Secondary hypoxemia exacerbates the reduction of visual discrimination accuracy and neuronal cell density in the dorsal lateral geniculate nucleus resulting from fluid percussion injury.

The purpose of this study was to determine the impact of secondary hypoxemia on visual discrimination accuracy after parasagittal fluid percussion injury (FPI). Rats lived singly in test cages, where they were trained to repeatedly execute a flicker-frequency visual discrimination for food. After learning was complete, all rats were surgically prepared and then retested over the following 4-5 days to ensure recovery to presurgery levels of performance. Rats were then assigned to one of three groups [FPI + Hypoxia (IH), FPI + Normoxia (IN), or Sham Injury + Hypoxia (SH)] and were anesthetized with halothane delivered by compressed air. Immediately after injury or sham injury, rats in groups IH and SH were switched to a 13% O2 source to continue halothane anesthesia for 30 min before being returned to their test cages. Anesthesia for rats in group IN was maintained using compressed air for 30 min after injury. FPI significantly reduced visual discrimination accuracy and food intake, and increased incorrect choices. Thirty minutes of immediate posttraumatic hypoxemia significantly (1) exacerbated the FPI-induced reductions of visual discrimination accuracy and food intake, (2) further increased numbers of incorrect choices, and (3) delayed the progressive recovery of visual discrimination accuracy. Thionine stains of midbrain coronal sections revealed that, in addition to the loss of neurons seen in several thalamic nuclei following FPI, cell loss in the ipsilateral dorsal lateral geniculate nucleus (dLG) was significantly greater after FPI and hypoxemia than after FPI alone. In contrast, neuropathological changes were not evident following hypoxemia alone. These results show that, although hypoxemia alone was without effect, posttraumatic hypoxemia exacerbates FPI-induced reductions in visual discrimination accuracy and secondary hypoxemia interferes with control of the rat's choices by flicker frequency, perhaps in part as a result of neuronal loss and fiber degeneration in the dLG. These results additionally confirm the utility of this visual discrimination procedure as a sensitive, noninvasive means of assessing behavioral function after experimental traumatic brain injury.

Hypoxia potentiates traumatic brain injury-induced expression of c-fos in rats.

Halothane-anesthetized male rats were subjected to either moderately severe parasagittal fluid percussion-induced traumatic brain injury (TBI) or sham injury, and for 30 min immediately after injury hypoxia was induced in half the rats from each group by substituting a 13% O2 source to deliver halothane for continued anesthesia. At 60 min post-TBI, Northern blot analysis showed a significant increase in c-fos mRNA levels, by 60-100% above sham control levels in the frontal cortex, cerebellum and hippocampus. Although hypoxia in sham-injured rats did not by itself alter c-fos mRNA levels, it did significantly potentiate the TBI-induced changes in c-fos mRNA in all three brain regions. These findings show that hypoxia is an important factor influencing genomic responses to TBI.

Arteether: risks of two-week administration in Macaca mulatta.

Male rhesus monkeys (Macaca mulatta) were administered daily doses of the antimalarial drug arteether. The 14-day treated group received either 24 mg/kg/day, 16 mg/kg/day, or 8 mg/kg/day. The seven-day treatment group received either 24 mg/kg/day or 8 mg/kg/day. All control cases in each group received the sesame oil vehicle alone. Neurologic signs were absent for animals in the seven and 14-day treatment groups except for one monkey which showed diffuse piloerection on day 14, and another monkey receiving 24 mg/kg/day for seven days showed mild lethargy after the fourth day. Mild, sporadic anorexia was noted in all animals by day 14, and a single animal showed diffuse piloerection on day 14. Surgical anesthesia preceded killing by exsanguination and was accompanied by perfusion fixation of the central nervous system. Brain sections were cut and then stained for study by light microscopy. Evidence of neuronal pathology, both descriptive and numerical, was collected. The neuroanatomic and neuropathologic findings demonstrated that arteether produced extensive brainstem injury when administered for 14 days. The magnitude of brainstem neurotoxicity was dose-dependent, where injury was greatest at the 24 mg/kg/day dose level, less at the 16 mg/kg/day dose level, and least at the 8 mg/kg/day dose level. Arteether induced multiple systems injury to brainstem nuclei of 1) the reticular formation (cranial and caudal pontine nuclei, and medullary gigantocellular and paragigantocellular nuclei); 2) the vestibular system (medial, descending, superior, and lateral nuclei); and 3) the auditory system (superior olivary nuclear complex and trapezoid nuclear complex). The vestibular nuclei and the reticular formation were most severely injured, with the auditory system affected less. The cranial nerve nuclei (somatic and splanchnic) appeared to escape damage, with the exception of the abducens nerve nucleus. The same brainstem nuclear groups of seven-day treated monkeys appeared normal. The statistical data are concordant with the descriptive data in demonstrating neurotoxic effects. In summary, no neurologic deficits were detected in any of the vehicle control monkeys (14-day and seven-day cases). Monkeys in the 14-day treatment group were free of clinical neurologic signs throughout the first week. At day 14, fine horizontal nystagmus was seen in one monkey, and another monkey exhibited diffuse piloerection. Monkeys in the seven-day treatment group were free of clinical neurologic signs except for one case. This monkey was treated with 24/mg/kg/day of arteether and exhibited lethargy after the fourth day. These indications of dysfunction arose too late to be practical indicators of neurotoxicity.

Automation of film library functions.

The use of computer routines in the film library has resulted in tremendous improvements in the prompt interpretation of radiologic studies with comparison studies and in the furnishing of radiologic studies on demand to referring physicians. The four most important aspects of this automation are the simultaneous immediate availability of patient information upon inquiry at a terminal; maximum advance notification of the need for a new folder or a master folder on a returning patient; master folder, subfolder, and examination folder tracking; and the management of extradepartmental loans.

The registration and scheduling processes.

The entry of patient information via a computer registration system eliminates the manual and repetitive handling of patient information in many different operations. Present scheduling systems range to the very sophisticated that not only smooth peaks and valleys but also eliminate examination conflicts and unnecessary, similar, and duplicate examinations to increase departmental productivity using the existing radiographic rooms and technologic staff.

Reporting and communications.

The future of radiology reporting will be molded by the ever changing health care environment and developments in computer methods. Less reliance on transcription is certain. The challenges of producing faster and more useful reports should be rewarding in a positive sense. The next few years should include many computer approaches to help the radiologist to generate reports directly and to communicate them effectively.

The era of health care reform and the information superhighway. Implications for radiology.

Radiology is undergoing dramatic change, along with the rest of the health care system, in its mode of organization, financing, and delivery. Information technology is becoming central to health care delivery and will enable a higher degree of integration of imaging practice with the rest of the health care system. Radiology will need to address the requirements for achieving this integration to continue to be successful in the future.

Visual system degeneration induced by blast overpressure.

The effect of blast overpressure on visual system pathology was studied in 14 male Sprague-Dawley rats weighing 360-432 g. Blast overpressure was simulated using a compressed-air driven shock tube, with the aim of studying a range of overpressures causing sublethal injury. Neither control (unexposed) rats nor rats exposed to 83 kiloPascals (kPa) overpressure showed evidence of visual system pathology. Neurological injury to brain visual pathways was observed in male rats surviving blast overpressure exposures of 104-110 kPa and 129-173 kPa. Optic nerve fiber degeneration was ipsilateral to the blast pressure wave. The optic chiasm contained small numbers of degenerated fibers. Optic tract fiber degeneration was present bilaterally, but was predominantly ipsilateral. Optic tract fiber degeneration was followed to nuclear groups at the level of the midbrain, midbrain-diencephalic junction, and the thalamus where degenerated fibers arborized among the neurons of: (i) the superior colliculus, (ii) pretectal region, and (iii) the lateral geniculate body. The superior colliculus contained fiber degeneration localized principally to two superficial layers (i) the stratum opticum (layer III) and (ii) stratum cinereum (layer II). The pretectal area contained degenerated fibers which were widespread in (i) the nucleus of the optic tract, (ii) olivary pretectal nucleus, (iii) anterior pretectal nucleus, and (iv) the posterior pretectal nucleus. Degenerated fibers in the lateral geniculate body were not universally distributed. They appeared to arborize among neurons of the dorsal and ventral nuclei: the ventral lateral geniculate nucleus (parvocellular and magnocellular parts); and the dorsal lateral geniculate nucleus. The axonopathy observed in the central visual pathways and nuclei of the rat brain are consistent with the presence of blast overpressure induced injury to the retina. The orbital cavities of the human skull contain frontally-directed eyeballs for binocular vision. Humans looking directly into an oncoming blast wave place both eyes at risk. With bilateral visual system injury, neurological deficits may include loss or impairments of ocular movements, and of the pupillary and accommodation reflexes, retinal hemorrhages, scotomas, and general blindness. These findings suggest that the retina should be investigated for the presence of traumatic or ischemic cellular injury, hemorrhages, scotomas, and retinal detachment.

Exposure to sublethal blast overpressure reduces the food intake and exercise performance of rats.

Exposure to blast overpressure can typically inflict generalized damage on major organ systems, especially gas-containing organs such as the lungs and the gastrointestinal tract. The purpose of the present study was to use rat's food intake and exercise wheel running as behavioral correlates of the perhaps more subtle damage to these organ systems induced by sublethal blast overpressure. Toward this end, all rats were exposed to a 12-h light/dark cycle and food was available only in the dark period. Prior to exposure, rats in the (E)xercise group were required to execute five rotations of an activity wheel for a food pellet; wheel turns that occurred at times other than when a rat was feeding were recorded separately and labeled exercise running. In the (S)edentary and (A)nesthesia groups, wheel running was not possible and rats were required to execute five leverpresses for a single pellet. A compressed air-driven shock tube was used to expose rats to a supra-atmospheric wave of air pressure. The tube was separated into two sections by a polyester membrane, the thickness of which determined peak and duration of overpressure. All rats were anesthetized with 50 mg/kg of phenobarbital. After reaching a deep plane of anesthesia, they were individually tied in a stockinet across one end of the shock tube. In preliminary tests, the membrane thickness was 1000 (A)ngstroms and rats in Group L(ethality) were exposed to a 129 kPa (peak amplitude) wave of overpressure. Three of six rats survived exposure to this peak pressure; pathology was evident in the lungs and gastrointestinal tract of all non-survivors. Rats in Groups E and S were tested with a 500 A membrane, which resulted in an 83 kPa peak amplitude. All rats survived exposure to this lower peak pressure. On the day of exposure to blast, the relative reduction of intake during the first 3 h of the dark period was significantly greater for Group E than for Groups S and A; the intake of Groups E and S remained reduced for four additional recovery days. Bodyweight was not significantly affected. Exercise wheel running also was reduced significantly on the day of exposure and during subsequent recovery days. These preliminary findings suggest that exposure to sublethal blast overpressure can reduce food consumption and exercise performance, perhaps as a consequence of damage to the gastrointestinal tract and lungs.

The effects of wheel running, a light/dark cycle, and the instrumental cost of food on the intake of food in a closed economy.

The effects of wheel running on the food intake of rats, and on the extent to which rats defend their daily food intake against increases in the instrumental cost of food, were studied in a closed economy. Rats lived in cages that were attached to running wheels. Within each cage, water was freely available and lever pressing was required for access to food; a fixed number of presses was required for the delivery of a single food pellet. All cages were located in an environmental chamber where a 12-h light/dark cycle was continuously maintained. During stage I, the entrance to each running wheel was blocked and two series (series 1 and 2) of progressively increasing fixed ratios (FRs) of presses per pellet were imposed. Each FR was used for a single day. During stage II, the entrance to each wheel was unblocked and wheel running and food intake were allowed to stabilize. During stage III, the running wheels remained available and the FR was again increased (series 3). In stage I, increases in the FR reduced food intake proportionally more rapidly during the light than during the dark, and this reduction in the light was greater during series 1 than series 2. During stage II, food intake was transiently reduced during the first week of access to running wheels, but recovered by the end of the second week. During stage III, increases in the FR again reduced food intake proportionally more rapidly during the light than during the dark. Wheel running did not affect the extent to which food intake was reduced within light and dark periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic stress and time of day on preference for sucrose.

Rats were allowed to lever press for two types of food pellets of equivalent caloric value and total carbohydrate content. One type of food pellet provided more of the calories as sucrose. During a 16-day prestress period, lever presses for 12 rats were recorded hourly. Following the baseline period, four rats (stressed group) were shaped to pull a ceiling chain to avoid or escape signalled foot shock presented intermittently around-the-clock. Four additional rats (yoked group) were each paired to one of the chain-pulling rats such that the rat trained to pull the ceiling chain controlled stressor termination for both rats. A third group of four rats served as the control group and received no shock. We have previously reported that rats in this model of chronic stress tolerate the paradigm well, continuing to gain weight, eat, drink water, and groom and escape more than 99% of the trials presented. During the baseline period, the sweeter pellet was preferred by most rats, but differences in preference among rats and in preference at different times of day were observed. The preference for the high-sucrose pellet was most marked in the hours preceding lights off. Overall, no changes in food preference were seen as a function of stress condition during the 14-day stress period, although one rat in the yoked group increased preference for the sweeter pellet during stress and returned to prestress food preferences when stress was terminated.

Circadian effects of escapable and inescapable shock on the food intake and wheelrunning of rats.

The feeding and running activities of rats were used to characterize the stressful effects of footshock. A 12-hour light/dark cycle was continuously in effect. During the preshock stage, all rats lived in individual cages where they could drink water, press a lever once for each 45 mg food pellet or run in an attached running wheel. During the shock stage, rats were moved to cages where they could drink and eat, but not run. Five s of light followed by 5 s of a light + tone compound preceded five progressively more intense shock levels. Rats in group AE were trained to pull a ceiling chain to avoid/escape from footshocks that were scheduled 24 hours per day. In group YS, the frequency, intensity and pattern of shocks for a rat were yoked to a rat in group AE. Rats in group CN were not shocked. During recovery, rats were allowed to resume running. During the dark, but not the light of the first day of shock, the intake of groups AE and YS was less than the intake of group CN. By the third day of shock, the food intake of group AE recovered and was no longer different from the intake of group CN. Intake of group YS remained less than the intakes of groups AE and CN during the remainder of the shock stage. When shock was terminated, the intake of the YS group recovered, but neither running nor food intake differed among groups. These results suggest that although inescapable shock disrupts food intake more than escapable shock, this disruption is specific to the duration of the shock stage and depends on rat's circadian pattern of intake.

Time cost of alternation reduced demand for food in a closed economy.

A principal purpose of the present study was to characterize rats' demand for food by increasing the required delay between the alternation of leverpresses. While living in cages that were exposed to a 12:12 light:dark cycle, rats were required to alternate leverpresses for their entire daily food ration. After a press on one lever resulted in the delivery of a food pellet, a red cuelight was illuminated for a fixed duration that equaled the imposed delay between successive leverpresses. After the imposed delay elapsed and the cuelight was turned off, a press on the alternate lever resulted in the delivery of another food pellet. Increases in the imposed delay from 0.01 s to 16 s reduced mean percent correct (alternation) and mean food intake, although both were reduced more rapidly and to a greater extent in the light than in the dark photoperiod. This interaction resulted from a reduction of meal size in the light and a compensatory increase in meal size in the dark as the imposed delay increased. Rats also defended their daily intake in the dark against increasingly larger imposed delays by spending increasingly larger amounts of time alternating and by increasing total (correct + incorrect) presses. These results suggest that photoperiod is a determinant of the motivational value of food as a reinforcer for instrumental behavior in a closed economy.

Effects of sustained avoidance/escape on demand for food.

Rats were concurrently exposed to a sustained avoidance/escape (SAE) procedure and a procedure for assessing demand for food. In the sustained SAE procedure, signalled shock avoidance/escape trials were presented at varying intervals averaging five minutes. The shock could be avoided by pulling on a ceiling chain early in the trial, or escaped by pulling on the chain later in the trial. Demand curves for food were generated by requiring 1, 5, 10, 20, 40, 80, 160, and 320 lever presses for each food pellet on successive days. The demand curve procedure was introduced after either brief (3 or 5 days) or extended (21 or 23 days) exposure to SAE. Following brief exposure to SAE, SAE animals showed decreased food intake and less elasticity of demand relative to non-SAE controls. Following extended exposure to SAE, these effects were diminished or absent.

The effects of alpha-alpha cross-linked hemoglobin on the feeding and locomotor activity of rats.

The feeding and locomotor activities of rats were used as an assay for the potentially toxic effects of an oxygen-carrying blood substitute. Rats lived in individual cages where they could feed ad lib by pressing a lever once for each small food pellet, drink water, or run in a wheel; a 12-h light/dark cycle was continuously in effect. After being anesthetized and hemorrhaged one-third of their total blood volume, individual rats were resuscitated with one of the following fluids: their own shed blood (OB), bis(3,5-dibromosalicylfumarate) alpha-alpha cross-linked hemoglobin (HbXL), human serum albumin (HSA), or Ringer's lactate (RL). Rats in a fifth group were not resuscitated (NR). During the dark period on the day of hemorrhage, the food intake and running activity of rats in all groups decreased. Food intake and locomotor activity of rats in the HbXL, NR and OB groups were more suppressed than the HSA or RL groups. The food intake of rats in the HbXL and NR groups remained significantly more suppressed during the dark period of the first recovery day; running continued to be suppressed in the HbXL group on the first recovery day, but not the second recovery day. In an effort to determine the extent to which the rats in the HbXL group were impaired, an increasing number of lever presses was required for each food pellet beginning with recovery day number 3 for all treatment groups. As the ratio of presses per pellet was increased, food intake decreased and running increased for all groups; no differences between groups were significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained stress disrupts the performance and acquisition of delayed alternation in rats.

The effects of sustained stress on acquisition and performance of a delayed alternation task were studied in male rats. Rats lived 24 h per day in operant cages where they earned all of their food via lever pressing. During the stress portion of each experiment, one group of rats was able to avoid or escape signaled intermittent footshock (Avoidance/Escape group), a second group (Yoked) did not have control over shock termination, a third group never received shock (Control). Shock trials were presented around-the-clock at approximately 5-min intervals and the stress portion of each study lasted 1 week. We have previously reported that rats tolerate this paradigm well and avoid/escape 99% of the shock trials. Three experiments were conducted. In Experiment 1, rats learned the delayed alternation task prior to stress onset; in Experiment 2, rats were exposed to stress and the alternation task concurrently; in Experiment 3, rats were stressed for 14 days prior to being required to perform the delayed alternation task. In the first experiment, stress decreased both food intake and the accuracy of responding during the first days of stress. In the second experiment (acquisition), stressed rats required more days to reach asymptotic performance on the alternation task. In Experiment 3, rats stressed for 14 days prior to acquisition of the delayed alternation task performed similarly to controls.

Effects of controllable vs. uncontrollable chronic stress on stress-responsive plasma hormones.

We have previously reported effects of chronic stress on circadian rhythms of temperature, eating, and locomotor activity. These studies were conducted using an around-the-clock signalled intermittent footshock paradigm in which some rats have control over shock termination while other rats are yoked to the rats with control. Although this paradigm is stressful, as suggested by decreases in food intake and disrupted circadian rhythms, rats tolerate the paradigm well, continuing to eat, drink, gain weight, and groom. In the present studies, rats were sacrificed following 3 or 14 days of stress, and plasma was collected for hormonal assays. After 3 days of stress, plasma corticosterone and prolactin levels were elevated in both stress groups compared to controls; yoked rats had higher levels of corticosterone than rats in the group with control over shock termination, while prolactin levels in both stressed groups were similar. ACTH levels were similar in stressed and control rats. After 14 days of stress, ACTH and corticosterone levels in both stress groups were similar to control levels. Prolactin levels were elevated in the yoked experimental group compared to levels in control or controllable stress groups. These data support previous studies suggesting that control over stressors attenuates the effects of stress on physiology and demonstrate that two hormones with diverse biological effects are elevated by chronic stress.

Sustained stress and fixed interval performance.

The effects of sustained stress on response rate and temporal patterning (quarter-life) of rats performing either a previously learned fixed-interval schedule (FI 60) or learning an FI 60 simultaneously with stress onset were determined. Rats lived 24 h/day in operant cages, where they earned all of their food via lever-pressing. During the stress portion of each experiment, one group of rats was able to avoid or escape signalled intermittent footshock (Avoidance/ Escape Group), a second group (Yoked) did not have control over shock termination, a third group never received shock (Control). Shock trials were presented around the clock at approximately 5-min intervals and the stress portion of each study lasted 1-2 weeks. We have previously reported that rats tolerate this paradigm well and avoid/escape 99% of the shock trials. In rats previously trained on the FI task, both rate of responding and quarter-life values were significantly decreased on the first day of stress for both the Avoidance/Escape and Yoked Groups. Food intakes and quarter-life values were not significantly different from the controls by stress Days 3 and 2, respectively. In the acquisition study, controls learned the F1 task by Day 4 as judged by quarter-life of responding. FI task acquisition was significantly impaired in stressed rats compared to controls, not reaching asymptotic performance until Day 9 of stress. There were no major differences between the 2 stress groups in either study. These data demonstrate that stress may impair both the rate and patterning of behavior, and suggest that this rodent paradigm may usefully model some aspects of the effects of stress in humans.

Effects of controllable vs. uncontrollable stress on circadian temperature rhythms.

The effects of sustained stress on body temperature were investigated in rats implanted with mini-transmitters that permitted remote measurement of body temperature. Temperature was first monitored during control conditions. Following the control period, rats were either shaped to avoid/escape signalled around-the-clock intermittent footshock (controllable stress) or yoked to the controlling rats such that the controlling rat and the yoked rat received shock of the same duration, but only the controlling rat could terminate shock by pulling a ceiling chain. Under control conditions, rats demonstrated regular rhythms in body temperature which averaged 1 degree higher during the 12-h dark cycle than the light cycle. Stress disrupted the rhythm and markedly decreased the night-day difference in temperature, especially in the yoked rats in which almost no difference between light and dark cycle temperature was seen. The disruption was most marked for the first days of stress. A regular temperature rhythm was reestablished following about 5 days of stress although the stress condition continued. Leverpressing for food was also affected by the stress conditions with both stress groups leverpressing less than controls and the uncontrollable stress group pressing less than the controllable stress group. These data offer additional evidence of the increased pathophysiological effects of uncontrollable as compared to controllable stress.

Effects of chronic stress on sleep in rats.

The present study was conducted to determine the effects of chronic stress on sleep using a rodent paradigm of around-the-clock signalled intermittent foot shock in which some rats can pull a chain to avoid/escape shock while another group of rats is yoked to the first group. We measured sleep using telemetry; four-channel EEG was collected 24 h/day in rats during 2 prestress days; days 1, 2, 3, 7, and 14 during chronic stress; and 3 poststress days. States of REM sleep, non-REM (NREM) sleep, and waking were scored for each 15-s period of the EEG recordings. During the prestress period, rats slept (REM plus NREM) 55% of available time during the light hours and 34% of the dark hours with the remainder represented by waking. On the first day of stress, total sleep and, especially REM sleep, decreased markedly. By the second day of stress, only REM sleep in the controllable stress group (but not the uncontrollable stress group) was still significantly decreased compared to prestress levels, and REM sleep returned to baseline levels by day 7 of stress. The recovery of sleep quantity was accomplished by increased sleep during the dark hours, resulting in a long-lasting disruption of normal circadian sleep patterning.