Glial.txt

Maintain environment, blood flow (nutrition), signal interaction and respond to injury or disease.

Oligodendrocytes die, lose myelin, axons and function

• Resident CNS macrophages(marrow origin)
• Express CD45=leukocyte common antigen
• Tile CNS contiguously
• Motlile

• Protoplasmic (gray matter)
• Fibrous(white matter)

• Support
• Maintain environment (K+, H2O, transmitter uptake), blood flow (cerebral vessels)
• Blood brain barrier
• Energy metabolites
• Synapse plasticity, activity and number
• Injury

• Near synapse
• Uptake: H2O, K+, glutamate, GABA, glycine
• Release: gliotransmitters (ATP, glutameate)
• Influence synapse formation & plasticity (thrombspondin)

Fills space between neurons with dendritic branches & synapses& support glia

• No action potentials
• Increase cytoplasmic calcium in response to synaptically release glutamate or GABA
• Release gliotransmitters like D-serine: affect synaptic function
• Adenosine is implicated as a mediator of certain deep brain stimulus (Parkinson’s)
• Can be blocked by TTX (synapse activity)

• Uptake glucose from BV and process into substrates for axons(lactate)
• Release factors that vasoconstrict or dialate
• Vascoconstrict: Arachidonic acid
• Vasodialate: Prostaglandin E2 (PGE2) & NO
• Responsible for measureable fMRI scan changes of CNS function

End feet envelope CNS vessels at tight junction (NOT fenestrations) of capillary endothelial

• Prevents charged molecules crossing (NH4+
• Allow: lipid soluble

• Non-cell autonomous neuronal degeneration of cerebellar Purkinje neurons and granule neurons.
• Dicer: endonuclease indispensible for biogenesis of small regulatory RNAs (miRNAs)

• Glial response to CNS insults/injury (get bigger first then proliferate if necessary)
• Glia(microglia & astrocytes) are main responders to disease and play major roles in determining clinical outcome

• Mediate inflammation of all forms of insult (infection, ischemia, injury, degeneration)
• Hypertrophy-> transform to macrophage-> proliferate
• Phagocytose debris & produce chemokines, cytokines and growth factors
• Attract leukocytes & activate astrocytes
• Directly effect neuronal function
• Target of HIV in NeuroAIDS & cause symptoms

• Astrocyte response to all forms of injury
• Change in gene expression(molecular changes)->function
• Hypertrophy yet non-overlapping domains preserved in mild & moderate
• Sometimes scarring (severe cases): overlapping astrocytes loss of ind domains along borders to damage
• Intensity varies with severity
• Specific molecular signaling mechanisms

GFAP: glial fibrillary acidic protein

• GFAP+
• Preserved domains
• Little/no proliferation
• Effects on synaptic function (unptake K+, H2O, glutamate, regulate blood, energy, gliotransmitters)
• Cytokines: modulate glutamate signaling increase AMPA & NMDA receptors in dentritic spine post synaptic cells

Neuronal vulnerability to excitotoxicity

• Chronic pain: from chronic stimulation changes gene expression and functional changes that influence local neurons and alter sensitivity.
• Some new meds may influence glia rather than neurons to manage pain

• Ischemia->lack of ATP -> no glutamate uptake in astrocyte->ATPase pumps fail and even more glutamate may be released from astrocyte
• Extracellular glutamate-> excitotoxic cell death of neurons via NMDA receptor over activation (especially in hippocampus (memory))
• NMDA glutamate receptor overactivation: leads to excess Ca2+ signaling and excitotoxic cell death

• Prevents spread of inflammatory cells/signals (gFAP and CD45)into healthy tissue
• Contributes to failure of axon regeneration due to shared migration cues

Form barriers around vessels to restrict entry of inflammatory cells and microbes during CNS infections and autoimmune inflammation.

• CNS autoimmune disease where autoAb selectively attack & damage astrocytes
• NMO-IgG binds to AQP4 exclusive to astrocytes
• Causes inflammatory cell lesions in the CNS and severe regions of demyelination in optic nerves& spinal cord & recurrent attacks of blindness and paralysis.

• Change in gene expression, hypertrophy, function, scars.
• Why? Regulate inflammation, protect neurons & modulate pain.

• Loss of normal function: glutamate uptake, inflammation reg, energy provision, vascular reg, homeostatis, synaps
• Gain of detrimental effects: cytokines and growth factors that alter neuronal, neurotoxicity (NO, ROS, glutamate)
• Loss or changes can precipitate non-cell autonomous neuronal degeneration (astrocytopahties)

• Astrocyte like: reactive
• BUT they promote the regeneration of damaged axons (growth cones)not like astrocytes

• Wallerian degeneration before axon regeneration
• (1-4) myelin degenerates & macrophages phagocytose debris
• (5-7) Schwann cells become reactive & multiply to fill endoneurial space, secrete ECM and GFs

An unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage.

• Dr. Horrace Wells from Professor Colton who demonstrated N2O, in 1845 demonstrated N2O extraction
• Dr. Morton was first anesthesia specialist

• Accurate assessment, methodical prevention & aggressive treatment
• Assessment: medical Hx, listen, self-report quantitative, scales.

• Acute: Obvious value to organism: impending or actual tissue injury
• Post-operative: (inflammatory component) Cox-2 and opiods
• Chronic: variable etiology (arthritis, migrane) persists after initial injury, no obvious survival value

• May involve TMJ (55% affected, 70% radiographic TMJ involvement)
• Juvenile form may lead to retrognathia

• A and C fibers lose Na+ channels so that acute nociceptive pain sensation is lost.
• (could be reversed -> hypersensitivity)

• Nociceptors: thin diameter primary afferent fibers
• Primarily A-delta and C fibers

• Enamel: none
• DEJ: pain
• Dentin: pain
• Pulp: pain
• PDL: touch, warm, cold, pain

• Puff->pain
• Drying-> less puff pain
• Dry filter paper-> pain
• Filter paper w/isotonic KCl-> NO PAIN
• Conclusion: pain due to displacement of nerves in predentin & pulp by movement of tubular fluid
• Nerve fibers reach only about 100 um into tubules therefore are only activated by fluid displacement

• NH4+, AA, lactic acid or sucrose in dentinal cavity produced nerve impulses
• Prostaglanding E2 and F2 alpha had about 20x regular levels in painful teeth.
• Inflammatory pain: damaged tissue, immunocompetent and tumor cells release chemicals that activate and/or sensitize nociceptors, which in turn results in sensitization of CNS neurons.
• Histamine, serotonin, bradykinin, prostaglandins, ATP, H+, NGF, TNF-a, enothelins, interluekins
• Treatment options: COX2 inhibitors, opiods

• Charateristic of nociceptors that increases number of impulses elicited by successive stimuli at a reduced threshold.
• Initiates or increases ongoing activity.
• Involves arachidonic acid metabolites (PGs, leukotrienes)
• Other innocuous primary afferents don’t sensitize, they adapt.

• Mechanisms through which sensitization of primary afferents
• Polymodality:
• Modifiability:
• Sensitization:

• C and A-delta fibers do not just convey pain to CNS
• Generates and action potential in the collateral fibers to release neurotransmitters (neuropeptides) that activate immune competent cells, increase collagen synthesis, regulate gene expression
• Substace P-> vaso and immune effects

Vasodilation, plasma extravasion, smooth muscle contraction, mitogenesis, collagen formation, modulates leukocytes, arachidonic acid metabolism (PGs release) and maintains mineralized tissue.

They become friable or brittle because nerves provide nutrients and help maintain mineralized tissue.

• Early: involes neuropeptides, glutamatergic receptors and substance P receptors
• Delayed (minutes, hours, days until repair) Prostaglandins
• Prostaglandins involved with both peripheral and central sensitization, that is why aspirin and ibuprofen are effective analgesics.

• Characterized by nerologic defecits and chronic pain
• Treatment options: tricyclic antidepressants, anticonvulsants, Na+ channel blockers, NMDA receptor antagonists, opiods