Neurology Flashcards
Define ‘sustained threat’
An aversive emotional state caused by prolonged (i.e., weeks to months) exposure to internal and/or external condition(s), state(s), or stimuli that are adaptive to escape or avoid.
Define ‘pathophysiology’
The disordered physiological processes associated with disease or injury.
Define ‘allostatic load’
“the wear and tear on the body” which accumulates as an individual is exposed to repeated or chronic stress.
Define ‘functional connectivity’
the temporal coincidence of spatially distant neurophysiological events
Are placebos efficacious in the treatment of GAD?
The meta-trial says no
Are placebos ethical in the treatment of GAD?
Nocebo:
link neurology to symptoms to definition
Describe the role of glutamate in ASCs
Different ratio of inhibition/excitation - synchronicity
Stats relating GAD and ASCs
- Roughly 40% have symptoms of at least one anxiety disorder at any time, compared with up to 15% in the general population
- anxiety disorders are the most common comorbid conditions in these patients
Define ‘pathogenesis’
the manner of development of a disease
Define neurodegeneration
progressive atrophy and loss of function of neurons
Describe postbiotic bacteriotherapies
target downstream signaling pathways of the microbiome and act by mitigating the negative effects of an excess, scarcity, or dysregulation of metabolites involved in these pathways
Describe propionate pharmacokinesis
Major component of SCFAs
Produced by Clostridia
How did Gertrude Elion prevent vertical HIV transmission
synthesised zidovudine, an antiretroviral nucleoside analogue of thymidine triphosphate, with the hydroxyl group replaced with an azide group - suppression of viral load
Describe the feats of Gertrude Elion
Synthesisinng antimetabolites such as diaminopurine and thioguanine (structural analogs of adenine and guanine) to prevent incorporation of these natural purines, on which bacterial DNA synthesis is dependent
Synthesised 6-mercaptopurine (by substituting an oxygen atom with a sulfur atom on a purine molecule)
Describe the work of Jane Cooke Wright
- research into folic acid antagonists as chemotherapeutics
- pioneered the biopsy
Describe the work of Flossie-Wong Stahl
Researched HIV gene therapy to achieve intracellular immunisation, pursued through HIV-based lentiviral vectors in cell cultures, with the aim of modifying both CD4 cells and red blood cells to have antiviral genes coding for immunotherapeutic features.
Genetic modification was done on hematopoietic stem cells using a hammerhead ribozyme in order to produce HIV-resistant cell progenies, to re-establish a functional immune system and control HIV replication.
Describe the work of Irene Curie
Bombarded elements with α-particles emitted from polonium - emission of positrons and radioisotope of phosphorus, nitrogen and silicon. β-decay overturned the Dalton atomic model of a solid sphere.
Describe the work of Chien Shiung-Wu
Used a cobalt-60 β-source polarized by the demagnetization method.” Using a sample of radioactive cobalt-60 (undergoes β-decay - replacing a neutron with a proton, electron and neutrino) cooled to cryogenic temperatures (needed to reduce thermal vibration of the atoms to almost zero). Constant and uniform magnetic field was applied so that the spin axes of the atomic nuclei lined up in the same direction. The β-particles were emitted asymmetrically along the nuclear spin and opposite to the spin, disproving the law of the conservation of parity for weak nuclear interactions (such as β-decay). This caused re-evaluation of previous assumptions, and developments in quantum theory - an integral step in the development of the Standard Model of particle physics used today.[47]
Describe venom
Cleave the sn-3-glycerophospholipids into fatty acids and lysophospholipids through hydrolysis of the sn-2 acyl ester linkage at the envelope, causing envelope degradation and RNA exposure
Describe termite microbiota
in the hindgut of Macrotermitinae, which host exosymbiotic Termitomyces fungus and gram-negative nitrogenase-positive endosymbiotic mutualistic diazotrophic γ-proteobacteria containing RSN-TKY17 and NKN19 niFh clusters
Describe oxidative stress
One of the types of change found in essentially all neurological degenerative diseases is the over-expression of oxidative free radical compounds that cause lipid, protein and genetic structural changes
Evidence of neurodegeneration in autism
1) significantly decreasing amount of Purkinje cells in the brain
2) neuronal cell loss,
3) activated microglia and astrocytes,
4) proinflammatory cytokines,
5) oxidative stress,
6) elevated 8-oxo-guanosine levels
8-oxo-guanosine
one of the most common DNA lesions resulting from reactive oxygen species modifying guanine
microglia
the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS).
astrocytes
a sub-type of glial cells in the central nervous system - envelop synapses
microglia
- the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS)
- maintain cerebral homeostasis
Describe the vicious cycle of oxidative stress
1) Oxidative stress causes damage to mtDNA
2) Damaged mtDNA leads to decrease in coding for proteins needed for electron transport chain
3) Decreased function of electron transport chain leads to decreased energy and increased free radicals (oxidative stress)
4) Increased oxidative stress causes damage to the cell membrane
5) Damage to the cell membrane leads to release of cytochrome C leading to apoptosis or cell death
6) Cell death leads to more oxidative stress
Describe microglial activation
- Rapid proliferation of microglial cells
- Migrate to site of infection
- M1 activated microglia: neurotoxic with release of pro-inflammatory cytokines
- Engulf dying cells, infectious agents, toxic proteins, and cell debris
List some pro-inflammatory cytokines
TNFalpha, IL-1B, IL-6, COX, Reactive oxygen species (ROS), Nitric oxide
M1 microglia
Responsible for inflammation
Functions of astrocytes
1) Induce formation of neuronal synapses
2) Formation and maintenance of BBB
3) Neurotransmission: component of tripartite synapse model
4) Homeostasis and turnover of glutamate
5) Metabolic regulation
6) Ion balance maintenance
7) Key role in development of the nervous system
Neuroinflammatory markers in ASCs
1) Microglial activation
2) Astrocytic activation with elevated levels of GFAP(glial fibrillary acidic protein)
3) Proinflammatory profile of cytokines in the brain, CSF and blood
4) Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation
Evidence of autoimmunity in autism
accumulation of T cells and astrocytes in postmortem brain tissue
brain blebs may be formed in response to the infiltration of T cells into the space between blood vessels and neural tissue, while the cell fragments they contain could come from the astrocytes that make up the glia limitans
Glia limitans
the final wall of defense separating neural tissue from foreign and toxic substances circulating in the blood
What is the BBB
The blood-brain barrier is a dynamic interface between the peripheral blood supply and the cerebral parenchyma, controlling the transport of material to and from the brain
BBB dysfunction in ASCs - specifics
Perturbation of these processes:
Tight junctions between the endothelial cells of the cerebral microvasculature limit the passage of large, negatively charged molecules via paracellular diffusion.
Transcellular transportation across the endothelial cell is controlled by a number of mechanisms including transporter proteins, endocytosis, and diffusion.
BBB dysfunction in ASCs - basics
Increased permeability of the BBB leading to increased infiltration of peripheral material into the brain culminating in neuroinflammation and oxidative stress.
Microglial role in development
- help to set up the circuits of the brain by strengthening appropriate cell-to-cell connections and by eliminating improper connections in the brain
- regulate the plasticity of brain cells and prune synapses
Gliosis
proliferation or hypertrophy of several different types of glial cells, including astrocytes, microglia, and oligodendrocytes
Clostridia metabolites:
3-(3-hydroxyphenl)-3-hydroxypropionic acid (HPHPA) and 4-cresol
Clostridia metabolite effect
inactivate dopamine beta-hydroxylase, which is needed for the conversion of dopamine to norepinephrine
Nocebo effect
‘symptoms related to the patient’s negative expectations not only in a clinical trial setting, but also in a routine care setting’
GAD - anticipation and neurovegetative signs