Hypoxia-provoked Morphologic Changes in the Central Nervous System

Study of the morphologic changes provoked by hypoxia in the central nervous system deserves great attention. It is quite evident that determination of the character and degree of death, and of the reversibility of the changes occurring during it, will let us get closer to resolving such an important problem as prognostication of the outcome of resuscitation. 

Morphologic studies of the brain during the postreanimation period established the presence of diffuse chan­ges of a hypoxic nature in the nerve cells, glia, fibres, and vessels. One to three hours after cardiac activity had been restored, distinct changes in the central nervous system were observed, which in­creased in the following hours and days, and stabilized after five or six days. A process of reverse development then began.

By studying the brains of animals over a lengthy period it was established that a considerable part of the damage observed during the first few days after resuscita­tion was reversible. Acute hypoxic lesions disappeared after five to seven days. Vacuolization of the protoplasm and alterations in argyrophile fibres persisted for more than a month. It should be noted, however, that despite the process of reverse development, some nerve cells perished all the same. The cortex, hippocampus, and cerebellum were most vulnerable; the brain stem was damaged much less, and changes in the amygdaloid nucleus were not prac­tically observed.

The severity and degree of the lesions in the central nervous system depend on the causes bringing on the terminal state, and also on the character and duration of the periods of dying and clinical death. It is important to emphasize that the measures applied during the restorative period also affect the extent of the pathological alterations.

Thus when plasmaphaeresis or total blood substitution is employed in the early postreanimation period the severity and extent of the brain damage after 12 minutes of circulatory arrest approximates to what has been observed in dogs that have experienced circulatory arrest for only 7-8 minutes, but have not had such treatment. In other words, this detoxication therapy allows the resistance of the central nervous system to severe hypoxia to be almost doubled. There are grounds for believ­ing that the pathomorphologic alterations are due not only to oxygen starvation per se, but also to its effects, in other words to the action of the toxic metabolites that accumulate in the orga­nism in the restoration period.

All other conditions being equal the functional state of the central nervous system affects both the outcome of resuscitation and the degree of the morphologic alterations. Motor excitation during dying causes more severe lesions to the brain; sleep therapy diminishes the degree of damage.

There is no complete parallelism, it should be noted, between the renewal of functions and restoration of the morphologic sub­stratum. Morphologic restoration takes place considerably later and may be less complete than that of functions, which indicates that the central nervous system has great compensatory possibi­lities.

In recent years we have attempted in our Laboratory to develop methods for quantitative determination of the degree of the func­tional and morphologic changes developing in the brain tissue as a result of oxygen starvation. In this con­nection we first considered the earlier finding of a stable and significant decrease in the high frequency component of the EEG in some resuscitated dogs with outwardly normal behaviour, and the fact that this decrease, and sometimes also an increase coin­cided with the perishing of cells in the cerebral cortex.

The morphologic alterations were measured by the degree of quantitative decrease of the Purkinje cells of the cerebellum in 100 fields of vision and compared with the degree of morphologic al­terations in other sections of the brain.

Studies made three or four weeks after the experiment indicated a correlation between the alterations in the EEG frequency oscil­lations, the decrease in the number of the Purkinje cells, and the severity of the organic lesions in the cerebral cortex of reanimated animals.

These findings led to the conclusion that the normal amplitude of the high frequency component of the EEG can remain on a background of distinct functional and moderate organic alterations in the structure of brain tissue and is thus not an indication of normalization of the structure. But the fact of such an EEG can be taken as a reliable sign of the re­latively low degree of such alterations.

A more than 30 per cent increase in the average amplitude of the high frequency component of the EEG of dogs over the value observed prior to ischaemia is a reliable indication of the presence of diffused not sharply expressed functional and organic changes in cortical cells, and of a moderate reduction in the number of the Purkinje cells in the cerebellum, which is compatible with complete apparent normalization of the animals behaviour.

A drop in the average amplitude of the high frequency component by 25 to 50 per cent of the original level points to the presence of wide spread small foci of extinction of neurons through­out the cortex, and of considerable functional impairment of the remaining neurons, marked lesions of the hippocampus, and as much as a 50 per cent reduction in the number of the Purkinje cells in the cerebellum; these alterations are also compatible, however, with apparent complete normalization of the animals behaviour. Lastly, a decrease in the average amplitude of the high frequency component by more than 50 per cent of the original level is a reliable sign of wide spread gross degenerative processes in the cerebral cortex, the hippocampus and the cerebellum, and goes hand in hand with marked impairment of the animals neuro­logical state.

The correlation between the volume of the extinction of the Pur­kinje cells and the level and extent of the changes in other sectors of the brain and the neurological state also proved to be very clear-cut and reliable. A less than 25 per cent reduction in the number of the Purkinje cells indicated the presence of wide spread functional changes and moderate organic alterations in the tissue of the cerebral hemispheres, that were, however, completely compensated functionally.

A 25 to 50 per cent reduction in the number of the Purkinje cells was associated with con­siderable, wide spread alterations in the brain tissue, which, however, also were not reflected in the animal’s outward behaviour and neurological state. The extinction of over 50 per cent of the Purkinje cells was observed with gross, wide spread organic lesions of the cortex of the cerebral hemispheres and the hippo­campus and was incompatible with complete restoration of neuro­logical functions.