Regeneration and Sleep Cycle Flashcards
(44 cards)
What is a glial scar?
Hypertrophic glial proliferation (microglia, reactive astrocyte, oligodendrocytes) at the site of lesion which prevents axons from growing across the lesion to innervate distal targets (principally resulting from astrocyte proliferation, only 0.5-2mm)
There is prolonged debris removal from Wallerian degeneration in the CNS compared to PNS
List some inhibitory factors released by the glia:
Inhibitory factors produced by glia:
- Nogo-A (fraction of CNS myelin)
- Chondroitin sulfate proteoglycan (ECM from Astro)
- MAG (Oligo)
- Sema4D (Oligo, trophic factor)
- Ephrin B3
What is a major problem in CNS regeneration?
Caspase mediated apoptosis – commonly resulting from glutamate excitotoxicity (upregulate NMDA receptors) or excessive cytokine stimulation
What does the influx of calcium do in CNS damage / regeneration?
Calcium influx also facilitates a “wash out” of the axonal contents (neurofilaments and microtubules), mitochondrial dysfunction, protease activation –> cytoskeletal damage & chromatolysis –> impeding regeneration via killing the neurons
No good for regeneration.
What is the largest hindrance for spinal cord injury recovery?
Dorsal Root Entry Zone - because of the proliferated astrocytes (glial scar) and produced inhibitory trophic factors at this CNS/PNS border
What is Wallerian Degeneration?
Degradation of the distal axon following transection of the axon (both CNS and PNS), however the basil lamina tube (Bands of Bungner) containing Schwann/oligodendrocyte cells remains providing a structure for the regrowth of the axon following growth cone formation
In the PNS there is also secondary proliferation of Schwann cells (confined by basil lamina)
How is PNS recovery ordered?
First: pressure and crude tough sensation return (Protopathic)
Second: fine touch and fine motor return (could not return) (Epicritic)
- Physical therapy of the affected region has been shown to increase the chance and rate of recovery via increased trophic support
Does method of damage affect recovery potential?
Yes! Recovery of crushed neurons is MUCH more efficient than those sectioned
Axonotmesis: compression injury
Neurotmesis: severing injury
How does stem cell replacement work in regeneration?
Neuron stem cells are supplied from olfactory receptors, taste buds, dentate gyrus of hippocampus (granule cells)
- regeneration occurs but INSUFFICIENT numbers to facilitate functional circuitry :(
Why does a neuroma form?
When the axon attempts to regrow (usually from neurotmesis), it fails to enter a band of Bungner (tube of Schwann cells) and the new nerve ends blindly in tissue; similar situation when axons attempt to cross a glial scar
–> phantom pain
How are neuromas treated?
Treatment involves cutting the end with the neuroma to attempt to initiate functional regrowth across the lesion
What role to CNS cysts play in regeneration?
Cyst formation at the site of the lesion, as in central cavitation, further impedes regeneration
What is reactive synaptogenesis? (collateral sprouting)
Functional method of recovery such that a transected axon that didn’t recover would have an adjacent neuron overgrow into the transected neurons territory of original innervation (also mildly occurs within the CNS)
What is the goal of PNS to CNS grafting experiments?
Hypothetically, allows for CNS neurons to grow from CNS to PNS and then back to CNS (bypassing the initial glial scar and inhibitory factors
- however, once encountering the PNS:CNS barrier the axons did not successfully reinnervate targets
DOESN’T WORK
Pharmacological therapy for regeneration?
- Steroids for antioxidant and anti-inflammatory action
- NMDA antagonists
Causes for ending of the critical period in regeneration?
- plasticity decreases when axonal growth ceases
- synaptic transmission matures
- cortical activation is constrained
What nucleus is the major trigger for sleep via GABA-ergic projection to the tubulomammillary nucleus (TMN)?
Ventral Lateral Preoptic Nucleus (VLPO) of hypothalamus
What does the tubulomammillary nucleus (TMN) do?
Tonically produces histamine for wake state
How do GABA-ergic circuits in the pons also promote sleep (in addition to VLPO)?
Ach inputs to GABA-ergic thalamic neurons
What do orexin neurons in the lateral hypothalamus do?
Stimulate:
- tubulomammillary nucleus to increase histamine production (during sleep) to initiate wakefulness
- brainstem nuclei (Raphe nuclei (5-HT), Locus coeruleus & LTA (NE)) to initiate arousal
List input to the cholinergic nuclei:
- Laterodorsal tegmental nucleus and pedunculopontine nucleus
- Nucleus basalis
- Nucleus of diagonal band
- Medial septal nuclei for initiation of REM
What is narcolepsy and what causes it?
- Lesion to orexin neurons or deficiency of hypocretin will lead to lack of waking stimulus
- (REM sleep attacks) causing excessive daytime sleepiness, cataplexy (sudden REM paralysis, hypnagogic hallucinations (graphic dreams), sleep paralysis
- seen in 1/1000 in US (genetic)
What will a lesion to the VLPO cause?
Insomnia due to lack of GABA-ergic input to TMN
What is an electroencephalogram of sleep?
Recording of the underlying neuronal activity within the cortex
- Synchronous activity is REQUIRED for good recording of the activity and this is seen in the deep sleep stages when synchrony is at its highest
Magnetoencephalography (MEG) is also a method of cortical activity recording
