Pathological and biochemical studies of unilateral cold induced brain edema in the rat.

Abstract

This study was carried out to clarify the biochemical changes in the cold injured brain and their relationship to pathological changes. The cold lesion was produced by application of a cryoprobe containing liquid nitrogen to the exposed left temporal surface for 1 minute in rats anesthetized with a halothane and oxygen gas mixture. The brain edema developed by this procedure was localized in one hemisphere. The animals were guillotined at scheduled times after the cold injury. The brains were rapidly removed and divided exactly between the two hemispheres. Changes in specific gravity of the brain tissue were measured by the dry-weight method until 4 weeks after the injury. Hematoxylin-eosin and Kliiver-Barrera stains were applied to pathological specimens. Free amino acid and uric acid levels were measured chronologically by using Iriyama's method. Catecholamine levels were analyzed by using high-performance liquid chromatography with electrochemical detection. Water content in the injured hemisphere reached a peak level at 12 hours after the injury, then decreased gradually, and entered the normal range at 1 week after the injury. This results was similar to the previous report. Multiple small hemorrhagic lesions were disclosed 2 hours after the injury. This suggests that a mechanism similar to hemorrhagic infarction might play a role in the development of cold injury. Essential amino acids were increased in the injured hemisphere, while those in the contralateral side remained within normal ranges. This result suggests that, in the injured hemisphere, there was not only nonutilization of the essential amino acids but also disturbance of the blood brain barrier, and that the aerobic glycolytic pathway was maintained normally in the contralateral hemisphere. Norepinephrine and dopamine were lowered, while tyrosine was increased in the early stage of cold injury. This suggests impairment of the catecholamine synthesis followed by nonutilization of catecholamine precursors. Uric acid level was increased immediately after the injury, especially on the injured side, and lowered to near baseline level at 4 weeks after the insult. Although biosynthesis of uric acid in the brain is not fully understood, it seems to be a fine parameter of brain damage.