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Firesetting behaviors present multifaceted challenges that intersect the realms of mental health, law, and societal welfare. While distinct in nature, firesetting, arson, and pyromania collectively embody a spectrum of behaviors that cause harm with profound implications for mental health and legal system. Firesetting is a behavior, arson is a criminal offense, and pyromania is a classified psychiatric diagnosis. Nevertheless, the underlying motivations for these behaviors in the context of psychiatric symptomatoloty remain poorly understood. Arson alone exacts a staggering financial toll in the United States, emphasizing the urgent need to understand the reason behind these acts. Within legal contexts, mental health professionals frequently encounter individuals exhibiting firesetting behaviors while consulting on legal cases. The strong correlation between firesetting behavior and mental disorders shows a dire need for extensive and detailed collaboration between psychiatric experts, legal practitioners, and fire services. Here, we describe a series of firesetting cases and their ties to the mental health and legal systems underscoring the imperative for integrated, multifaceted approaches to address this pressing societal concern., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Segal et al.)

Background: There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity., Method: In this study, silk fibroin (SF) and tyramine-substituted gelatin (G-TA) were enzymatically crosslinked with human placental extracellular matrix (hpcECM) to produce silk-gelatin-ECM composite hydrogels (SGE) with tunable mechanical properties, preserved elasticity, and bioactive functions. The SGE composite hydrogels were characterized in terms of gelation kinetics, protein folding, and bioactivity. The cyto- and biocompatibility of the SGE composite was determined by in vitro cell culture and subcutaneous implantation in a rat model, respectively. The most cell-supportive SGE formulation was then used for 3-dimensional (3D) bioprinting that induced chemical crosslinking during extrusion., Conclusion: Addition of G-TA improved the mechanical properties of the SGE composite hydrogels and inhibited crystallization and subsequent stiffening of SF for up to one month. SGE hydrogels exhibit improved and tunable biomechanical properties and high bioactivity for encapsulated cells. In addition, its use as a bioink for 3D bioprinting with free reversible embedding of suspended hydrogels (FRESH) has been validated, opening the possibility to fabricate highly complex scaffolds for artificial soft tissue constructs with natural biomechanics in future., (© 2023. The Author(s).)

Psychotropic management of a first psychotic break is challenging for many psychiatrists. The literature shows that the use of cannabis is widespread in psychotic individuals. The literature also points to young males being most at risk for substance abuse. Studies also show that obstructive sleep apnea and the stress of the military lifestyle contribute to the development of psychosis. Here, we present a case study of a young non-combat veteran with a medical history of obstructive sleep apnea who presented to the Emergency Department of a Veteran's Affairs hospital with symptoms consistent with a first psychotic break. On routine admission laboratory work, his urine toxicology screen was positive for cannabis. Given the widespread use of cannabis in individuals with psychosis, we suggest that it plays an important role in the regulation of psychosis and behavior.

Federal law makes it a crime to threaten the President of the United States. The Secret Service conducts thousands of violence risk assessments each year. Literature suggests that 75% of individuals who make threats have been diagnosed with a mental illness (1). Studies show that prominent symptoms in presidential assassins include persecutory and grandiose delusions, hence falling into the category of psychotic disorders. We present a case of a patient diagnosed with Schizoaffective Disorder brought to CPEP (Comprehensive Psychiatric Emergency Program) by the Secret Service for repeatedly dialing 911 and making threats to the President. In the past year the patient had been hospitalized three times for similar behavior. Initial presentation included acute symptoms of psychosis and mania including persecutory delusions, command auditory hallucinations, grandiosity, and thought disorder. Clinicians were faced with unique challenges and consulted the forensic service to navigate the role of the Secret Service and develop a plan to prevent future episodes. The patient was discharged with a court order for treatment, long acting medication, as well as an outpatient appointment. The treatment plan has been effective and the Secret Service has ceased their investigation. We aim to explore issues in patient confidentiality, duty to both report and protect. We will also provide strategies and recommendations for such patients on the inpatient unit.

Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts - MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment. The implications of these findings are critically discussed.

Cell-therapy was proposed to be a promising tool in case of death or impairment of specific cell types. Correct identification of implanted cells became crucial when evaluating the success of transplantation therapy. Various methods of cell labeling have been employed in previously published studies. The use of intrinsic signaling of green fluorescent protein (GFP) has led to a well known controversy in the field of cardiovascular research. We encountered similar methodological pitfalls after transplantation of GFP-transfected embryonic stem cells into rat brains following traumatic brain injury (TBI). As the identification of implanted graft by intrinsic autofluorescence failed, anti-GFP labeling coupled to fluorescent and conventional antibodies was needed to visualize the implanted cells. Furthermore, different cell types with strong intrinsic autofluorescence were found at the sites of injury and transplantation, thus mimicking the implanted stem cells. GFP-positive stem cells were correctly localized, using advanced histological techniques. The activation of microglia/macrophages, accompanying the transplantation post TBI, was shown to be a significant source of artefacts, interfering with correct identification of implanted stem cells. Dependent on the strategy of stem cell tracking, the phagocytosis of implanted cells as observed in this study, might also impede the interpretation of results. Critical appraisal of previously published data as well as a review of different histological techniques provide tools for a more accurate identification of transplanted stem cells., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and/or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro. Rats were sacrificed at t = 45 minutes following lateral fluid-percussion injury and extracts of cerebral tissue were prepared from 4-6 healthy or injured rat brain hemispheres. Murine embryonic stem cells (CGR8) cultured in serum-free medium were then conditioned for a week with HBE or TBE. Omission of serum from the culture medium induced neural differentiation of CGR8 stem cells, as indicated by a significant time dependent down-regulation of oct-4 with a concomitant upregulation of nestin after 7 days. In parallel cell loss was observed that seemed to be largely due to apoptotic cell death. In TBE treated cells, on the other hand, a significant amplification of apoptotic cell death, enhancement of nestin and MAP2 expression and marked morphological changes such as axonal-like outgrowth was observed within 3 days of conditioning. Treatment of stem cells with HBE resulted in less pronounced neuronal differentiation processes. Axonal-like outgrowth was not observed. Our data suggest that during the early acute phase of traumatic injury the cerebral environment is disposed to detrimental as well as potent protective signals that seem to rapidly induce neurogenic processes., (Copyright © 2010 S. Karger AG, Basel.)

Although engraftment of undifferentiated pluripotent embryonic stem cells (ESCs) into the injured central nervous system (CNS) may lead to targeted cell replacement of lost/damaged cells, sustained proliferative activity combined with uncontrolled differentiation of implanted cells presents a risk of tumor formation. As tumorigenic potential is thought to be associated with pluripotency of embryonic stem cells, pre-differentiation may circumvent this problem. Recently, it has been demonstrated that tumorigenesis occurs despite pre-differentiation if the neural precursor cells are implanted into the brain of a homologous animal (e.g., mouse to mouse). However, xenotransplantation (e.g., mouse to rat) without pre-differentiation, lead to the development of healthy neuronal cells, in absence of tumor formation, suggesting that tumor-suppressive effects of host tissue on engrafted ESCs may play a role in transplant tumorigenesis. We critically investigated tumorigenesis and possible mechanisms of anticipated tumor-suppressive effect under conditions analogous to previously published studies. Xenotransplantation of D-3 murine ESCs into uninjured adult rat brains lacking any preliminary inflammatory potential was found to lead to tumor formation in 5 out of 8 of animals within 2 weeks postimplantation. Tumor-suppressive effects, reflected by Erdo et. al could possibly be ascribed to immunomodulatory activity of macrophages scavenging the tumorigenic fraction of the implanted cells. The importance of number of engrafted cells, implantation site and immunosuppressive effects are discussed as possible variables determining tumorigenic outcome after ESC transplantation., (2009 S. Karger AG, Basel.)

A variety of embryonic and adult stem cell lines require an initial co-culturing with feeder cells for non-differentiated growth, self renewal and maintenance of pluripotency. However for many downstream ES cell applications the feeder cells have to be considered contaminations that might interfere not just with the analysis of experimental data but also with clinical application and tissue engineering approaches. Here we introduce a novel technique that allows for the selection of pure feeder-freed stem cells, following stem cell proliferation on feeder cell layers. Complete and reproducible separation of feeder and embryonic stem cells was accomplished by adaptation of an automated cell selection system that resulted in the aspiration of distinct cell colonies or fraction of colonies according to predefined physical parameters. Analyzing neuronal differentiation we demonstrated feeder-freed stem cells to exhibit differentiation potentials comparable to embryonic stem cells differentiated under standard conditions. However, embryoid body growth as well as differentiation of stem cells into cardiomyocytes was significantly enhanced in feeder-freed cells, indicating a feeder cell dependent modulation of lineage differentiation during early embryoid body development. These findings underline the necessity to separate stem and feeder cells before the initiation of in vitro differentiation. The complete separation of stem and feeder cells by this new technology results in pure stem cell populations for translational approaches. Furthermore, a more detailed analysis of the effect of feeder cells on stem cell differentiation is now possible, that might facilitate the identification and development of new optimized human or genetically modified feeder cell lines.

Objective and Design: Cytokine-mediated immunoresponses are consequences of isolated traumatic brain injury (TBI) and muskuloskeletal trauma but little is known when both impacts occur simulanteously in combined neurotrauma (CNT), i. e. TBI + muskuloskeletal trauma (bone fracture)., Materials and Methods: A "two-hit"-experimental model of CNT (TBI + tibia fracture) was used to investigate circulating cytokine interleukin-1-beta, -6, -10 and sTNF-R1 concentrations following peripheral bone fracture only, TBI only and CNT. Blood samples were drawn at 30 min, 6 h, 24 h, 48 h, and 7 days following trauma and circulating cytokine concentrations were determined via immunoassay., Results: Circulating cytokines were increased after trauma (p <0.001 vs. controls), but peaked at different time points. sTNF R1 peaked first at 30 min, followed by IL-6 at 6 h after trauma. IL-10 levels were highest at 24 h, and those for IL-1beta at 48 h after trauma. Circulating IL-6 and IL-10 levels were highest in CNT at 8/10 time points studied (p <0.001)., Conclusion: Circulating cytokine IL-1-beta, -6, -10 and sTNF-R1 concentrations are increased after trauma (TBI, fracture and CNT) but peak at different time points. Pronounced IL-6 and IL-10 responses after CNT may contribute to the increased susceptibility for complications in CNT versus monotrauma.

In the present study, we compare the capacity of two different embryonic stem (ES) cell lines to secrete neurotrophins in response to cerebral tissue extract derived from healthy or injured rat brains. The intrinsic capacity of the embryonic cell lines BAC7 (feeder cell-dependent cultivation) to release brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) exceeded the release of these factors by CGR8 cells (feeder cell-free growth) by factors of 10 and 4, respectively. Nerve growth factor (NGF) was secreted only by BAC7 cells. Conditioning of cell lines with cerebral tissue extract derived from healthy or fluid percussion-injured rat brains resulted in a significant time-dependent increase in BDNF release in both cell lines. The increase in BDNF release by BAC7 cells was more pronounced when cells were incubated with brain extract derived from injured brain. However, differences in neurotrophin release associated with the origin of brain extract were at no time statistically significant. Neutrophin-3 and NGF release was inhibited when cell lines were exposed to cerebral tissue extract. The magnitude of the response to cerebral tissue extract was dependent on the intrinsic capacity of the cell lines to release neurotrophins. Our results clearly demonstrate significant variations in the intrinsic capability of different stem cell lines to produce neurotrophic factors. Furthermore, a significant modulation of neurotrophic factor release was observed following conditioning of cell lines with tissue extract derived from rat brains. A significant modulation of neurotrophin release dependent on the source of cerebral tissue extract used was not observed., ((c) 2007 Wiley-Liss, Inc.)

Pluripotent embryonic stem cells were shown to survive and differentiate into mature neuronal cells after implantation in experimental models of Parkinson disease and cerebral ischemia. Embryonic stem cell transplantation has also been proposed as a potential therapy for cerebral trauma, characteristic of massive loss of multiple cell types due to primary insult and secondary sequelae. Green fluorescent protein (GFP)-transfected murine embryonic stem cells were implanted into the ipsi or contralateral cortex of male Sprague-Dawley rats 72 h after fluid-percussion injury. Animals were sacrificed at day 5 or week 7 postimplantation. Brain sections were examined using conventional and fluorescent double-labelling immunohistochemistry. Five days after implantation, clusters of GFP-positive cells undergoing partial differentiation along neuronal pathway, were detected at the implantation site. However, after 7 weeks, only a few GFP-positive cells were found, indicating an extensive loss of stem cells during this time period. For the first time, we proved the observed cell loss to be mediated via phagocytosis of implanted cells by activated macrophages. Cerebral trauma, induced 3 days prior to implantation, has activated the inflammatory potential of otherwise immunologically privileged tissue. Subsequent cell implantation was accompanied by reactive astrogliosis, activation of microglia, as well as a massive invasion of macrophages into transplantation sites even if the grafts were placed into contralateral healthy hemispheres, remote from the traumatic lesion. Our results demonstrate a significant post-traumatic inflammatory response, which impairs survival and integration of implanted stem cells and has generally not been taken into account in designs of previous transplantation studies.

Transplantation of embryonic stem (ES) cells may provide cures for the damaged nervous system. Pre-differentiated ES or neuronal precursor cells have been investigated in various animal models of neurodegenerative diseases including traumatic brain injury (TBI). To our knowledge, no study has yet examined the effects of undifferentiated, murine ES cells on functional recovery and tumorigenity following implantation into injured rat brains. We evaluated the effect of transplantation of undifferentiated, murine embryonic cells on the recovery of motor function following lateral fluid percussion brain injury in Sprague-Dawley rats. At 3 days post-injury, animals received stereotactic injections of either embryonic stem cell suspension or injections of phosphate buffered saline without cells (control) into the injured cortex. Neurological motor function assessments were performed before injury, 72 h, 1, 3, and 6 weeks after transplantation using a Rotatrod and a Composite Neuroscore test. During this time period brain injured animals receiving ES cell transplantation showed a significant improvement in the Rotarod Test and in the Composite Neuroscore Test as compared to phosphate buffered saline (PBS)-treated animals. At 1 week post-transplantation, ES cells were detectable in 100% of transplanted animals. At 7 weeks following transplantation, EScells were detectable in only one animal. Two of 10 xenotransplanted animals revealed tumor formation over the observation period. These findings provide evidence for therapeutic potency of embryonic stem cell transplantation after TBI in rat, but also raise serious safety concerns about the use of such cells in human.

Aim: The aim of the survey was to elucidate the significance of postoperative pain therapy for the patient and its influence on the choice of hospital., Methods: This prospective, anonymous survey of consecutive patients in a general surgical clinic was performed by an independent study nurse., Results: A total of 161 patients were included; 90% of the surgical patients considered "good pain therapy" as a highly important factor, and three of four patients would admit themselves more likely to a clinic well known for "good pain therapy." If the patients could choose their hospital, factors such as "medical care by the physicians" are most important (rank 1; rank 1 most important, rank 10 most unimportant) followed by quality of "nursing care" (mean rank 2.6) and "good pain therapy" (mean rank 3.6). Older patients (> or = 60 years) preferred a hospital with known "good pain therapy" more often for surgical therapy than younger patients (< 60 years)., Conclusion: It can be concluded that postoperative pain relief is an important factor for the patients' selection of a clinic and is influenced by an age of > or = 60 years.

Objective: Postoperative care for ankle fractures is generally 1 of 2 regimens: 1) functional treatment combined with early weightbearing (EWB), or 2) immobilization in a cast/orthosis for 6 weeks without weightbearing (6WC). The objective of this study was 2-fold: 1) to follow a prospective group treated with EWB as to long-term subjective and objective outcomes, and 2) to compare a subset of this group with a matched group of historic controls treated with 6WC., Design: Prospective, clinical, cohort observation, and retrospective matched pair analysis., Setting: University hospital, level 1 trauma center., Patients: Forty-three patients (20 males; mean age, 49 +/- 14 years) with operated Weber B/C fractures underwent EWB. For comparison, 23 patients of this group were matched to a same number of historic controls with respect to age, gender, body mass index, and fracture type., Intervention: Open reduction and internal fixation (ORIF) using a 1/3-tubular-fibula-plate for the fibula, and malleolar screws for the medial malleolus fracture (in cases with a bimalleolar ankle fracture) followed by EWB or 6WC., Main Outcome Measurements: Olerud and Tegner scores at follow-up (at least 12 months after surgery), time to full weightbearing, return to work, pain intensity (numerical rating scale (NRS)), and hospital stay. Statistical comparisons were performed by using the Mann-Whitney U test or Fisher exact test (P < 0.05)., Results: Patients with EWB were full weightbearing at 7 +/- 3 weeks and returned to work at 8 +/- 5 weeks after surgery. At follow-up (mean, 20 +/- 11 months after surgery), all EWB patients showed good results in the Olerud score (90 +/- 13 points). Matched-pair analysis in 23 patients in each group revealed differences between EWB and 6WC groups for hospital stay (mean, 10.8 +/- 4.7 vs. 13.6 +/- 6 days; P = 0.12), time to full weightbearing (mean, 7.7 +/- 3.1 vs. 13.5 +/- 9.4 weeks; P = 0.01), and time until return to work (mean 9.2 +/- 5.5 vs. 10.8 +/- 7 weeks; P = 0.63). No differences concerning pain intensities were observed (EWB vs. 6WC: NRS = 1.9 vs. 1.7; P = 0.12). At follow-up, Olerud scores were generally considered good for both groups; however, mean values in EWB patients were slightly higher (87 +/- 14 vs. 79 +/- 19 points; P = 0.25). In both groups, the majority of patients reached their preinjury level of activity as demonstrated by Tegner scores., Conclusions: EWB patients tolerated earlier full weightbearing compared with 6WC patients, and there were no disadvantages with EWB compared with 6WC concerning hospital stay, pain intensities, time until return to work, and Olerud/Tegner Scores. Potential candidates for EWB are patients with a stable osteosynthesis of their fractured ankles as judged by the responsible surgeon, compliance, and high motivation.

Traumatic brain injury (TBI) is present in two-thirds of patients with multiple injuries and in one-third combined with injuries of the extremities. Studies on interactive effects between central and peripheral injuries are scarce due to the absence of clinically relevant models. To meet the demand for "more-hit" models, an experimental model of combined neurotrauma (CNT) incorporating a standardized TBI via lateral fluid percussion (LFP) together with a peripheral bone fracture, i.e., tibia fracture, is introduced. Sprague-Dawley rats were randomized to four experimental groups: controls (n = 10), animals with TBI (n = 30), animals with tibia fracture (n = 30), and animals with CNT (n = 30). Morphological aspects of brain and bone injury were analyzed via standard histopathological procedures and x-ray. Trauma-induced neuromotor dysfunction was assessed using a standardized neuroscore. For interactive effects between injuries, we studied the extent and temporal pattern of circulating interleukin 6 (IL-6) levels via immunoassay and callus formation at fracture sites by means of microradiography. LFP produced an ipsilateral lesion with cortical contusion, hemorrhage, mass shift, and neuronal cell loss (adjacent cortex and hippocampus CA-2/-3), along with contralateral neuromotor dysfunction. X-rays confirmed complete fractures in the middle of the bone shaft. The type of injury (P < 0.001) and time (P = 0.022) were significantly associated with increased IL-6 levels. CNT produced the highest IL-6 plasma levels with a maximum peak at 6 h after trauma (P < 0.001). Similarly, callus formation at fracture sites in CNT was significantly increased versus fracture only (P < 0,01). The CNT model mimics a variety of clinically relevant features known from human multiple injury, including TBI, and offers novel approaches for investigation of interactive mechanisms and therapeutic approaches.

Objective and Design: One of the factors defining cellular response might be the distribution and density of receptor subtypes on cell membranes. It was our aim to quantify and compare histamine H2 receptor expression in primary vascular cell types. We have therefore generated antibodies directed against the second extra-cellular loop of the H2 receptor., Methods: The specificity of polyclonal anti-H2 receptor antibodies designed for this purpose was examined by Western blot analysis and immunohistochemistry. H2 receptor expression was quantified by ELISA. Regulation of H2 receptor gene expression was analyzed by competitive RT-PCR., Results: Our results indicate that the polyclonal antibodies specifically interact with the histamine H2 receptor. Furthermore, utilizing these antibodies we were able to show significant differences in H2 receptor levels in human umbilical arterial and vein endothelial cells as well as smooth muscle cells., Conclusions: We conclude that the antibodies generated against the extra-cellular domain of the H2 receptor are specific and can be utilized to detect and quantify H2 receptor expression. Furthermore, the significant differences in H2 receptor expression in different vascular cell types might play a critical role in defining histamine induced cellular responses during physiological or pathophysiological processes.

Objective: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury., Methods: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were reanesthetized and randomized to receive stereotactic injection of NSCs or control cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 3 and 12 weeks after transplantation., Results: Brain-injured animals that received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers but not markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy)., Conclusion: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.

The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases.

Purpose: Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI., Methods: Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test., Results: Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration., Conclusion: These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI.

Objective: Besides interleukin (IL)-10, accumulating evidence from in vitro studies has indicated a strong antiinflammatory capacity for IL-13. A prospective clinical study was undertaken to assess the influence of additional brain injury on systemic IL-10 and IL-13 levels as markers for the antiinflammatory state in trauma patients., Material and Methods: The course of IL-10 and IL-13 plasma levels from 32 patients with an isolated severe head trauma (SHT), 50 patients with multiple injuries and additional SHT and 39 patients with multiple injuries without SHT was detected using ELISA-technique. Blood samples from 37 healthy blood donors were analysed for control., Results: IL-10 levels were significantly elevated in all 3 injury groups within 3 h after trauma. The lowest initial release was detected in patients with an isolated SHT (Injury severity score; ISS: 18.1 +/- 5.6). No difference could be demonstrated for the IL-10 levels from multiple injured patients with (ISS: 35.3 +/- 9.6) or without additional SHT (ISS: 25.5 +/- 11.7), though there were relevant differences in the ISS. In contrast, the IL-13 plasma levels were not elevated systemically after trauma., Conclusions: IL-10 but not IL-13 is a detectable antiinflammatory marker in trauma patients with or without brain injury and to a minor degree in patients with an isolated SHT.