Sensorimotor dysfunction in a mild mouse model of cortical contusion injury without significant neuronal loss is associated with increases in inflammatory proteins with innate but not adaptive immune functions.

Traumatic brain injury is a leading cause of mortality and morbidity in the United States. Acute trauma to the brain triggers chronic secondary injury mechanisms that contribute to long-term neurological impairment. We have developed a single, unilateral contusion injury model of sensorimotor dysfunction in adult mice. By targeting a topographically defined neurological circuit with a mild impact, we are able to track sustained behavioral deficits in sensorimotor function in the absence of tissue cavitation or neuronal loss in the contused cortex of these mice. Stereological histopathology and multiplex enzyme-linked immunosorbent assay proteomic screening confirm contusion resulted in chronic gliosis and the robust expression of innate immune cytokines and monocyte attractant chemokines IL-1ß, IL-5, IL-6, TNFα, CXCL1, CXCL2, CXCL10, CCL2, and CCL3 in the contused cortex. In contrast, the expression of neuroinflammatory proteins with adaptive immune functions was not significantly modulated by injury. Our data support widespread activation of innate but not adaptive immune responses, confirming an association between sensorimotor dysfunction with innate immune activation in the absence of tissue or neuronal loss in our mice.

Fibrinogen-cellular prion protein complex formation on astrocytes.

Traumatic brain injury (TBI) is one of the most common neurological disorders causing memory reduction, particularly short-term memory (STM). We showed that, during TBI-induced inflammation, increased blood content of fibrinogen (Fg) enhanced vascular protein transcytosis and deposition of extravasated Fg in vasculo-astrocyte interfaces. In addition, we found that deposition of cellular prion protein (PrPC) was also increased in the vasculo-astrocyte endfeet interface. However, association of Fg and PrPC was not confirmed. Presently, we aimed to define whether Fg can associate with PrPC on astrocytes and cause their activation. Cultured mouse brain astrocytes were treated with medium alone (control), Fg (2 mg/mL or 4 mg/mL), 4 mg/mL of Fg in the presence of a function-blocking anti-PrPC peptide or anti-mouse IgG, function-blocking anti-PrPC peptide, or anti-mouse IgG alone. After treatment, either cell lysates were collected and analyzed via Western blot or coimmunoprecipitation was performed, or astrocytes were fixed and their activation was assessed with immunohistochemistry. Results showed that Fg dose-dependently activated astrocytes, increased expressions of PrPC and tyrosine (tropomyosin) receptor kinase B (TrkB), and PrP gene. Blocking the function of PrPC reduced these effects. Coimmunoprecipitation demonstrated Fg and PrPC association. Since it is known that prion protein has a greater effect on memory reduction than amyloid beta, and that activation of TrkB is involved in neurodegeneration, our findings confirming the possible formation of Fg-PrPC and Fg-induced overexpression of TrkB on astrocytes suggest a possible triggering mechanism for STM reduction that was seen previously during mild-to-moderate TBI.NEW & NOTEWORTHY For the first time we showed that fibrinogen (Fg) can associate with cellular prion protein (PrPC) on the surface of cultured mouse brain astrocytes. At high levels, Fg causes upregulation of astrocyte PrPC and astrocyte activation accompanied with overexpression of tyrosine receptor kinase B (TrkB), which results in nitric oxide (NO) production and generation of reactive oxygen species (ROS). Fg/PrPC interaction can be a triggering mechanism for TrkB-NO-ROS axis activation and the resultant astrocyte-mediated neurodegeneration.

Mechanism of brain swelling in cases of brain evisceration due to catastrophic craniocerebral injury - an autopsy study.

Some previously reported cases of brain evisceration in catastrophic craniocerebral injuries showed the presence of brain swelling. The aim of this study was to observe the occurrence of focal or diffuse brain swelling in such cases in order to explain the underlying mechanism. An observational autopsy study included 23 adults, 18 males and 5 females, whose average age was 48 ± 22 years (range: 19-89 years) and who died as the result of catastrophic craniocerebral injury with brain evisceration. In all the examined cases, either focal (12 cases) or diffuse (11 cases) brain swelling was present. Grossly visible brain contusions (either cortical or deep) were rarely present - only in 6 out of 23 cases, while microscopic brain contusions were observed in 22 out of 23 cases, with 1 remaining case of microscopic subarachnoid bleeding. Blood aspiration in the lungs, as a vital reaction, was noted in 20 out of 23 cases. Microscopic examination showed absence of edema in 20 cases and mild edema in only 3 cases, while microscopic signs of moderate or severe edema were absent. Brain swelling in cases of brain evisceration likely represents a biomechanical reaction (i.e. decompression) due to a sudden decrease in intracranial pressure. The rapidity of death, together with marked absence of microscopic signs of edema, suggests that this is not a form of biological response to injury, but rather a pure physical phenomenon, strictly in a living person. In such cases, the occurrence of brain swelling and parenchymal microbleeding should be considered vital reactions.

Application of neuro-endoscopic target aspiration of the necrotic core for cerebral contusion with delayed progression: technical note.

BACKGROUND: The optimal management strategy for cerebral contusion remains controversial, especially when standard craniotomy could not be used. We performed neuro-endoscopic target lesionectomy for the delayed progression of cerebral contusion in order to aspirate the necrotic core, which is the primal source of contusional edema. METHODS: The present study included 10 consecutive patients (2 women and 8 men, with a mean age of 67 years old) with traumatic brain injury presenting with delayed deterioration of cerebral contusion where standard craniotomy could not be used. Neuro-endoscopic aspiration of the necrotic core was prospectively performed for all patients. We assessed the computed tomography findings after surgery to evaluate the efficacy of this procedure. RESULTS: Endoscopic surgery was performed promptly after neurological deterioration, with a mean interval between trauma and surgery of 7 days, ranging from 2 to 16 days. During the operation, the centers of contusions comprised serous liquid components in all 10 patients and were easily aspirated by endoscopy. Contusional edemas were markedly decreased in all within 3 days after surgery. CONCLUSIONS: Progression of contusional edema can be caused by the accumulation of water into the necrotic core due to the rapid increase in osmolality. In light of the highly liquefied demarcated characteristics of the necrotic core, neuro-endoscopic aspiration could be an optional treatment strategy for cerebral contusion with delayed progression in a minimally invasive manner.

Neurostereologic Lesion Volumes and Spreading Depolarizations in Severe Traumatic Brain Injury Patients: A Pilot Study.

BACKGROUND: Spreading depolarizations (SDs) occur in 50-60% of patients after surgical treatment of severe traumatic brain injury (TBI) and are independently associated with unfavorable outcomes. Here we performed a pilot study to examine the relationship between SDs and various types of intracranial lesions, progression of parenchymal damage, and outcomes. METHODS: In a multicenter study, fifty patients (76% male; median age 40) were monitored for SD by continuous electrocorticography (ECoG; median duration 79 h) following surgical treatment of severe TBI. Volumes of hemorrhage and parenchymal damage were estimated using unbiased stereologic assessment of preoperative, postoperative, and post-ECoG serial computed tomography (CT) studies. Neurologic outcomes were assessed at 6 months by the Glasgow Outcome Scale-Extended. RESULTS: Preoperative volumes of subdural and subarachnoid hemorrhage, but not parenchymal damage, were significantly associated with the occurrence of SDs (P's < 0.05). Parenchymal damage increased significantly (median 34 ml [Interquartile range (IQR) - 2, 74]) over 7 (5, 8) days from preoperative to post-ECoG CT studies. Patients with and without SDs did not differ in extent of parenchymal damage increase [47 ml (3, 101) vs. 30 ml (- 2, 50), P = 0.27], but those exhibiting the isoelectric subtype of SDs had greater initial parenchymal damage and greater increases than other patients (P's < 0.05). Patients with temporal clusters of SDs (≥ 3 in 2 h; n = 10 patients), which included those with isoelectric SDs, had worse outcomes than those without clusters (P = 0.03), and parenchymal damage expansion also correlated with worse outcomes (P = 0.01). In multivariate regression with imputation, both clusters and lesion expansion were significant outcome predictors. CONCLUSIONS: These results suggest that subarachnoid and subdural blood are important primary injury factors in provoking SDs and that clustered SDs and parenchymal lesion expansion contribute independently to worse patient outcomes. These results warrant future prospective studies using detailed quantification of TBI lesion types to better understand the relationship between anatomic and physiologic measures of secondary injury.

Axe injury pattern in homicide.

Chop or slash wounds are produced by sharp-edged tools such as an axe, or a machete. This paper presents a case of a violent death of a 57 year-old-man. Autopsy revealed deformation of the right side of the head. A total of 23 slash, stab and cut wounds as well as contused lacerations were identified on the scalp as well as the face and the neck. In addition, superficial abrasions and bruises were identified on the skin. The immediate cause of death was due to extensive brain contusion following fragmentation of the neurocranium. The injuries resulting in the death of the victim were sustained during an assault on the head with an axe, which was used both as a slashing tool and a blunt instrument.

Fatal Road Traffic Vehicle Collisions With Pedestrian Victims: Forensic Postmortem Computed Tomography and Autopsy Correlation.

Fatal car-to-pedestrian collisions regularly appear in the forensic pathologist's routine, particularly in places of extended urbanization. Postmortem computed tomography has gained an exceptional role to supplement autopsy worldwide, giving information that is supplementary or complimentary to conventional autopsy. In this retrospective study, a total number of 320 findings in a series of 21 pedestrians fatally hit by cars and trucks of both postmortem computed tomography and autopsy were correlated. According to our results, it is best to combine both methods to give well-founded answers to questions pertaining to both collision reconstruction and cause of death.

[The Role of CBS in Injury Time Estimation after Brain Contusion].

OBJECTIVES: To observe the changes of cystathionine ß-synthase （CBS） expression in the cerebral cortex after brain contusion at different times. METHODS: An experimental model of traumatic brain injury （TBI） in mice was established by an improved weight-drop device. Then Western blotting and immunohistochemical examination were used to detect the CBS expression in cerebral cortex around injury at different time points （1 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d）. RESULTS: The results of Western blotting revealed that the expression level of CBS was down-regulated and reached its lowest level at the 3rd days after injury, and then restored to normal level after 7 days. The results of immunohistochemistry showed that CBS was present in the normal brain cortex. CBS expression gradually decreased at the 3rd days after injury, and then restored to normal level after 7 days. CONCLUSIONS: CBS has the potential to be a reference index for time estimation after brain contusion in forensic practice.

[APPLICATION OF ALLOGENIC TISSUE OF THE FETAL BRAIN CORTEX AND THE OLFACTORY BULB TISSUE FOR TREATMENT OF THE BRAIN CONTUSION IN RATS].

Impact of the allogenic tissue transplantation of the fetal cerebral large hemispheres and the оlfactory bulb tissue (OBT) on the healing processes after the brain contusion was studied in experiment. The investigation was performed on mongrel male rats: in laboratory animals of the first group in the first day after open penetrating local cerebral trauma (OPLCT) the allogenic fetal nervous tissue fragment was transplanted into the formatted tissue defect; for the second group ­ in the first day after cerebral trauma the allogenic OBT fragment was transplanted into the formatted tissue defect; and for the third group (control) - the OPLCT was done without further transplantation of tissues. The impact of the allogenic fetal nervous tissue transplantation was demonstrated by more active participation of glial cells during the healing process course, and the OBT transplantation was followed by activation of neoangiogenesis processes , mainly in the injured brain. The experimental simulation choosed permits to study the possibilities of application of neurogenic tissues in the brain contusion treatment, and to determine the therapy tactics.

Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury.

The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than injuries to the adult brain. Understanding this developmental sensitivity is critical because children under 4 years of age of sustain TBI more frequently than any other age group. One of the first events after TBI is the infiltration and degranulation of mast cells (MCs) in the brain, releasing a range of immunomodulatory substances; inhibition of these cells is neuroprotective in other types of neonatal brain injury. This study investigates for the first time the role of MCs in mediating injury in a P7 mouse model of pediatric contusion-induced TBI. We show that various neural cell types express histamine receptors and that histamine exacerbates excitotoxic cell death in primary cultured neurons. Cromoglycate, an inhibitor of MC degranulation, altered the inflammatory phenotype of microglia activated by TBI, reversing several changes but accentuating others, when administered before TBI. However, without regard to the time of cromoglycate administration, inhibiting MC degranulation did not affect cell loss, as evaluated by ventricular dilatation or cleaved caspase-3 labeling, or the density of activated microglia, neurons, or myelin. In double-heterozygous cKit mutant mice lacking MCs, this overall lack of effect was confirmed. These results suggest that the role of MCs in this model of pediatric TBI is restricted to subtle effects and that they are unlikely to be viable neurotherapeutic targets. © 2016 Wiley Periodicals, Inc.

A positive correlation exists between neurotrauma and TGF-ß1-containing microglia in rats.

BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD™ (MLC601) and astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF-ß1. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (120 in number) were used to investigate the contribution of TGF-ß1-containing microglia in the MLC601-mediated or the AST-mediated neuroprotection in the brain trauma condition using lateral fluid percussion injury. RESULTS: Pearson correlation analysis revealed that there was a positive correlation between brain injury (evidenced by both brain contused volume and neurological severity score) and the cortical numbers of TGF-ß1-containing microglia for the rats (n = 12) 4 days post-TBI. MLC601 or AST significantly (P < 0·05) attenuated TBI-induced brain contused volume (119 ± 14 mm3 or 108 ± 11 mm3 vs. 160 ± 21 mm3 ), neurological severity score (7·8 ± 0·3 or 8·1 ± 0·4 vs. 10·2 ± 0·5) and numbers of TGF-ß1-containing microglia (6% ± 2% or 11% ± 3% vs. 79% ± 7%) for the rats 4 days post-TBI. CONCLUSIONS: There was a positive correlation between TBI and cortical numbers of TGF-ß1-containing microglia which could be significantly attenuated by astragaloside or NeuroAiD™ (MLC601) in rats.

Nrf2 knockout: The effect on neurological dysfunction and the activation of glial cells of mice after brain injury.

To investigate the protective role and possible mechanisms of Nrf2 gene in cerebral trauma in mice. The types Nrf2(-/-) and Nrf2(+/+) mice were confirmed by PCR, and the model of closed head injury was established. The severity of injury and the effect of the injury on neurological status were assessed by Neurological Severity Score (NSS) and fatality rate, and the activated conditions of microglia and astrocyte around the injured area were observed by immunohistochemical method. Compared with Nrf2(+/+) mice, the nerve dysfunction of the Nrf2(-/-) mice was obviously more severe (P<0.01). On the first day after injury, the activation of microglia around the injured area increased significantly in Nrf2 (-/-) mice, the difference was more significant on the third day, and there was still statistical difference until the 7th day (P<0.05). Moreover, On the days 1, 3, 7 after injury, the activation of astrocyte around the injured area also increased in Nrf2(-/-) mice, however, there was statistical difference only on the 3rd day (P<0.05). Nrf2 gene knockout can aggravate the nerve dysfunction after cerebral trauma, and this effect is achieved, at least partly, possibly via the effect of Nrf2 on glial activation.

[CRANIO­CEREBRAL TRAUMA WITH ESTIMATED SEVERITY OF 13­15 POINTS IN ACCORDANCE TO GLASGOW SCALE ­ A LIGHT TRAUMA].

Retrospective analysis of cranio­cerebral trauma (CCT) in 141 injured persons, ageing (38.3 ± 14.3) yrs at average, severity of which in accordance to Glasgow scale was estimated in 13 ­ 15 points, was performed. The injured persons were managed in accordance to actual recommendations of Ministry of Health of Ukraine. In accordance to CT data, the brain commotion was noted in 40 patients, the brain contusion type І ­ in 25, the brain contusion type ІІ with the skull fornix fracture ­ in 30, with linear fracture of the skull bones and traumatic hematomas into the brain­tunics ­ in 30, with fracture of the temporal bone pyramid ­ in 16. In indices 14 points and less (in accordance to Glasgow scale) in terms up to 24 h after CCT and absence of alcohol intoxication in 76.9% injured persons in accordance to CT data the intracranial traumatic affections were revealed. In indices of 15 points in 21% of injured persons false­negative results were determined, witnessing disparity of CCT signs with a CT data.

The p53 inactivators pifithrin-µ and pifithrin-α mitigate TBI-induced neuronal damage through regulation of oxidative stress, neuroinflammation, autophagy and mitophagy.

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. We investigated whether inhibition of p53 using pifithrin (PFT)-α or PFT-µ provides neuroprotective effects via p53 transcriptional dependent or -independent mechanisms, respectively. Sprague Dawley rats were subjected to controlled cortical impact TBI followed by the administration of PFTα or PFT-µ (2 mg/kg, i.v.) at 5 h after TBI. Brain contusion volume, as well as sensory and motor functions were evaluated at 24 h after TBI. TBI-induced impairments were mitigated by both PFT-α and PFT-µ. Fluoro-Jade C staining was used to label degenerating neurons within the TBI-induced cortical contusion region that, together with Annexin V positive neurons, were reduced by PFT-µ. Double immunofluorescence staining similarly demonstrated that PFT-µ significantly increased HO-1 positive neurons and mRNA expression in the cortical contusion region as well as decreased numbers of 4-hydroxynonenal (4HNE)-positive cells. Levels of mRNA encoding for p53, autophagy, mitophagy, anti-oxidant, anti-inflammatory related genes and proteins were measured by RT-qPCR and immunohistochemical staining, respectively. PFT-α, but not PFT-µ, significantly lowered p53 mRNA expression. Both PFT-α and PFT-µ lowered TBI-induced pro-inflammatory cytokines (IL-1ß and IL-6) mRNA levels as well as TBI-induced autophagic marker localization (LC3 and p62). Finally, treatment with PFT-µ mitigated TBI-induced declines in mRNA levels of PINK-1 and SOD2. Our data suggest that both PFT-µ and PFT-α provide neuroprotective actions through regulation of oxidative stress, neuroinflammation, autophagy, and mitophagy mechanisms, and that PFT-µ, in particular, holds promise as a TBI treatment strategy.

Intraparenchymal Application of Mature B Lymphocytes Improves Structural and Functional Outcome after Contusion Traumatic Brain Injury.

Cerebral contusion causes neurological dysfunction mediated in part by inflammatory responses to injury. B lymphocytes are dynamic regulators of the immune system that have not been systematically studied in traumatic brain injury (TBI). We showed previously that topically applied mature B cells have immunomodulatory properties and strongly promote tissue regeneration, including cutaneous nerve growth, in acute and chronic skin wounds. Using a mouse controlled cortical impact (CCI) model, we assessed a possible beneficial role of exogenously applied B cells on histopathological and functional outcome after TBI. Mice were injected intraparenchymally at the lesion site with 2 × 106 mature naïve syngeneic splenic B cells, then subjected to CCI. Control CCI mice received equal numbers of T cells or saline, and sham-injured mice (craniotomy only) were given B cells or saline. Sham-injured groups performed similarly in motor and learning tests. Injured mice administered B cells showed significantly improved post-injury rotarod, Y maze, and Morris water maze (MWM) performance compared with saline- or T-cell-treated CCI groups. Moreover, lesion volume in mice treated with B cells was significantly reduced by 40% at 35 days post-TBI compared with saline and T cell controls, and astrogliosis and microglial activation were decreased. In vivo tracking of exogenous B cells showed that they have a limited life span of approximately 14 days in situ and do not appear to proliferate. The data suggest proof of principle that local administration of B lymphocytes may represent a therapeutic option for treatment of cerebral contusion, especially when clinical management involves procedures that allow access to the injury site.

Interleukin-1 Receptor 1 Deletion in Focal and Diffuse Experimental Traumatic Brain Injury in Mice.

Important differences in the biology of focal and diffuse traumatic brain injury (TBI) subtypes may result in unique pathophysiological responses to shared molecular mechanisms. Interleukin-1 (IL-1) signaling has been tested as a potential therapeutic target in preclinical models of cerebral contusion and diffuse TBI, and in a phase II clinical trial, but no published studies have examined IL-1 signaling in an impact/acceleration closed head injury (CHI) model. We hypothesized that genetic deletion of IL-1 receptor-1 (IL-1R1 KO) would be beneficial in focal (contusion) and CHI in mice. Wild type and IL-1R1 KO mice were subjected to controlled cortical impact (CCI), or to CHI. CCI produced brain leukocyte infiltration, HMGB1 translocation and release, edema, cell death, and cognitive deficits. CHI induced peak rotational acceleration of 9.7 × 105 ± 8.1 × 104 rad/s2, delayed time to righting reflex, and robust Morris water maze deficits without deficits in tests of anxiety, locomotion, sensorimotor function, or depression. CHI produced no discernable acute plasmalemma damage or cell death, blood-brain barrier permeability to IgG, or brain edema and only a modest increase in brain leukocyte infiltration at 72 h. In both models, mature (17 kDa) interleukin-1 beta (IL-1ß) was induced by 24 h in CD31+ endothelial cells isolated from injured brain but was not induced in CD11b+ cells in either model. High mobility group box protein-1 was released from injured brain cells in CCI but not CHI. Surprisingly, cognitive outcome in mice with global deletion of IL-1R1 was improved in CHI, but worse after CCI without affecting lesion size, edema, or infiltration of CD11b+/CD45+ leukocytes in CCI. IL-1R1 may induce unique biological responses, beneficial or detrimental to cognitive outcome, after TBI depending on the pathoanatomical subtype. Brain endothelium is a hitherto unrecognized source of mature IL-1ß in both models.

Cavitation-induced traumatic cerebral contusion and intracerebral hemorrhage in the rat brain by using an off-the-shelf clinical shockwave device.

Traumatic cerebral contusion and intracerebral hemorrhages (ICH) commonly result from traumatic brain injury and are associated with high morbidity and mortality rates. Current animal models require craniotomy and provide less control over injury severity. This study proposes a highly reproducible and controllable traumatic contusion and ICH model using non-invasive extracorporeal shockwaves (ESWs). Rat heads were exposed to ESWs generated by an off-the-shelf clinical device plus intravenous injection of microbubbles to enhance the cavitation effect for non-invasive induction of injury. Results indicate that injury severity can be effectively adjusted by using different ESW parameters. Moreover, the location or depth of injury can be purposefully determined by changing the focus of the concave ESW probe. Traumatic contusion and ICH were confirmed by H&E staining. Interestingly, the numbers of TUNEL-positive cells (apoptotic cell death) peaked one day after ESW exposure, while Iba1-positive cells (reactive microglia) and GFAP-positive cells (astrogliosis) respectively peaked seven and fourteen days after exposure. Cytokine assay showed significantly increased expressions of IL-1ß, IL-6, and TNF-α. The extent of brain edema was characterized with magnetic resonance imaging. Conclusively, the proposed non-invasive and highly reproducible preclinical model effectively simulates the mechanism of closed head injury and provides focused traumatic contusion and ICH.

(-)-Phenserine Ameliorates Contusion Volume, Neuroinflammation, and Behavioral Impairments Induced by Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), a major cause of mortality and morbidity, affects 10 million people worldwide, with limited treatment options. We have previously shown that (-)-phenserine (Phen), an acetylcholinesterase inhibitor originally designed and tested in clinical phase III trials for Alzheimer's disease, can reduce neurodegeneration after TBI and reduce cognitive impairments induced by mild TBI. In this study, we used a mouse model of moderate to severe TBI by controlled cortical impact to assess the effects of Phen on post-trauma histochemical and behavioral changes. Animals were treated with Phen (2.5 mg/kg, IP, BID) for 5 days started on the day of injury and the effects were evaluated by behavioral and histological examinations at 1 and 2 weeks after injury. Phen significantly attenuated TBI-induced contusion volume, enlargement of the lateral ventricle, and behavioral impairments in motor asymmetry, sensorimotor functions, motor coordination, and balance functions. The morphology of microglia was shifted to an active from a resting form after TBI, and Phen dramatically reduced the ratio of activated to resting microglia, suggesting that Phen also mitigates neuroinflammation after TBI. While Phen has potent anti-acetylcholinesterase activity, its (+) isomer Posiphen shares many neuroprotective properties but is almost completely devoid of anti-acetylcholinesterase activity. We evaluated Posiphen at a similar dose to Phen and found similar mitigation in lateral ventricular size increase, motor asymmetry, motor coordination, and balance function, suggesting the improvement of these histological and behavioral tests by Phen treatment occur via pathways other than anti-acetylcholinesterase inhibition. However, the reduction of lesion size and improvement of sensorimotor function by Posiphen were much smaller than with equivalent doses of Phen. Taken together, these results show that post-injury treatment with Phen over 5 days significantly ameliorates severity of TBI. These data suggest a potential development of this compound for clinical use in TBI therapy.

Relationships between executive function, working memory, and decision-making on the Iowa Gambling Task: Evidence from ventromedial patients, dorsolateral patients, and normal subjects.

The results of previous studies are inconsistent in regard to the relationship between the Iowa Gambling Task (IGT), working-memory (WM), and executive tasks, and whether these cognitive processes could be considered as mechanisms underlying a decision-making deficit. Moreover, the relationship between the IGT and executive measures is examined based on a limited number of executive tasks, within different populations showing diffuse damage. In addition, there are fewer studies carried out within control participants, with those studies also being inconclusive. It is also suggested that the association of the IGT performance with executive tasks depends on whether the IGT was running under ambiguity or under risk. In this work, all of these issues are studied. Results showed that both patients with ventromedial (VMPFC, N = 10) and dorsolateral (DLPFC, N = 10) prefrontal cortex lesions are significantly impaired on almost all executive tasks, WM tasks, and the IGT. Furthermore, when the IGT is run under risk, there are significant correlations between executive measures and the IGT for the DLPFC patients and the control participants (N = 34) but not the VMPFC patients. No correlation was found between WM tasks and the IGT for both frontal subgroups and control participants. These findings suggested that the mechanisms underlying the IGT deficit differ according to the lesion locations.

Dual-Energy CT in Hemorrhagic Progression of Cerebral Contusion: Overestimation of Hematoma Volumes on Standard 120-kV Images and Rectification with Virtual High-Energy Monochromatic Images after Contrast-Enhanced Whole-Body Imaging.

BACKGROUND AND PURPOSE: In patients with hemorrhagic contusions, hematoma volumes are overestimated on follow-up standard 120-kV images obtained after contrast-enhanced whole-body CT. We aimed to retrospectively determine hemorrhagic progression of contusion rates on 120-kV and 190-keV images derived from dual-energy CT and the magnitude of hematoma volume overestimation. MATERIALS AND METHODS: We retrospectively analyzed admission and follow-up CT studies in 40 patients with hemorrhagic contusions. After annotating the contusions, we measured volumes from admission and follow-up 120-kV and 190-keV images using semiautomated 3D segmentation. Bland-Altman analysis was used for hematoma volume comparison. RESULTS: On 120-kV images, hemorrhagic progression of contusions was detected in 24 of the 40 patients, while only 17 patients had hemorrhagic progression of contusions on 190-keV images (P = .008). Hematoma volumes were systematically overestimated on follow-up 120-kV images (9.68 versus 8 mm3; mean difference, 1.68 mm3; standard error, 0.37; P < .001) compared with 190-keV images. There was no significant difference in volumes between admission 120-kV and 190-keV images. Mean and median percentages of overestimation were 29% (95% CI, 18-39) and 22% (quartile 3 - quartile 1 = 36.8), respectively. CONCLUSIONS: The 120-kV images, which are comparable with single-energy CT images, significantly overestimated the hematoma volumes, hence the rate of hemorrhagic progression of contusions, after contrast-enhanced whole-body CT. Hence, follow-up of hemorrhagic contusions should be performed on dual-energy CT, and 190-keV images should be used for the assessment of hematoma volumes.