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7 SEPTEMBER 2018 australiandoctor . com . au

Stemming our brain drain

INVESTIGATION Kemal Atlay
Dissecting diseased grey matter is crucial for unlocking the big mysteries in medical science . But a lack of healthy controls is hampering important research .
Professor Jillian Kril used donated samples to conduct research on alcohol-related brain damage .

PROFESSOR Jillian Kril needs brains . Healthy human brains . For more than 20 years , she has been collecting and dissecting the

brain to unlock some of the big mysteries in
medical science : Is there a cure for dementia
? Is it possible to reverse the damage of
alcohol abuse on brain tissue ?
Diseased brains have been relatively easy
to acquire — the NSW Brain Tissue Resource
Centre ( BTRC ), where she is director , houses
about 500 preserved donor cases — but it is
experiencing a chronic shortage of healthy
controls .
“ Controls are vital because almost
all research is conducted as a comparison
between healthy controls and disease
groups of interest ,” Professor Kril says .
“ Even when we are comparing between
diseases , neurologically normal controls are
included in the experimental design .”
Professor Kril explains that the brains
she has acquired over the years have been
crucial to her own field of research .
Program , which accounts for most of its dis-
brain becomes unviable and essentially use-
Raising public awareness around brain
Among more than 500 studies published
eased brain cases , the BTRC ’ s main source
less for the centre ’ s research purposes .
donor programs and signing up more con-
as a result of the BTRC ’ s extensive collection
for healthy controls has mostly dried up .
The second issue for the BTRC ’ s short-
trols can help address this issue , but she
is a paper she authored that remains one of
The NSW Department of Forensic Med-
age headache is that it can only collect
says ensuring doctors are aware of their
the most cited studies on alcohol-related
icine , which receives all sudden , acciden-
brains from the department when there has
patient ’ s donor status is paramount in pre-
brain damage . It was published in Neurosci-
tal and violent deaths , allows BTRC staff to
been a full autopsy — and not all autopsies
venting post-mortem delays in collection .
ence in 1997 . 1
visit and assess the reports of death to the
fall into this category now .
“ There ’ s a time-sensitive period where
“ It was the first work to actually show
coroner for potential donations .
Dr Claire Shepherd , director of the
they need to sign the death certificate so
that alcohol abuse did actually kill brain
If a deceased individual meets certain
BTRC ’ s sister facility the Sydney Brain Bank
that we can collect the brain tissue in as
cells ,” she says .
criteria , then the next of kin will be con-
( SBB ), says the controls shortage has had an
short a time period as possible .”
“ It demonstrated the selectivity of neu-
tacted to discuss the donation and consent-
even more profound impact on their work .
Professor Kril also wants doctors to bet-
ronal loss in people who abuse alcohol . That
ing process .
Despite owning almost 600 donor cases ,
ter assess and record patients ’ alcohol con-
is , the damage does not occur universally
“ As you can imagine , if you ’ ve just found
the number of true controls in the SBB ’ s col-
sumption , including frequency , amount ,
but targets cells in specific brain regions .”
out your relative has died and there ’ s going
lection is “ less than 2-3 %” of the total cases ,
type of alcohol consumed and dietary
This loss underlies the clinical symptoms
to be an autopsy , having someone ring up
says Dr Shepherd , who is also an Alzheim-
factors .
of a person with alcohol addiction , Professor
and say , ‘ excuse me , can I have the brain ?’
er ’ s disease researcher at UNSW .
“ Unfortunately notes often just record
Kril adds .
does sound like a terrible thing ,” Profes-
“ We should have a number of control
subjective assessments such as ‘ moderate
sor Kril says . “ But the consent rates are
cohorts that are age-appropriate and they
drinker ’ or ‘ heavy drinker ’ without the use
A lot of people found that being able to give a relative ’ s tissue for research was something they wanted to do when they were grieving .
really very high . A lot of people found that being able to give their relative ’ s tissue for research , for purely altruistic reasons , was something that they wanted to do at the time that they were grieving .”
The problem has been the chronic underfunding of the NSW Coroner ’ s Court .
In recent years the court has faced a bigger workload , partly due an increase in the
should be matched to every disease cohort we have and currently we ’ re nowhere near that ,” she tells Australian Doctor .
Dr Shepherd co-authored a 2015 study published in Nature Communications that showed that abnormalities in neuronal communication pathways contribute to synaptic loss , which is thought to be one of the earliest events in Alzheimer ’ s disease
of validated instruments ,” she says .
Not only would more detailed patient
records help fulfil the wishes of individuals
who signed up to be a donor , but it would
also create more opportunities for researchers
to continue exploring , despite its dull
goo , the most fascinating organ in the
human body .
For Professor Kril , the people who
reporting by doctors of deaths from unnat-
pathogenesis . 2
choose to take part in this great scientific
The BTRC ’ s collection holds about 150
ural causes .
“[ The study ] allows us to get a mecha-
endeavour are fascinating enough without
controls but unfortunately most are already
The state government ’ s Department
nism for how we think the nerve cells stop
having to contemplate any metaphysical
‘ matched up ’ — based on their age and gen-
of Forensic Medicine procedures are also
communicating with each other in Alzheim-
issues associated with the brain — such as
der — with diseased brains in cohort studies ,
an issue . The department must determine
er ’ s disease ,” she explains .
its link with consciousness .
leaving very few unmatched controls avail-
the cause of a person ’ s death using the
However , even this study was restricted
“ The generosity of the donors is probably
able for researchers requesting tissue sam-
least invasive procedures possible , which
by the number of controls available — only
the standout thing ,” she says .
ples outside of these parameters .
means it must review all medical records
10 were used in the study to compare with
“ I don ’ t really ponder the consciousness
“ Matching occurs dependent on selec-
of the deceased person as well as perform
disease-affected cases .
of the person , but I have a deep respect for
tion criteria . A case that is suitable for one
CT scanning on the body . It is only then , if
The SBB recruits all of its cases through
the donors and their families — the selfless-
study may be unsuitable for another because
the cause is still unclear , that an autopsy is
prospective longitudinal programs and
ness of the gift , the positivity in their altru-
the investigator has set specific inclu-
performed .
relies heavily on the BTRC to supply age-
ism and their faith in our ability as scientists
sion and exclusion criteria ,” Professor Kril
explains .
Despite having about 600 people
enrolled in its Using our Brains Donor
This process can cause delays of up to three to five days . This is a serious issue for BTRC because if it cannot collect the brain from the body within 24 hours of death , the
matched controls to researchers .
“ It would be nice to at least have at least 10-15 % of the collection being controls rather than the current 2-3 %,” Dr Shepherd says .
to deliver . It ’ s humbling .” References : 1 . Neuroscience 1997 ; 79:983-998 . 2 . Nature Communications 2015 ; online .