Biomedical subjects

R L Sutton

Publications and source records attributed to R L Sutton.

At least 19 recordsLinked to original sources

PubMed2001

Behavioral and morphological consequences of primary astrocytes transplanted into the rat cortex immediately after nucleus basalis ibotenic lesion.

Adult male rats received transplants of dissociated 30-day old cultured cortical astrocytes into the ipsilateral frontal and parietal cortex immediately after unilateral ibotenic acid lesion of the NBM or after sham injury. We hypothesized that transplants of astrocytes into the acetylcholine-deprived cortex might provide trophic support to terminals arising from damaged NBM neurons. Twenty four hours after transplantation and every other day for 11 days post surgery, the animals were tested for locomotion and habituation in an open field. NBM lesion reduced vertical movements only as compared to no lesion and no transplant counterparts. Nine days after surgery rats with NBM lesion and astrocyte-transplants into the cortex were as impaired in the acquisition of a passive avoidance (PA) task as untreated counterparts. Animals with no lesions and transplants into the cortex also had significant PA acquisition deficits. All rats with ibotenic lesion were significantly impaired on PA retention as compared to rats with no lesions. Astrocyte-transplants survived up to 2 months after cortical implantation but these transplants produced severe laminar disruption and gliosis. This effect was greater in rats with NBM lesion than in intact animals with transplants into the cortex. These data show that astrocyte-transplants do not promote functional recovery after NBM lesion and suggest an immune rejection of the astrocyte transplants by the host brain.

Acetylcholine↗

PubMed2001

Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients.

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.

Adolescent↗

PubMed2000

Alleviation of brain injury-induced cerebral metabolic depression by amphetamine: a cytochrome oxidase histochemistry study.

Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and the administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of 11 subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilateral to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans.

Amphetamine↗

PubMed1999

Inhibition of microglial cell RANTES production by IL-10 and TGF-beta.

Using human fetal microglial cell cultures, we found that the gram-negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)-kappaB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha dose-dependently stimulated microglial cell RANTES production via NF-kappaB activation. Anti-inflammatory cytokines, IL-10, and transforming growth factor (TGF)-beta sequentially inhibited LPS- and cytokine-induced microglial cell NF-kappaB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti-inflammatory cytokines IL-10 and TGF-beta down-regulate the production of this beta-chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain.

Cell Lineage↗

PubMed1999

The effects of acute and chronic alcohol ingestion on outcome following multiple episodes of mild traumatic brain injury in rats.

OBJECTIVE: Recent studies suggest that in some circumstances, alcohol intoxication at the time of severe head injury may be neuroprotective. The objective of this study was to determine the effect of acute and chronic alcohol ingestion on outcome in rodents sustaining multiple episodes of mild traumatic brain injury while intoxicated. METHOD: For two weeks before experimentation, adult male Sprague-Dawley rats received intoxicating levels of 95% ethanol (3 g/kg) or normal saline (NS) every other day by orogastric instillation. On the day of experimentation, the animals were randomized to receive alcohol or NS. Two hours later, the animals received either mild (1.2 +/- 0.4 ATA) fluid percussion injury (FPI) or no injury. The injured animals received a total of three episodes of FPI (once every four days). Mean reflex recovery time (RRT) was determined (seconds +/- SEM) immediately after each episode. Mean latency time (seconds +/- SEM) for Morris Water Maze (MWM) performance was assessed at post-trauma days 11-19. RESULTS: The chronic alcohol-exposed (CA) and the non-alcohol-exposed (NA) animals intoxicated when injured had prolonged escape, righting, and corneal RRTs after each FPI compared with the nonintoxicated injured animals and the non-injured shams. However, the CA animals had significantly shorter RRTs when compared with the NA rats. All the injured animals had MWM deficits on testing days 1-6 compared with the noninjured controls. On the last two MWM testing days, the injured NA animals had significantly better MWM performance than the injured CA rats. CONCLUSIONS: The injured intoxicated CA animals had a more rapid recovery of reflexes compared with the injured intoxicated NA animals. Despite initial MWM deficits, the injured NA rodents eventually began to learn the MWM. The injured CA rats never learned the maze. Under the conditions of this study, acute alcohol intoxication at the time of multiple episodes of minor head trauma did not provide neuroprotection for NA or CA rodents.

Acute Disease↗

PubMed1999

Hyperosmosis of cerebral injury.

Changes in tissue osmolarity or cerebrospinal fluid osmolarity after cerebral injury have received little attention in the literature, but osmosis may be an important cause of early cerebral edema. This paper reviews concepts and terms relating to osmosis, and reviews the few papers in the literature which have studied osmolarity after cerebral injury. In studies of both traumatic brain injury and ischemia, tissue osmolarity is elevated. Osmolarity of cerebrospinal fluid has also been shown to increase with injury. There have been no human studies examining osmolarity of tissue or cerebrospinal fluid after cerebral injury. Theoretical implications of the osmotic gradient are discussed.

Animals↗

PubMed1998

Cytokine regulation of human microglial cell IL-8 production.

IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1 beta, or to TNF-alpha, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-beta 1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.

Age Factors↗

PubMed1998

Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions.

Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a battery of behavioral tests to determine if different impact sites produce different patterns of behavioral deficits and to determine how long behavioral deficits can be detected after TBI. Prior to surgery, rats were trained to criteria on delayed nonmatching to position, radial arm maze, and rotarod tasks. Rats received sham surgery (controls), midline frontal contusions (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout the next 12 months. Cognitive deficits were more robust and more enduring than sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI rats exhibited transient deficits in the forelimb placing and in the rotarod test of motor/ambulatory function, but cognitive deficits were apparent throughout the 12-month postsurgery period on tests of spatial learning and memory including: (1)reacquisition of a working memory version of the radial arm maze 6-7 months post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3) repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal TBI rats exhibited a different pattern of deficits, with the most robust deficits in tests of attention/orientation such as: (1) the delayed nonmatching to position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated acquisition version of the water maze--especially on the first "information" trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5 months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11 months after surgery. These results suggest that long-term behavioral deficits can be detected in rodent models of TBI, that cognitive deficits seem to be more robust than sensorimotor deficits, and that different TBI impact sites produce dissociable patterns of cognitive deficits in rats.

Animals↗

PubMed1995

Effects of unilateral entorhinal cortex lesion and ganglioside GM1 treatment on performance in a novel water maze task.

Transient deficits have been reported after unilateral entorhinal cortex (EC) lesion. To determine whether there is a more persistent deficit, adult male Sprague-Dawley rats with electrolytic or sham lesions of the left entorhinal cortex were examined on acquisition of a modified working memory task in the Morris water maze. This delayed matching-to-sample task, with a 1-h intertrial interval, reveals a significant deficit in total distance to platform in both presentation (Trial 1) and matching (Trial 2) in the rats with entorhinal lesions. We have also found that this test can be used to assess significant deficits in perseveration (repeated nonproductive movement) in rats with entorhinal lesions. The deficits can be seen up to 16 days postinjury. Administration of ganglioside GM1 resulted in a moderate improvement in performance in both water maze measures analyzed. All groups (sham operated, lesion with saline treatment, and lesion with ganglioside GM1 treatment) were given three other tests, which were used to evaluate possible contributing factors to deficient water maze performance. A one-trial test for exploration of novel objects revealed no significant, simple working memory deficit in any group. Plus maze testing, to assess possible differences in levels of anxiety or increased activity as a component of water maze performance, also revealed no differences in the three groups. All groups were also similar in motor activity, shown by monitoring of activity levels. The worsened water maze performance observed in rats with EC lesion may be related to deficits in working memory ability within the framework of acquisition of a more complex spatial learning task.

Animals↗

PubMed1994

A longitudinal study of injury morbidity in an African-American population.

OBJECTIVE: To improve understanding of the patterns of injury morbidity and mortality in an urban African-American population. DESIGN: Prospective survey of emergency department records for a geographically defined population from 1987 through 1990. SETTING: Eleven hospital emergency departments in Philadelphia, Pa. PARTICIPANTS: The approximately 68,000 people living in 17 census tracts in western Philadelphia. RESULTS: A total of 46,260 injury events were identified in the survey (168.8 events per 1000 population annually). Half of the population made an emergency department visit for one or more injuries during the 4 years of study. There were 2796 hospital admissions (10.2/1000 population) and 403 deaths (1.5/1000 population) as a result of these injuries. Although in 1987 falls were the most frequent type of injury resulting in an emergency department visit, by 1989 the number of interpersonal intentional injury events exceeded the number of falls. Interpersonal intentional injuries accounted for 31.2% of hospital admissions and 42.7% of deaths. Of men 20 through 29 years old, 94.3% visited an emergency department at least once in the 4 years because of an injury, and 40.9% of men in this age group sought treatment for one or more interpersonal intentional injuries. The likelihood of future interpersonal intentional injury-related visits increased with the number of previous injuries of this type. CONCLUSIONS: Interpersonal intentional injury occurs frequently in this population. More attention needs to be paid to prevention and intervention to reduce the toll of this violence. The high prevalence of injury in certain age strata may make general, population-based efforts for injury prevention more efficient than efforts targeted to subgroups.

Accidental Falls↗

PubMed1994

Metabolic changes following cortical contusion: relationships to edema and morphological changes.

Rats with contusion injury to the right cortex exhibited significant formation of edema 6 and 24 hours after injury which resolved by 8 days and was replaced by cavitation necrosis. The contusions produced hyperglycolysis and ischemia in the impacted cortical tissue and underlying hippocampus immediately through 30 minutes post-injury. Glucose utilization was depressed throughout the contused cortex and in ipsilateral subcortical regions, as was blood flow, at chronic (1 and 10 days) periods after injury.

Animals↗

PubMed1994

Spontaneous and amphetamine-evoked release of cerebellar noradrenaline after sensorimotor cortex contusion: an in vivo microdialysis study in the awake rat.

Microdialysis sampling combined with HPLC was used to assess spontaneous and d-amphetamine (AMPH)-evoked release of noradrenaline (NA) in the cerebellum 1 day after probe implantation and 1 day after contusion of the right sensorimotor cortex (SMCX) in rats. In normal controls the mean +/- SEM basal NA release was 10.08 +/- 0.97 pg in the left cerebellar hemisphere and 8.21 +/- 1.17 pg in the right hemisphere 22-24 h after probe implantation. The average +/- SEM NA release in a 3-h period after administration of AMPH (2 mg/kg, i.p.) increased to 453 +/- 47.35 pg in the left and to 402 +/- 49.95 pg in the right cerebellar hemisphere. NA release (range of 413-951% increase over baseline) was maximal 20-40 min postdrug, returned to basal levels within 5 h, and remained unchanged for the 22-24-h postdrug measurement period. Animals with a focal SMCX contusion had a marked depression of both spontaneous and AMPH-evoked NA release. Mean +/- SEM basal NA release was 4.84 +/- 1.09 pg in the left and 4.95 +/- 0.43 pg in the right cerebellar hemisphere from 22 to 24 h postinjury, with NA levels increasing to 259 +/- 75.44 and 219 +/- 23.45 pg in the respective hemispheres over a 3-h period after AMPH. The maximal AMPH-induced increase in NA release ranged from 522 to 1,088% of basal levels in contused rats, with NA release returning to predrug levels within 5 h and remaining depressed for at least 48 h postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1993

Unilateral cortical contusion injury in the rat: vascular disruption and temporal development of cortical necrosis.

Cerebrovascular disruption and cortical pathology resulting from either moderate (M-TBI) or severe (S-TBI) traumatic brain injury produced by a pneumatically-driven cortical contusion device were assessed in adult male rats sacrificed at 6 and 24 h or 8 and 30 days after injury to the right sensorimotor cortex. Epidural, subdural, subarachnoid, petechial (cortex and corpus callosum), and/or intraventricular hemorrhage was present in all animals, more extensively and severely following S-TBI. At 6 or 24 h after TBI, acidophilic (acid fuchsin-positive) neurons were numerous and widespread (S-TBI > M-TBI) in the ipsilateral contused cortex. By 8 days few acidophilic neurons were present in peri-impact regions of the ipsilateral neocortex, and none were detected in cortex 30 days postinjury. Both M-TBI and S-TBI groups had enlarged ipsilateral cortical volumes (edema) at 6 and 24 h post-contusion. Eight and 30 days after injury the mean volume of cortical necrosis was significantly larger in S-TBI than in M-TBI rats, and cortical necrosis in both TBI conditions increased between 8 to 30 days postinjury. These results indicate that this pneumatically-driven contusion device produces reliable and consistent primary and secondary cortical histopathology, the extent of which is related to the severity of initial injury.

Animals↗

PubMed1993

An injury prevention program in an urban African-American community.

OBJECTIVES: Injury is a major US public health problem, particularly in urban minority communities. This paper evaluates the impact of the Safe Block Project, a comprehensive injury prevention trial, on home hazards and injury prevention knowledge in a poor urban African-American community. METHODS: Nine census tracts in the community were allocated to either the intervention area or the control area. The intervention, carried out by trained community outreach workers, consisted of (1) home modification for simple prevention measures, (2) home inspection accompanied by information about home hazards, and (3) education about selected injury prevention practices. Approximately 12 months after the intervention, random samples of control and intervention homes were assessed for home hazards and injury prevention knowledge. RESULTS: A significantly larger proportion of intervention homes than control homes had functioning smoke detectors, syrup of ipecac, safely stored medications, and reduced electrical and tripping hazards. No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct. CONCLUSIONS: There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct. The Safe Block Project could serve as a model for future urban injury prevention efforts.

Accidents, Home↗

PubMed1992

Critical cooling rates for aqueous cryoprotectants in the presence of sugars and polysaccharides.

The technique of isothermal emulsion differential scanning calorimetry was used to determine time-temperature-transformation (TTT) curves for aqueous glycerol and butane-2,3-diol in the presence of various polysaccharides and sugars. The critical cooling rate required to avoid the crystallization of ice in these solutions was then calculated from the experimental TTT curves. The polysaccharides used in this study included starch hydrolysis products and dextrans of various molecular weights. The sugars used here were sucrose, glucose, trehalose, and raffinose. The results show that the critical cooling rates of butane-2,3-diol and glycerol are reduced by varying amounts by the addition of such materials but that the reduction is not as great as is achieved by the addition of polyethylene glycol with a molecular weight of 400.

Butylene Glycols↗

PubMed1992

Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study.

The maturation of brain oxidative capacity was studied in kittens, using cytochrome oxidase histochemistry, at different ages throughout development. Optical densitometry values of reacted tissue were obtained for 50 different structures of the brain. In general, most structures reached adult levels of oxidative capacity by 30 days of age with some motor areas (e.g., cerebellum, red nucleus) exhibiting adult values as early as 7 days of age. Thereafter, some structures (e.g., basal ganglia, thalamus) exhibited levels of cytochrome oxidase activity that exceeded adult values for varying periods of time. These findings indicate regional heterogeneity in the maturation of cerebral oxidative capacity. Furthermore, these maturational patterns appear to correlate well with previous observations from anatomical, physiological and neurobehavioral studies.

Animals↗

PubMed1991

A population-based study of injuries in inner-city women.

Although injuries are the number one cause of death for women under age 45 years in the United States, very little is known about nonfatal injuries to women, particularly those from urban, black communities. The Philadelphia Injury Prevention Program is a surveillance system of fatal and nonfatal injuries in a poor, urban, black community in western Philadelphia, Pennsylvania. Nearly 10% of the estimated population of 31,032 women aged 15 years and older suffered an injury resulting in an emergency room visit or death during the 1-year study period from March 1, 1987 through February 29, 1988. The major causes of injury were falls (25.1 per 1,000 women), violence (20.8 per 1,000 women), and motor vehicle incidents (16.8 per 1,000 women). Violence was the leading cause of injury for women aged 15-44 years and the most common cause of injuries among women with two or more injuries during the 1-year period. Injury rates were highest for women aged 25-34 years (157.1 per 1,000 women); nearly 16% of the population in this age group suffered an injury resulting in an emergency room visit or death during the 1-year study period. Rates declined with advancing age for each injury type except for falls; which were most common in young women aged 25-34 years (28.4 per 1,000 women) and in the aged 65 years and older (29.0 per 1,000 women). We conclude that in his population, injuries to young women appear to be a major public health problem. More work is needed to understand the nature of injuries occurring to young women in urban communities.

Accidental Falls↗

PubMed1991

The prediction of water activities in multicomponent systems.

The molecular bases of the equilibrium water activity concept are discussed and illustrated using some simplified examples. It is shown, using a relatively refined treatment, that at the moment we are not in a position to predict water activities, even for simple systems. A method is described which allows the prediction of the water activity of multicomponent systems from the properties of solutions containing one and two solutes. The method can also be used to predict solubilities in systems containing more than one solute, and this is illustrated with an example.

Chemical Phenomena↗