Bi-directional changes in fractional anisotropy after experiment TBI: Disorganization and reorganization?

The current dogma to explain the extent of injury-related changes following rodent controlled cortical impact (CCI) injury is a focal injury with limited axonal pathology. However, there is in fact good, published histologic evidence to suggest that axonal injury is far more widespread in this model than generally thought. One possibility that might help to explain this is the often-used region-of-interest data analysis approach taken by experimental traumatic brain injury (TBI) diffusion tensor imaging (DTI) or histologic studies that might miss more widespread damage, when compared to the whole brain, statistically robust method of tract-based analysis used more routinely in clinical research. To determine the extent of DTI changes in this model, we acquired in vivo DTI data before and at 1 and 4weeks after CCI injury in 17 adult male rats and analyzed parametric maps of fractional anisotropy (FA), axial, radial, and mean diffusivity (AD, RD, MD), tensor mode (MO), and fiber tract density (FTD) using tract-based spatial statistics. Contusion volume was used as a surrogate marker of injury severity and as a covariate for investigating severity dependence of the data. Mean fiber tract length was also computed from seeds in the cortical spinal tract regions. In parallel experiments (n=3-5/group), we investigated corpus callosum neurofilaments and demyelination using immunohistochemistry (IHC) at 3days and 6weeks, callosal tract patency using dual-label retrograde tract tracing at 5weeks, and the contribution of gliosis to DTI parameter maps using GFAP IHC at 4weeks post-injury. The data show widespread ipsilateral regions of significantly reduced FA at 1week post-injury, driven by temporally changing values of AD, RD, and MD that persist to 4weeks. Demyelination, retrograde label tract loss, and reductions in MO (tract degeneration) and FTD were shown to underpin these data. Significant FA increases occurred in subcortical and corticospinal tract regions that were spatially distinct from regions of FA decrease, grossly affected gliotic areas, and MO changes. However, there was good spatial correspondence between regions of increased FA and areas of increased FTD and mean fiber length. We discuss these widespread changes in DTI parameters in terms of axonal degeneration and potential reorganization, with reference to a resting state fMRI companion paper (Harris et al., 2016, Exp. Neurol. 227:124-138) that demonstrated altered functional connectivity data acquired from the same rats used in this study.

Traumatic brain injury results in disparate regions of chondroitin sulfate proteoglycan expression that are temporally limited.

Axonal injury is a major hallmark of traumatic brain injury (TBI), and it seems likely that therapies directed toward enhancing axon repair could potentially improve functional outcomes. One potential target is chondroitin sulfate proteoglycans (CSPGs), which are major axon growth inhibitory molecules that are generally, but not always, up-regulated after central nervous system injury. The current study was designed to determine temporal changes in cerebral cortical mRNA or protein expression levels of CSPGs and to determine their regional localization and cellular association by using immunohistochemistry in a controlled cortical impact model of TBI. The results showed significant increases in versican mRNA at 4 and 14 days after TBI but no change in neurocan, aggrecan, or phosphacan. Semiquantitative Western blot (WB) analysis of cortical CSPG protein expression revealed a significant ipsilateral decrease of all CSPGs at 1 day after TBI. Lower CSPG protein levels were sustained until at least 14 days, after which the levels began to normalize. Immunohistochemistry data confirm previous reports of regional increases in CSPG proteins after CNS injury, seen primarily within the developing glial scar after TBI, but also corroborate the WB data by revealing wide areas of pericontusional tissue that are deficient in both extracellular and perineuronal net-associated CSPGs. Given the evidence that CSPGs are largely inhibitory to axonal growth, we interpret these data to indicate a potential for regional spontaneous plasticity after TBI. If this were the case, the gradual normalization of CSPG proteins over time postinjury would suggest that this may be temporally as well as regionally limited.

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats.

Prior work has shown that d-amphetamine (AMPH) treatment or voluntary exercise improves cognitive functions after traumatic brain injury (TBI). In addition, voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF). The current study was conducted to determine how AMPH and exercise treatments, either alone or in combination, affect molecular events that may underlie recovery following controlled cortical impact (CCI) injury in rats. We also determined if these treatments reduced injury-induced oxidative stress. Following a CCI or sham injury, rats received AMPH (1 mg/kg/day) or saline treatment via an ALZET pump and were housed with or without access to a running wheel for 7 days. CCI rats ran significantly less than sham controls, but exercise level was not altered by drug treatment. On day 7 the hippocampus ipsilateral to injury was harvested and BDNF, synapsin I and phosphorylated (P) -synapsin I proteins were quantified. Exercise or AMPH alone significantly increased BDNF protein in sham and CCI rats, but this effect was lost with the combined treatment. In sham-injured rats synapsin I increased significantly after AMPH or exercise, but did not increase after combined treatment. Synapsin levels, including the P-synapsin/total synapsin ratio, were reduced from sham controls in the saline-treated CCI groups, with or without exercise. AMPH treatment significantly increased the P-synapsin/total synapsin ratio after CCI, an effect that was attenuated by combining AMPH with exercise. Exercise or AMPH treatment alone significantly decreased hippocampal carbonyl groups on oxidized proteins in the CCI rats, compared with saline-treated sedentary counterparts, but this reduction in a marker of oxidative stress was not found with the combination of exercise and AMPH treatment. These results indicate that, whereas exercise or AMPH treatment alone may induce plasticity and reduce oxidative stress after TBI, combining these treatments may cancel each other's therapeutic effects.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

Effects of fetal forebrain transplants in ibotenic-injured nucleus basalis: an anatomical investigation.

Survival of fetal basal forebrain transplant (TP) into ibotenic-injured nucleus basalis of rats was examined after a delay lesion and TP (1 or 2 weeks) and a delay between harvest and TP (1-4.5 hours). Optimal TP survival occurred for TP made 2 weeks postlesion and less than 2 hours after harvesting. In these cases large, healthy TP-neurons displayed robust cytochrome oxidase (CO) activity and sent cholinergic processes throughout the TP and occasionally into host tissue. A mild astrocytic reaction was observed within the TP and at the host-TP interface. Surviving TPs increased choline acetyltransferase innervation and CO activity within the ipsilateral frontoparietal cortex. Therefore data suggest that fetal cholinergic TPs into the damaged NBM reduced neuronal degeneration within the NBM and stimulated remaining neurons spared by the lesion.

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.

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.

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.