In our extensive study of the brain in its relation to the production
of energy and the consequent exhaustion caused by fear and rage;
by the injection of foreign proteins, of bacterial toxins,
and of strychnin; by anaphylaxis; by the injection of thyroid extract,
of adrenalin, and of morphin, we found that, with the exception
of morphin, each of these agents produced identical changes in
the brain-cells. As we believed that the adrenals were intimately
associated with the brain in its activities, we concluded that
the adrenals also must have been affected by each of these agents.
To prove this relation, we administered the above-mentioned
stimuli to animals and studied their effects upon the adrenals
by functional, histologic, and surgical methods, the functional
tests being made by Cannon's method.
Functional Study of the Adrenals.--Our method of applying
the Cannon test for adrenalin was as follows: (_a_) The blood
of the animals was tested before the application of the stimulus.
If this test was negative, then (_b_) the stimulus was applied
and the blood again tested. If this second test was negative,
a small amount of adrenalin was added. If a positive reaction
was then given, the negative result was accepted as conclusive.
(_c_) If the control test was negative, then the stimulus was given.
If the blood after stimulation gave a positive result for adrenalin,
a second test of the same animal's blood was made twenty-five minutes
or more later. If the second test was negative, then the positive
result of the first test was accepted as conclusive.
We have recorded 66 clear-cut experiments on dogs, which show that
after fear and rage, after anaphylaxis, after injections of indol
and skatol, of leucin and creatin, of the toxins of diphtheria and
colon bacilli, of streptococci and staphylococci, of foreign proteins,
and of strychnin, the Cannon test for adrenalin was positive.
The test was negative after trauma under anesthesia, and after
intravenous injections of thyroid extract, of thyroglobin,
and of the juices of various organs injected into the same animal from
which the organs were taken. Placental extract gave a positive test.
The test was sometimes positive after electric stimulation
of the splanchnic nerves. On the other hand, if the nerve supply
to the adrenals had been previously divided, or if the adrenals
had been previously excised, then the Cannon test was negative
after the administration of each of the foregoing adequate stimuli.
Blood taken directly from the adrenal vein gave a positive result,
but under deep morphinization the blood from the adrenal vein
was negative, and under deep morphinization the foregoing adequate
stimuli were negative.
In brief, the agencies that in our brain-cell studies were found to
cause hyperchromatism followed by chromatolysis gave positive results
in the Cannon test for adrenalin (Fig. 62). The one agent which was
found to protect the brain against changes in the Nissl substance--
morphin--gave a negative result in the Cannon test for adrenalin.
After excision of the adrenals, or after division of their nerve supply,
all Cannon tests for adrenalin were negative.
Histologic Study of the Adrenals.--Histologic studies of the adrenals
after the application of the adequate stimuli which gave positive
results to the Cannon test for adrenalin are now in progress,
and thus far the histologic studies corroborate the functional tests.
In hibernating woodchucks, the cells of the adrenal cortex were found
to be vacuolated and shrunken. In one hundred hours of insomnia,
in surgical shock, in strong fear, in exhaustion from fighting,
after peptone injections, in acute infections, the adrenals undergo
histologic changes characteristic of exhaustion (Figs. 66 to 67).
We have shown that brain and adrenal activity go hand in hand,
that is, that the adrenal secretion activates the brain, and that
the brain activates the adrenals. The fundamental question which now
arises is this: Are the brain and the adrenals interdependent?
A positive answer may be given to this question, for the evidence
of the dependence of the brain upon the adrenals is as clear as is
the evidence of the dependence of the adrenals upon the brain.
(1) After excision of the adrenals, the brain-cells undergo
continuous histologic and functional deterioration until death.
During this time the brain progressively loses its power
to respond to stimuli and there is also a progressive loss
of muscular power and a diminution of body temperature.
(2) {illust. caption = FIG. 66.In our crossed circulation experiments
we found that adrenalin alone could cause increased brain activity,
while histologically we know that adrenalin alone causes an increase
of the Nissl substance. An animal, both of whose adrenals
had been excised, showed no hyperchromatism in the brain-cells
after the injection of strychnin, toxins, foreign proteins, etc.
(3) When the adrenal nerve supply is divided (Cannon-Elliott), then
there is no increased adrenal activity in response to adequate stimuli.
From these studies we are forced to conclude not only that the brain
and adrenals are interdependent, but that the brain is actually
more dependent upon the adrenals than the adrenals upon the brain,
since the brain deteriorates progressively to death without the adrenals,
while the adrenal whose connection with the brain has been broken
by the division of its nerve supply will still produce sufficient
adrenalin to support life.
From the strong affinity of the brain-cells for adrenalin which was
manifested in our experiments we may strongly suspect that the Nissl
substance is a volatile, extremely unstable combination of certain
elements of the brain-cells and adrenalin, because the adrenals alone
do not take the Nissl stain and the brain deprived of adrenalin
also does not take Nissl stain. The consumption of the Nissl
substance in the brain-cells is lessened or prevented by morphin,
as is the output of adrenalin; and the consumption of the Nissl
substance is also lessened or prevented by nitrous oxid.
But morphin does not prevent the action of adrenalin injected
into the circulation, hence the control of morphin over energy
expenditure is exerted directly on the brain-cells. Apparently morphin
and nitrous oxid both act through this interference with oxidation
in the brain. We, therefore, conclude that within a certain range
of acidity of the blood adrenalin can unite with the brain-cells
only through the mediation of oxygen, and that the combination
of adrenalin, oxygen, and certain brain-cell constituents
causes the electric discharge that produces heat and motion.
In this interrelation of the brain and the adrenals we have what is,
perhaps, the master key to the automatic action of the body.
Through the special senses environmental stimuli reach the brain
and cause it to liberate energy, which in turn activates certain
other organs and tissues, among which are the adrenals. The increased
output of adrenalin activates the brain to still greater activity,
as a result of which again the entire sympathetic nervous system
is further activated, as is manifested by increased heart action,
more rapid respiration, raised blood-pressure, increased output
of glycogen, increased power of the muscles to metabolize glucose, etc.
If this conclusion be well founded, we should find corroborative evidence
in histologic changes in that great storehouse of potential energy,
the liver, as a result of the application of each of the adequate
stimuli which produced brain-cell and adrenal changes.