Neurophysiology & Neurotoxicology

Neurophysiology
Growth hormone
release is stimulated by:
exercise
sleep
insulin hypoglycaemia
CLONIDINE
arginine
GLUCAGON
DESIPRAMINE
Prolactin
causes of elevated prolactin include:
1. Normal states:
stress
pregnancy
lactation
2. Drugs:
D2 antagonists
oestrogens
TRH
dopamine depleting drugs, e.g. RESERPINE, METHYLDOPA
3. Other:
pituitary tumour (prolactinoma) -- prolactin usually > 4000 mU/L
renal failure
post-herpes zoster
chest wall reflex (e.g. nipple stimulation)
epileptic seizure
ECT
Neurophysiological measures
Event-related potentials
occur on the EEG in response to specific events
each peak reflects the firing of large groups of neurones, within different regions
of the brain, at different times during the information processing sequence
evoked potentials are averaged to eliminate random variations in the EEG tracings
may utilise the oddball paradigm when an array of similar stimuli contains an
unexpected one
early potentials occur within the first 40 ms they are termed exogenous
potentials and are not affected by subject factors significantly (e.g. attention,
anaesthesia)
Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.
the N100 is followed by the P300 which occurs 300-500 ms after a stimulus is
presented
the P300 corresponds to the cognitive processes required for the recognition,
retrieval from memory, and evaluation of a specific stimulus
in schizophrenia, there is reduced amplitude of the P300 Response
Galvanic skin response

is a measure of autonomic arousal
shows increased arousal in chronic schizophrenia it has been suggested that
some negative symptoms are secondary strategies to reduce this hyper-arousal
is slow to habituate in some schizophrenics
may be controlled by the ipsilateral limbic system
Cerebral metabolism
Oxygen consumption
highest in the cortex and cerebellum
the brain has a respiratory quotient of 1.0, meaning that it uses carbohydrate
exclusively
Glucose utilisation
low blood glucose slows brain metabolism
glucose utilisation decreases with age
Cerebral blood flow (CBF)
investigated using xenon-133 (Ingvar, 1960s)) or nitrous oxide (Kety and Schmidt,
1940s)
xenon-133 can be injected or inhaled
in normal people, there is more blood flow to the frontal lobes
in schizophrenics, there is increased blood flow to the posterior lobes
CBF is increased by:
carotid sinus massage (increases vagal tone)
stellate ganglion blockade (causes a decrease in sympathetic stimulation)
increased CO2 concentration (hyperventilation can be used to reduce
intracranial pressure)
decreased intracranial pressure (reduced resistance to blood flow)
The GABA Shunt
the metabolism of certain glucose metabolites is closely related to that of the
glutamate group of amino acids (GABA, glutamate, aspartate)
the GABA shunt is a bypass around the Krebs cycle from -oxoglutarate to
succinate, and accounts for 10% of total glucose turnover
the importance of this pathway can be seen in Vitamin B6 deficiency:
pyridoxal phosphate is a cofactor in the enzymes glutamate decarboxylase and
glutamate transaminase, which are involved in GABA production from
glutamate
dysfunction of the decarboxylase enzyme may result in low levels of GABA

and resulting seizures
Neurotoxicology
Lead
Properties
has a strong affinity for sulphydryl groups, and it is able to alter the tertiary
structure of proteins, resulting in enzyme inhibition
the lead ion has the ability to mimic the ions of Calcium, Zinc, Magnesium, and
Copper, enabling it to disrupt many metabolic processes
Lead poisoning
presents with multiple seizures, mania, delirium, blindness, aphasia, and dementia
causes a peripheral neuropathy, predominantly motor
Alcohol
Acute intoxication
one theory proposes that alcohol acts as a non-specific membrane perturbant,
changing membrane fluidity
accounts for anaesthesia and sedation, but does not account for euphoria and
anxiety reduction at low doses
it is more likely that ethanol exerts its intoxicating effects via an action on Clfluxes associated with GABAA receptor activation it effectively potentiates
GABA inhibition
it also inhibits the excitatory actions of glutamate by interacting with the NMDA
receptor
intoxication may be due to increased production of PGE1, a prostaglandin which
has similar effects to those of ethanol
Tolerance and dependence
tolerance is partly due to an increased rate of ethanol metabolism by alcohol
dehydrogenase
theories of dependence include:
1. decremental tolerance the cell adapts in such a way to lessen the effects of
the drug
2. oppositional tolerance the response is achieved by active opposition to the
drug, and withdrawal represents the consequence of opposition in absence of
ethanol
one possibility is that TIQ derivatives (metabolites of ethanol) act as
agonists at the binding sites for enkephalins and endorphins

tolerance may be due to DGLA (a fatty acid needed for the production of
PGE1) depletion as stores become less, increased levels of ethanol are

needed to give a given level of PGE1
Neuroadaptation
reduction in the number of GABAARs or a reduction in the effects of GABA on
Cl- flux would explain dependence
chronic ingestion leads to an upregulation of the NMDA receptor an action that

would resist ethanol-induced inhibition
the prolonged presence of ethanol in the vicinity of neurones evokes, as an
adaptive response, an increased sensitivity to agonists of L-type of voltageoperated Ca2+ channels (VOCC)

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Neurophysiology

Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.

Galvanic skin response

Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.

dysfunction of the decarboxylase enzyme may result in low levels of GABA

Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.

agonists at the binding sites for enkephalins and endorphins

PGE1) depletion as stores become less, increased levels of ethanol are

Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.

chronic ingestion leads to an upregulation of the NMDA receptor an action that

Copyright Trickcyclists.co.uk 2003. Unauthorised reproduction, or commercial use prohibited.

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