Lucy suffers from a disorder affecting a part of her brain that controls movement

before her operation she was confined to a chair and had difficulty eating and

breathing

without surgery that could only have been developed through animal research

Lucy could have died

she now has a new lease of life

the brain is the most complex organ in our body

it is not just a sum of all its component pieces

it is much more than that

indeed, it is one of the most complex organ we have ever tried to understand

and how it does what it does, is still largely a mystery

this means that research techniques focusing on a small part of the brain or

single pathway cannot tell the whole story

to get to grips with its complexity

we need to look at living brain

the entire brain

and how it interacts with other organs

the brain controls every aspect of our lives

from regulating our heartbeat and emotions to movement and speech

however, unlike a heart or any other organ it can't be replaced

when things go wrong

and at the moment, there are no cures for diseases of the brain

some disorders affecting the central nervous system are genetically driven

as a child you have no influence on your genetic makeup

which could predispose you to disorders like Schizophrenia

Parkinson's disease or Alzheimers

in addition anyone of us could have an accident and be left paralyzed

well the common causes of spinal cord injury are things that

could happen in everyday life, so they are things like automobile accidents

and also for example, a lot of sporting injuries can cause spinal cord injury

and if we take the famous case of Christopher Reeve, he actually fell off his horse

and then develped paraplegia

but at the moment there are a number of experimental techniques which are being

developed which may potentially be the treatments of tomorrow for treating

spinal cord injury

so at the moment the majority of research looking at spinal cord injury, involves

looking at rodents, in particular rats

and what we do is, we look at the ability of a chemical, an enzyme called

Chondroitinase, which has being shown to allow regeneration of nerve fibres

in the spinal cord, to quite considerable distances.

When the spinal cord is injured

scar tissue forms, it is partly comprised of the cell type called ghlea

this acts as a physical barrier to nerve regrowth.

Chondroitinase may help

it's thought to break down the constituents of the gleaus scar and therefore reduce

the inhibitory environment that the

injured nerve fibre faces after injury.

You couldn't do this on humans for a number of reasons, the first major reason

is because Chondroitinase is actually toxic to humans, so the doses that you

would require to get functional recovery are just too great

but using our animal models we can look at this drug and we can look at the

active sites and how it could actually exert its action

and divise an analogue pharmaceutically which could then be used in humans

the second reason is obviously that you can't look at histology

you can't look at post mortem of patients because you have to wait a very long

time for them to actually expire and then to remove the spinal cord, whereas

with rats it allows us to do this over a relatively short period of time.

The same problems hold true when using post-mortem brains to study mental illness

the drawback of studying things in post mortem brain is of course people have typically

died of old age, often in an institution

and they have been exposed to 30, 40 years of drug treatment

and a very isolated kind of existence, so it's diffcult to find controlled people

where all of that is matched

you can't match the effects of the drug and you can't match the effect of lifestyle

in that situation

The difficulties in using human tissues are partly overcome by using animals, whose environment we

can control

in the case of an introduced spinal cord injury

the animal still has normal function in one side of the body

this means that the recovery following treatment in the injured side

can be compared with the normal in a series of behavioral tests.

There is something called the sticky tape test

and essentially what this involves is a piece of sticky tape attached to the

rodent's paw

and it has to sense that this sticky tape is there and because it's not very

comfortable for the animal it will then rip off the sticky tape

and therefore you can assess 2 things you can assess the sensory

benefits and

regained after application of Chondroitinase because it can feel the sticky tape

to pull it off

and also the motor responses because in order to pull it off

it needs some sort of motor ability

the staircase test also measures

mice are placed inside a small chamber where they have to walk along the stationary

platform to retrieve the series of tiny sugar treats

they can only use the right port to reach the right stair case

and the left port to reach the left

animals with the spinal lesion on one side

finds this difficult to do on the side that is injured.

Then there is a water maze task

commonly used to assess memory impairment following stroke

animals have to find a submerged platform hidden in a murky pool of water

they use visual cues from around the room

the position of the door or window for example

to remember where the platform is

once they find it they are taken out of the pool, towel dried and back to cage

those that struggle with the task are fished out after a couple of minutes.

In spinal cord injury, the challenge is to regenerate the damaged nerve cells

for stroke patients it is the opposite

here the difficulty lies in preventing cell death.

Strokes are very big problem in the world, it is the second biggest killer globally

and in Britain that translates to 1 in person in every 5

minutes having a stroke

it is a massive problem and one of the worst things about stroke is that even

if you survive

a lot of people who do survive are left with other kinds of disability such as

paralysis, impairment, their vision, their memory can be effected so it's a very

debilitating disease

a stroke is caused when the blood supply to the brain is stopped quickly

and dramatically. What happens when you get the stroke is that region of the brain that

stops receiving this blood supply, stops getting oxygen, stops getting glucose and

the cells in the immediate area start to die

and there is nothing we can do about that

but what also happens is that subsequently there is a period of hours

which can extend to days of what we call the delayed cell death

Barry studies basic biology of stroke

many different molecules are involved

understanding what they do and how they interact may help researchers devise new

anti stroke therapies

We couldn't do what we are doing without using animals.

The brain is such a complex organ, the most complex in the human body

you can't simply take it apart and look at individual cells, every single one of the

cells in the brain, in a living brain has thousands of other connections with lots

of other cells and you need to keep that integrity you need to keep

those cells in contact.

In the UK, there is some work going on with a naturally produced chemical in our body called

Interleukin-1

what they found in tissue culture was that appeared interleukin-1 was

actually protective

to the cells and it reduced damage to those cells. However, when they went on to

actually look at this chemical in animal models, they found it was actually

quite damaging and had this chemical gone on to be used in humans, it could

have actually been fatal.

So now thanks to this work in Manchester using animals they have been able to

develop certain types of drugs to block the action of Interleukin-1 and those are

now in clinical trials.

This is the new treatment in the evaluation stages

another treatment for stroke used worldwide is constraint induced therapy.

It basically involves restricting the movement of the side of the body that

is unaffected by stroke

forcing the damaged side to perform the tasks

it sounds obvious

but the simple treatment is a direct result of studies in monkeys that showed the

brain could undergo massive physical reorganization in response to damage

that means over time, the nerve cells

actually grow and make new connections.

Stroke is a serious problem, about 10% of those that suffer a stroke are children

but in terms of the effect it has on people's lives

mental health problems exert a wider influence.

At some point in our lives, 1 in 4 of us will develop a mental health

problem

so how do we study mental illness in animals? It's very difficult to model a mental illness in animals

How do you model a hallucinations or a delusion?

How do you model depression?

and feeling unhappy and suicidal and so forth

but it can be done, the 2 main approaches are

first of all

to observe the effects of drugs that we know cause these disorders

so there are certain drugs that cause hallucinations and delusions in humans like LSD for example.

Well, PCP has been taken as recreational drug and had been taken quite widely in

like the 70's

so it was observed that

individuals exhibited physcotic response, very similar to that of Schizophrenics

and that Is why we knew that we could use these drugs in rats to model the disorder

the rat model of Schizophrenia that I was using was focused primarily on the attentional

deficits that are

exhibited in psychotic patients

they find it very

well in a lot of cases, they find it very difficult to concentrate on something

so I could be talking to someone and they can be distracted by

the noise of something coming through the window or the light or

something else that is

being said to them

so that's the part that I primarily focused on

but there are lots of other models of schizophrenia focusing on the

other symptoms. Using drugs to induced symptoms is one approach

Bill describes another which is used in studies of depression

when someone is depressed things like having dinner with your family or a

drink with friends holds no pleasure

so we can model in animals

a loss of pleasure

one way of doing that is to see whether animals prefer sucrose to

water

normal rats prefer that, if they have been stressed in some gentle way

then they lose that preference

and that is a model for what we call Anhedonia, the loss of reward

and then we can try and reverse that with drugs that may be effective in

depression

and all the ones that are affective in depression

have that ability. The kind of thing that is done these days is to

use mild stress upon it, mild stress model of depression for example where

it's where you sort of mess about with the daily routine of a mouse

so that the litter that the animal lives in is not cleaned out on time

the water doesn't arrive on time, the light bulb cycle is messed about with

and they are isolated for a bit

there are many ways of trying to induce a state of Anhedonia using

rather mild amd ethical kinds of stress

I think for all mental illnesses actually

the outlook has changed dramatically in the last 25 years

mainly due to improvement in

how anti-depressant drugs work, the development of new anti-depressant drugs, and the developmnet of new

anti-psychotic drugs. To see somebody just get better from a simple depressive

illness, to see somebody who is floridly psychotic

recover and acheive a normal life again

and to see somebody who is a manic-depressive

whose mood is either up or down and has been like that for years and just to get the

medication right

is one of the most satisfying aspects of my job

the improvements we have seen are just remarkable

As we age, we are more likely to succumb

to Parkinson's disease, Alzheimer's disease or suffer a stroke

There are treatments but there are very few cures

at the Charing Cross hospital, Tipu is a surgeon who treats patients with

Parkinson's disease

the therapy that he carries out 3 days a week was developed in animals

Recently

really in the last 10 years

the use of primate models of Parkinson's disease has allowed us

to find the central targets in the brain that drive the symptoms