Objective(s): Melatonin is known as an anti‐inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death apoptosisin several models of braininjury. Secondary injury following the primary traumaticbraininjury TB) results in glial cells activation, especially astrocytes. )n fact, astrocyte activation causes the production of pro‐inflammatory cytokines that may lead to secondary injury. Since most TB) research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation astrogliosis , as well as inhibition of apoptosisinbrain tissue of male rats after TB).
that the rate of complications between the groups (normo- thermia and hypothermia) was not significantly different. Hypothermia group demonstrates markedly reduced ICP and inhibited hyperglycemia. The duration of TH is impor- tant in both preclinical and clinical TBI investigation. Jiang et al. reported the correlation of hypothermic duration and behavioral outcome after severe TBI. They conclude that patients underwent cooling for ive days demonstrated better behavioral outcomes than those patients underwent three days. Tokutomi et al. reported that temperature control of 35-35.5˚C is sufficient to control intracranial hyperten- sion without inducing cardiac dysfunction. Although it is not clear the mechanisms responsible for the actions of hypothermia in the treatment of TBI, mild degree TH have a reliable association with the expression of commexin-43 and glutamate-transporter-1 in the hippocampus following TBI inrats. TH also improved brain edema induced by TBI and neurologic deicit. It seems accompanied by decreasing in expression of connexin-43, increased after TBI in normal condition. In accordance with previous studies, a model of luid percussion injury, post-traumatic hypothermia sig- niicantly attenuated cell death within the hippocampus and attenuated caspase-3 upregulation, thereby reducing mark- ers of apoptosis.
This therapeutic concentration is achieved by a loading dose (as low as 10 mg/kg) followed by maintenance doses (as high as 60 mg/kg). In rodents, an i.p. dose of 200 mg/kg gives rise to a peak serum concentration of 400 m g/ml 15 minutes post injection that rapidly decreases to about 40 m g/ml by 8 hr post-infusion . In contrast, an injection of 400 mg/kg gives rise to a plasma concentration of approximately 150 m g/ml at 8 hr. A number of studies have utilized 300 mg/kg or 400 mg/kg and have observed HDAC and/or GSK-3 inhibition in the brainand other organs [8,51–53]. Consistent with these studies, we found that 400 mg/kg VPA significantly increased histone acetylation, and reduced b- catenin phosphorylation in hippocampal tissue extracts (Figure 1). Using a dose of 400 mg/kg, we observed that VPA improved motor function, and enhanced spatial learning and memory. Although the VPA-treated animals displayed a quadrant prefer- ence when assessed in a 24 hr probe trial, post-hoc analysis revealed that this difference was due to a preference for the target quadrant (I) relative to only the starting quadrant (III). This implies that although the VPA-treated, injured animals have better long-term memory for the platform position than do vehicle- treated injured animals, the performance of neither group was to the level typically observed for uninjured animals The improve- ment in motor and cognitive performance seen after acute VPA treatment suggests that this compound may reduce TBI-associated neuronal degeneration. Previous studies have reported that valproate can be neuroprotective, both for cells grown in culture and as well as in a rodent models of status epilepticus and ischemic stroke [42,43,52]. For example, Ren et al reported that treatment of ratswith 300 mg/kg valproate following middle cerebral artery occlusion (MCAO) significantly reduced infarct size and improved neurologic recovery . Consistent with this, our measurement of cortical contusion
in vivo studies. For example, it has been demonstrated that wogonin suppresses lipopolysaccharide (LPS)-induced production of nitric oxide (NO), prostaglandin E2, and pro-inflammatory cytokines in immune cells such as macrophages and microglial cells [10–12] andreduces migration in microglial cells via inhibition of NF-kB activity . In addition, treatmentwith wogonin was found to alleviate inflammatory responses caused by skin inflammation and carrageenan-induced hindpaw edema in animal studies [14,15]. Increasing evidence suggests that wogonin may have neuropro- tective effects in the injured brain. Wogonin attenuated the death of hippocampal neurons and inhibited microglia activation in global ischemia and excitotoxic injury models . Furthermore, wogonin also reduced early ischemic braininjuryand improved acute behavioral dysfunctions caused by focal cerebral ischemia [16,17]. In addition, wogonin attenuated excitotoxic and oxidative stress-induced neuronal damage in primary cultured rat cortical cells  and reduced neuronal damage caused by exposure to oxygen and glucose deprivation in cultured rat hippocampal slices . Despite evidence indicating the benefits of wogonin treatment to early neurological recovery in stroke models, there is a lack of data describing the long-term effects of wogonin on functional recovery or cell survival in the injured brain. In particular, the neuroprotective effects of wogonin on TBI have not been established.
We further detected the apoptosis protein expression with HBO treated brain samples. The protein expression tendency is similar to TBI brain without HBOT (Figure 2), but several subtle changes were noticed: first, a stronger Bcl-2 band was detected in HBOT group at time point 1d, which was barely visible in the corresponding TBI sample; second, the increase of Bax expression was less apparent in HBOT group; third, the cleaved Caspase-3 band was more significantly reduced in HBOT group at time point 7d (Figure 4A). These results suggested that HBOT effectively blocked neural apoptosis pathways. We then measured c-fos and c-jun mRNA level, as expected, HBOT significantly reduced their expression which were most evident at 1d post injury, suggesting an early effective window for HBO treatment (Figure 4B-C).
Abstract – Objective: To evaluate the efficiency of selective hypothermia in the treatment of the traumaticbraininjuryinrats. Method: After the trauma produced for the model of cortical impact, a small craniectomy in the right frontoparietal region was carried through; after the procedure the animals had been divided in two groups of 15 each. Group A, without treatmentwith hypothermia (control group) and group B, treated with selective hypothermia for a period to 5 to 6 hours. After this time all the animals were sacrificed, their brains had been removed and histopathological analysis was carried through. Results: Comparison between both groups was done using the counting of neurons injured for field. Counting in the control group n=15 had an average of 70.80 neurons injured for field against an average of 21.33 neurons injured for field in group B (submitted to the treatmentwith hypothermia), with n=15 also. The difference was statiscally significant. Conclusion: Based in the quantification of the neurons injured for field, the effectiveness of the treatmentwith selective hypothermia was demonstrated.
Cortical brain tissue samples were harvested, and protein and RNA extraction were done using mirVana PARIS Kit (Ambion) according to the manufacturer’s instructions. Protein content was determined by the BCA protein assay kit (Novagen) using bovine serum albumin (BSA) as a standard. 20 m g protein lysate was mixed with 4x Sample Loading Buffer (Biorad) and 20x Reducing Agent (Biorad) heated for 5 minutes at 95 uC and separated by SDS-PAGE in 12% Criterion XT Bis-Tris precast gels (Biorad). After transfer (1 hr, 40V) to a nitrocellulose membrane (What- man), membranes were blocked (StartingBlock T20 blocking buffer, Thermo Scientific) for 15 minutes at room temperature and incubated overnight at 4uC with 0.2 m g/ml polyclonal rabbit anti-myelin-basic-protein antibody (Genscript). Membranes were rinsed again with 0.1% TBST then incubated with 0.2 m g/ml horseradish peroxidase-conjugated goat anti-rabbit IgG antibody (Santa Cruz Biotech) for 1 hr at room temperature. Signals were detected using SuperSignal West Pico Chemiluminescent Sub- strate (Thermo Scientific) and quantified using Bio-Rad2000 gel imaging system with QUANTITY ONE software (Biorad). Monoclonal mouse anti-beta actin antibody conjugated to HRP was used as a loading control at a concentration of 31 ng/ml.
In the present study, we demonstrated that Pla2g3 expression is increased in cerebral cortex but not in cerebellum by chronic oxidative stress with vitamin E deficiency. Pla2g3 is expressed both in neurons and astrocytes but oxidative stress-induced Pla2g3 expression is predomi- nantly in astrocytes in the cerebrum. It is particularly noteworthy that this increased Pla2g3 expression is absent in the astrogliosis induced by the ischemia or traumaticbraininjury to the cerebral cortex, indicating that not the acute oxidative stresses but the chronic oxidative stress is the essential factor for induction of Pla2g3 expression in vivo. Moreover, Pla2g3 expression is not associated with the formation of reactive astrocytes. This brain region-specific astrocytic induction of Pla2g3 may be due to the regional differences of vulnerability to the accumulation of oxidative stress during aging. In fact, cerebellum has been reported to be more resistant to oxidative stress than hippocampus and frontal cortex of human brain , which provides a rational explanation for the cerebral cortex specific induction of Pla2g3 we observed. Addition- ally, Pla2g5 and iPla2 did not increase significantly and Pla2g2e was not detectable by oxidative stress in vivo despite a marked simultaneous increase in TR-AST cells after hydrogen peroxide treatment (S1 Fig), suggesting that the regulation of PLA2s gene expression varies among the
In general, the ideal resuscitation fluid to treat the severely injured, hypotensive trauma patient should be safe, should expand blood volume, should improve oxygen delivery and possibly reduce oxygen demand, should not increase bleeding and should be easy to administer as well as be able to achieve these goals with a small volume. Research into the possibility of such a fluid was stimulated more than 30 years ago by encouraging results observed in an early study in hemorrhaging dogs (9), which were treated with a 4 ml/kg bolus of 7.5% hypertonic saline (HS). This bolus volume was equivalent to 10% of the shed blood volume, and the dogs experienced rapid improvements in blood pressure, cardiac output and, most importantly, survival. Later experiments performed in sheep (10) and swine (11) added 6% dextran-70 to sustain these improved hemodynamics, and this solution, HSD, attracted great interest from the military. Subsequent preclinical studies in different controlled hemorrhage models and animal species have shown similar benefits in outcomes with doses as low as 4 ml/kg (12). No potential resuscitation fluid has under- gone as extensive a pre-clinical evaluation and safety schedule as HSD.
Of 129 consecutive patients with TBIs who were eligible for extubation during the study period, 119 passed the SBT and were included in the study. Ten patients were excluded due to self-extubation in 3 cases, MV lasting <48 hours in 4 cases, and spinal cord injuryin 3 cases. Most of the volunteers were male (93.3%), the average age of the sample was 35.0±12.9 years old, and the MV lasted 8.1±3.6 days on average. With respect to treatment, 86 volunteers (72.3%) underwent surgery, and 33 volunteers (27.7%) received conservative treatment. Upon admission to the ICU, volume and pressure assist-control were the ventilation modes most frequently used in 71 (59.6%) and 46 (38.7%) participants, respectively. he demographic data, duration of MV, and clinical characterization of the 119 analyzed volunteers are described in table 1.
Our study presents several limitations. It is a descriptive, retrospective study with a relatively small number of patients, conducted in a single center, which reduces statistical power and adds selection bias. Our study population is heterogeneous in terms of their clinical characteristics, indications and opportunity for DC, and technique used, which limits the precision of our results. As mentioned previously, the inability to measure the size of the DC does not allow us to evaluate the impact of this factor on the clinical outcomes of our patients. Finally, clinical results on discharge from the ICU were measured, and no long-term follow-up, such as at 3 to 6 months, was performed.
In Volume 19 (1), CEFAC - Speech, Language, Hearing Sciences and Education Journal presents 14 articles from the Southeast, South and Northeast regions of Brazil, as well as 1 article from Chile, totaling 15 research publications with their regional characteristics, in different specialties of Speech Therapy.
certain types of braininjury since drugs may slow the rate of the neuronal death but not avoid it. Thus, the neuroprotective effect of DZ observed by Schwartz et al. (17) may not be long lasting; DZ may have merely de- layed hippocampal cell death (17). In an- other study, Schwartz et al. (37) found that the GABA reuptake inhibitor tiagabine was neuroprotective up to 4 days post-ischemia, but not after 21 days. Under the present experimental conditions, however, one limi- tation of this study was that the negative result with DZ alone hinders an interpreta- tion as to whether DZ does or does not facilitate the neuroprotective action of Mg 2+ .
1. Ferreira CB, Bassi E, Lucena L, Carreta H, Miranda LC, Tierno PF, et al. Measurement of intracranial pressure and short-term outcomes of patients withtraumaticbraininjury: a propensity-matched analysis. Rev Bras Ter Intensiva. 2015;27(4):315-21.
In the neuropsychological evaluation, we observed some dysfunctions that reinforce the comprehension of progression to SUD following both TBI and trauma. For example, in the Stroop Test, the impaired performance of F. in page-color and page word-color revealed an inhibitory control deficit. Inhibitory deficits are known as related to development of dysfunctional behavioral tendencies including impulsivity, aggression and a propensity for risky behaviors in individuals with TBI (Graham & Cardon, 2008; Teasdale & Engberg, 2001). These behaviors are commonly associated with an increase vulnerability mediating the transitions between SUD stages (Graham & Cardon, 2008; West, 2011). Other behavioral deficits, including difficulty in emotional regulation, depressive and anxiety behaviors, apathy and mood instability are also considered risk factors for drug addiction in TBI patients (Graham & Cardon, 2008; Taylor, Kreutzer, Demm, & Meade, 2003a) and were reported by the psychiatrist or observed in clinical profile of the patient described above. Given that these behavioral symptoms could be related or may be a consequence of cognitive flexibility impairments and inhibitory dysfunction, it is possible that progression from TBI to SUD is the result of interaction of a specific cognitive and behavior profile commonly observed in patients following severe TBI with PTSD.
Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be impor- tant for their clinical outcome. In the present investigation we studied tert -butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10- min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min), followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death inratsand gerbils submitted to a lethal (10 min) ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min) and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH) groups significantly contribute to the antioxidant capacity of plasma. There was a signifi- cant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along withbrain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the preconditioning phenomenon.
The loading plots (Figure 1b, Figure 3b) plot the relative contribution of each cytokine to the respective PC illustrated inin the scores plots. The loading plots allow us to explore the largest sources of variation within the dataset and identify clusters of cytokines that closely co-vary. The current literature on TBI and cytokines focuses on a relatively small group of mediators. The two cytokines most commonly implicated in a pro-inflammatory role are IL1b and TNF. These cytokines share intracellular transduction mechanisms  and have synergistic actions in cell culture models [27,28]_ENREF_35. They appear in the same quadrant in both PCA loading plots (top right figure 1b, bottom right figure 3b) suggesting concomitant production. Conversely, IL1ra, an endog- enous competitive antagonist to IL1b appears in the opposing quadrant of the loading plots (bottom right figure 1b, top right figure 3b). Interestingly, IL1a, another agonist at the IL-1 receptor appears immediately adjacent to IL1ra and therefore closely co- varies with IL1ra. This relationship has not previously been described in the literature. It is not possible to determine what the functional consequences of this relationship are simply based on the PCA model, however it may be that as IL1a is produced concurrently with IL1ra it may not act as effectively as an agonist at the IL1 receptor as IL1b. There is pre-clinical evidence demonstrating differential effects of IL1a and IL1b  as well as a more prominent role for IL1b in inducing neurodegeneration than for IL1a . This potentially adds to the considerable complexity in the regulation of the IL1 receptor pathway  and may result in differences in the potencies of IL1a and IL1b action in vivo. Furthermore, it clearly illustrates how biological mediators with opposing functions can closely co-vary. There is no way to definitively infer what a PC represents biologically, however, on the basis of the location of TNF, IL1b and IL1ra and the prior evidence for the role of these cytokines following TBI, we would suggest that PC2 represents some aspect of the pro-inflammatory consequences of IL1b/TNF action in contrast to the cytokines loading negatively on this axis.
At the moment of the first assessment, medical treatments in progress considered potentially futile included, nasogastric intubation (84.8%), urinary catheterization (66.7%), continuous cardiorespira- tory monitoring (50.0%), and hypocoagulation in therapeutic or prophylactic dose (36.3%) (Table 3). Six patients had tracheal intubation (5 orotracheal and 1 tracheotomy): the orotracheal tube was later removed from all five patients. The mean number of antibiotic cycles per patient prior to the request for collaboration with the IHTPCS was two, with one case of nine complete antibiotic cycles prior to the initial assessment.
nuevos estudios han abordado el asunto de si el monitoreo de la presión intracra- neana (PIC) es pertinente en el manejo del trauma encéfalo craneano grave y si se justiica el gasto en aras de conseguir un mejor resultado. El artículo: “Measurement of intracranial pressure and short-term outcome of patients withtraumaticbraininjury: a propensity-matched analysis” por Biselli-Ferreira et al., (2) publicado en este