An overview of developments in research on recovery from brain injury.
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Biomedical subjects
Publications and source records attributed to D G Stein.
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Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.
Adult male rats were given 6-hydroxydopamine lesions of the nucleus accumbens, followed immediately by injections of saline or nerve growth factor (NGF; 125 B.U.) near the substantia nigra. Such lesions were previously reported to attenuate the locomotor response to D-amphetamine. NGF-treated rats showed an enhanced response to D-amphetamine (1.5 mg/kg) when tested 15 days postoperatively. Levels of dopamine and norepinephrine in the striatum and nucleus accumbens were equivalently depressed in the two lesion groups, indicating that the apparent recovery of the NGF-treated rats was probably not due to catecholaminergic neuronal regrowth. Intracerebral NGF administeration enhanced the response to D-amphetamine 15 days later in rats without lesions, and also appeared to result in increased turnover of brain norepinephrine and serotonin at 3, but not 15, days postadministration. NGF might increase dopamine turnover at 15 days, but the evidence obtained did not convincingly confirm or negate this possibility. The results in brain-damaged and intact rats, and also modify the apparent turnover of brain monoamines.
In rats, spontaneously occurring tumors and infarcts induce damage which destroys or distorts regions of the brainstem and cerebral hemispheres. Despite such destruction, there may be no gross evidence of behavioral or metabolic pathology.
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Bilateral transections of the later olfactory (LOT) in male hamsters at the rostral border of the olfactory tubercle or anterior to the tubercle produced severe deficits in mounting, scent marking, food hoarding and nesting behaviors. There were no impairments of these behaviors following unilateral transections. Cutting of the LOT in two stages, and provision of additional experience in sexual and territorial behaviors during the interval between the first and second transection, did not alleviate the behavioral deficits. Impairments in mounting and scent marking were dissociated in some subjects, indicating individual differences in the hamsters' dependence on chemosensory cues for the regulation of these two types of social behavior. It is suggested that the apparent sparing of behavioral function which has been associated with gradual destruction of nervous tissue is due to the development of alternate mechanisms of response to environmental cues, and may be more difficult when brain damage is in structures which initially process these cues. Although sexual and territorial behaviors in the hamster are dependent on gonadal hormones, the observed impairments of these behaviors could not be explained as indirect consequences of lesion effects on the hypophysiogonadal axis. Circulating testosterone (T) levels in experimental subjects were not different from levels in control (sham-operated) subjects. An inverse correlation was observed between the control subjects' circulating T levels and their incidence of scent marking. A similar correlation was observed between postoperative T levels and preoperative marking rates in experimental subjects, despite the fact that most subjects failed to scent mark after bilateral LOT transections. The latter observation strengthens the inference that the bilateral deficits were independent of changes in basal hormone levels.
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Blood was collected from 14 baboons 3 - 5 min, 30 min and 60 min after the intramuscular injection of phencyclidine at a dosage rate of 1,5 mg/kg body mass. The determination of blood chemistry and haematology was then undertaken. An abrupt decrease in total plasma protein occurred after the injection of phencyclidine but thereafter it remained at approximately the same level. The sodium, potassium, chloride and cholesterol remained practically unaltered throughout. A significant decrease occurred in the blood urea level. The blood sugar value showed a highly significant decrease over the first 30 min period and less over the second 30 min period. Plasma enzyme activity and corticosteroid levels did not show marked alterations. Marked and significantly lowered values occurred in white blood cell count, erythrocyte count, haemoglobin concentration and haematocrit level but these values returned to within normal limits at 60 min.
Rats with bilateral lesions of the caudate nucleus received intracaudate injections of either nerve growth factor protein (NGF) on inert buffer immediately following surgery. NGF-treated animals demonstrated a faster recovery of normal appetitive behavior and perseverated less than their buffer-treated counterparts on a spatial reversal task, but both groups were impaired relative to sham controls on acquisition of an active avoidance response. Glia to neuron ratios were significantly increased in both lesion groups when compared with sham controls. However, this increase was less in the NGF-treated animals than in the buffer-treated animals. NGF treatment had no effect on steady-state caudate dopamine levels, measured six months after surgery.