Neuronal cell damage following ischaemia is postulated to be due to free radical induced lipid peroxidation, and ascorbic acid is supposedly an important non-enzymatic scavenger of such free radicals. This study was undertaken to evaluate the protective effect of ascorbic acid on the brain in a primate model after focal cerebral ischemia. Consumption of ascorbic acid in the monkey brain following ischaemia and its effect on macroscopic infarct size as demonstrated by 2, 3, 5, Triphenyl tetrazolium chloride (TTC) staining were used as parameters. The monkeys in the treated group were given 1 gram ascorbic acid parenterally every day for six days. The mean level of total ascorbic acid in right basal ganglia was 35.1 +/- 4.2 micrograms/mg of protein in the treated group as opposed to 22.9 +/- 2.1 micrograms/mg of protein in the nontreated group both before ischaemia. After right middle cerebral artery occlusion to produce focal cerebral ischaemia, the total ascorbic acid in the right basal ganglia 2 hours post ischaemia was 13.3 +/- 3.1 micrograms/mg of protein in the treated group as opposed to 9 +/- 1.6 micrograms/mg of protein in the untreated group. The average consumption of total ascorbic acid was 21.8 micrograms/mg of protein in the treated group and 13.9 micrograms/mg of protein in the nontreated group. Macroscopic infarct size as determined by TTC staining in the right cerebral hemisphere was 11.7 +/- 6.9 in treated group whereas it was 24.4 +/- 4.4 (expressed as percentage of right hemisphere) in the non-treated group. There was significant reduction in the size of the infarct in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in norepinephrine and histamine levels in the spinal cord of monkeys at 1/2, 2, and 4 hours after 200 g cm of contusion injury, 50 g of compression injury, and 2 hours of decompression following 4 hours of compression were studied in the traumatized and an adjacent nontraumatized segment. Norepinephrine levels were elevated in the traumatized segment at 1/2, 2, and 4 hours after contusion injury and in the adjacent nontraumatized segment at 1/2 hour. Compression of 1/2 and 2 hours caused elevation of norepinephrine in both the traumatized and nontraumatized segments. On decompressing the values of norepinephrine reverted to near normal levels. Histamine content increased in the traumatized segment at 2 and 4 hours after contusion injury and in the adjacent nontraumatized segment at 2 hours. Compression injury did not change histamine levels, but decompression caused an increase. The possible influence of simultaneous changes in norepinephrine and histamine levels on the vessels following injury is discussed.

Histamine levels in different regions of the brain in the primate Macaca Radiata were studied following experimental infarction induced in the basal ganglia by coagulation of the middle cerebral artery. In the basal ganglia an elevation of histamine level was seen probably due to proliferation of mast cells. In the hypothalamus, a main constituent of the ascending histaminergic neuronal pathway, a sharp rise in histamine content occurred in infarcted as well as sham-operated animals: this probably reflects non-specific stress-related alterations. In contrast, the cortical area of the ischemic hemisphere showed a higher elevation of histamine, demonstrating that infarction in one region can cause widespread specific changes in histaminergic systems remote from the infarct. The rise in histamine level at the ischemic site could evoke an increase in microcirculation which might aggravate cerebral edema, while changes in the remote regions may be responsible for some of the neurological deficits following stroke.

Physical and biochemical changes in the spinal cord of monkeys at 1/2, 2, and 4 hours following 200 g cm contusion injury and 50 g of compression injury and 2 hours of decompression following 4 hours of compression were studied. The pathophysiologic changes were milder in compression compared to contusion injury. Following contusion injury, at 1/2 and 2 hours there was significant increase in % water content, lipid peroxidation, and alpha-L-fucosidase. alpha-D-Mannosidase was significantly increased at all time periods, and beta-D-hexosaminidase was increased at 1/2 and 4 hours. At 4 hours following injury, serotonin (5 HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) showed a significant increase. From 10 minutes to 2 hours there was increased platelet aggregation. In compression injury, a significant increase in water content and 5 HT was observed only at 1/2 hour. Lipid peroxidation had increased at all time periods, whereas B-D-hexosaminidase, beta-D-galactosidase, and 5-HIAA were increased at 2 hours. alpha-D-Mannosidase had increased at 1/2 and 2 hours, and alpha-L-fucosidase had increased at 4 hours. After 2 hours decompression following 4 hours compression, water content, beta-D-galactosidase, and alpha-D-Mannosidase were significantly increased. An attempt was made to correlate the findings and to understand the sequential pathophysiologic changes in the first 4 hours following spinal cord trauma, providing a baseline for evaluation of the efficacy of any therapeutic maneuvers.

Experimental focal cerebral ischemia was produced in monkeys (Macaca radiata) by occlusion of the right middle cerebral artery (MCA). The release of the lysosomal glycosidases, beta-D-hexosaminidase, alpha-L-fucosidase and alpha-D-mannosidase into the soluble fraction in the right basal ganglia of the experimental animals was measured at different periods from 30 min to 12 hr after occlusion and compared with the corresponding sham operated control animals. There was a significant increase in the released lysosomal enzymes in the MCA occluded animals at all periods and particularly at 4 hr after occlusion. The CSF from the experimental animals also showed elevated levels of hexosaminidase and fucosidase. The free fatty acids (FFA) measured in the basal ganglia at 30 min and 2 hr after occlusion showed a 100 fold increase in the experimental animals. The predominant fatty acid released was linoleic acid (18:2) followed by arachidonic acid (20:4). Lipid peroxidation in the basal ganglia measured by the thiobarbituric acid (TBA) reaction in the presence or absence of ascorbic acid also showed a significant increase in the experimental animals at all periods with a maximum at 30 min to 2 hr after occlusion. In order to assess whether lipid peroxidation causes damage to the lysosomes and release of the enzymes, a lysosome enriched P2 fraction from the normal monkey basal ganglia was prepared and the effect of peroxidation studied. Maximum peroxidation in the P2 fraction was observed in the presence of arachidonic acid, ascorbic acid and Fe2+.(ABSTRACT TRUNCATED AT 250 WORDS)