Flashcards in Neuroinflammation in Alcohol Dependence Deck (44)
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%
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
- 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