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Flashcards in Neuroinflammation in Alcohol Dependence Deck (44)
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Define inflammation

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


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.


Name the 2 cells which play the greatest role in neuroinflammation

Astrocytes and microglia


What are microglia?

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


Name some classic triggers of neuroinflammation

Infectious microbes, autoimmunity, environmental toxins, disease proteins


Name some neurogenic triggers of neuroinflamamtion

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


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)


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)


State the consequences of homeostatic responses to neuroinflammation

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


State the consequences of anti-inflammatory responses to neuroinflammation

Termination of the inflammatory response


State the consequences of maladaptive responses to neuroinflammation

Dysfunction: hyperexcitability, impaired inhibition, reduced computational power


State the consequences of neurotoxic responses to neuroinflammation

Degeneration: progressive loss of CNS function and chronic disease


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%


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



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

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


Define hazardous drinking

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


Define problem drinking

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


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


Describe the effects of alcohol on the brain

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


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



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

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


How does alcoholic liver disease contribute to brain damage?

Inflammatory cells cross the blood-brain barrier


Describe the parts of the brain affected in alcoholic neuroinflammation

Caudate, putamen, thalamus, amygdala, hippocampus


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


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

Toll-like receptor 2&4 knockout mice


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


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


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

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


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


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