Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury.

OBJECTIVE

To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury.

METHODS

Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n = 6) in which the animal's core temperature was maintained at 36.0-37.5 degrees C and the hypothermia group (n = 6) in which the core temperature was reduced to 32.0-32.5 degrees C after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n = 3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system.

RESULTS

At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P < 0.001), and a significant increase in the mean intermicrotubule spacing (P < 0.05 or P < 0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P < 0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P < 0.01) and an increase in the mean intermicrotubule spacing (P < 0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P < 0.05) and reduction in the mean interneurofilament spacing (P < 0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not significant different from the mean values of sham-operated animals.

CONCLUSIONS

Posttraumatic moderate hypothermia induced immediately after axonal injury results in substantial protection of axonal cytoskeleton and ameliorates axonal damage.