigra, amygdala, hippocampus

27

How is chronic alcohol intake associated with pre-clinical inflammation?

Alcohol activates microglia via toll-like receptor 4. Over time, this produces increases in pro-inflammatory cytokines in the brain which persist

28

Name at least 3 ways in which peripheral circulating cytokines reach the brain

Dedicated transporters, the vagus nerve, stimulation of macrophages, diffusion

29

How do peripheral circulating cytokines cause 'sickness behaviour'? (Harrison, 2009)

They enter the brain via various mechanisms and increase activity in the subgenual anterior cingulate cortex

30

How could peripheral inflammation cause memory dysfunction in chronic alcoholism, and give a piece of evidence?

By producing a pro-inflammatory environment in the brain. Peripheral inflammation and high TNF-alpha in AD patients is associated with deterioration in cognition