Induction of oxidative stress and apoptosis in the injured brain: potential relevance to brain regeneration in zebrafish.

Recent findings suggest a significant role of the brain-derived neurotrophic factor (BDNF) as a mediator of brain regeneration following a stab injury in zebrafish. Since BDNF has been implicated in many physiological processes, we hypothesized that these processes are affected by brain injury in zebrafish. Hence, we examined the impact of stab injury on oxidative stress and apoptosis in the adult zebrafish brain. Stab wound injury (SWI) was induced in the right telencephalic hemisphere of the adult zebrafish brain and examined at different time points. The biochemical variables of oxidative stress insult and transcript levels of antioxidant genes were assessed to reflect upon the oxidative stress levels in the brain. Immunohistochemistry was performed to detect the levels of early apoptotic marker protein cleaved caspase-3, and the transcript levels of pro-apoptotic and anti-apoptotic genes were examined to determine the effect of SWI on apoptosis. The activity of antioxidant enzymes, the level of lipid peroxidation (LPO) and reduced glutathione (GSH) were significantly increased in the injured fish brain. SWI also enhanced the expression of cleaved caspase-3 protein and apoptosis-related gene transcripts. Our results indicate induction of oxidative stress and apoptosis in the telencephalon of adult zebrafish brain by SWI. These findings contribute to the overall understanding of the pathophysiology of traumatic brain injury and adult neurogenesis in the zebrafish model and raise new questions about the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum.

The central nervous system (CNS) of adult zebrafish is capable of recovering from injury, unlike the CNS of mammals such as humans or rodents. Previously, we established a stab wound injury model of the optic tectum (OT) in the adult zebrafish and showed that the radial glial cells (RG) proliferation and neuronal differentiation contributes to OT regeneration. In the present study, we analyzed the function of histone deacetylases (HDACs) as potential regulators of OT regeneration. The expression of both hdac1 and hdac3 was found to be significantly decreased in the injured OT. In order to analyze the roles of HDACs in RG proliferation and differentiation after injury, we performed pharmacological experiments using the HDAC inhibitor trichostatin A. We found that HDAC inhibition after stab wound injury suppressed RG proliferation but promoted neuronal differentiation. Moreover, HDAC inhibition suppressed the injury-induced decline in expression of Notch signaling target genes, her4.1 and her6 after OT injury. These results suggest that HDACs regulate regenerative neurogenesis through changes in Notch target gene expression by histone deacetylation. HDACs and histone acetylation are promising molecular targets for neuronal regeneration and further studies about the molecular mechanisms behind the regulation of regeneration by histone acetylation are necessary.

Stabbing angle alters peak force and work during sharp force trauma of porcine ribs.

Forensic anthropologists have traditionally relied on a qualitative scale (mild, moderate, severe) for describing the forces required to generate a bony injury; however, recently efforts have focused on providing more quantitative data. The current study considers the effects of blade angle on the peak force, average force, and work measured during an instrumented sharp force impact. Sixty-two porcine side ribs were stabbed with the long axis of the blade perpendicular to the convex surface and the blade edge in one of three orientations (0°, 45°, 90°). Peak force was highest when the cutting edge was perpendicular to the long axis of the rib (90°) and lowest when it was aligned (0°). Conversely, work was highest when the blade was at an oblique angle (45°) to the rib. These results confirm that the orientation of a sharp force event must be considered when estimating the mechanical loading required to generate an injury.

Penetrating injury to the cardiac box.

BACKGROUND: A penetrating injury to the "cardiac box" is thought to be predictive of an injury to the heart; however, there is very little evidence available to support this association. This study aims to evaluate the relationship between penetrating trauma to the cardiac box and a clinically significant injury. METHODS: All patients presenting to a Level I trauma center from January 2009 to June 2015 who sustained a penetrating injury isolated to the thorax were retrospectively identified. Patients were categorized according to the location of injury: within or outside the historical cardiac box. Patients with concurrent injuries both inside and outside the cardiac box were excluded. Clinical demographics, injuries, procedures, and outcomes were compared. RESULTS: During this 7-year period, 330 patients (92% male; median age, 28 years) sustained penetrating injuries isolated to the thorax: 138 (42%) within the cardiac box and 192 (58%) outside the cardiac box. By mechanism, 105 (76%) were stab wounds (SW) and 33 (24%) were gunshot wounds (GSW) inside the cardiac box, and 125 (65%) SW and 67 (35%) GSW outside the cardiac box. The overall rate of thoracotomy or sternotomy (35/138 [25.4%] vs. 15/192 [7.8%], p < 0.001) and the incidence of cardiac injury (18/138 [13%] vs. 5/192 [2.6%], p < 0.001) were significantly higher in patients with penetrating trauma within the cardiac box. This was, however, dependent on mechanism with SW demonstrating a higher incidence of cardiac injury (15/105 [14.3%] vs. 3/125 [2.4%], p = 0.001) and GSW showing no significant difference (3/33 [9.1%] vs. 2/67 [3%], p = 0.328]. There was no difference in overall mortality (9/138 [6.5%] vs. 6/192 [3.1%], p = 0.144). CONCLUSION: The role of the cardiac box in the clinical evaluation of a patient with a penetrating injury to the thorax has remained unclear. In this analysis, mechanism is important. Stab wounds to the cardiac box were associated with a higher risk of cardiac injury. However, for GSW, injury to the cardiac box was not associated with a higher incidence of injury. The diagnostic interaction between clinical examination and ultrasound, for the diagnosis of clinically significant cardiac injuries, warrants further investigation. LEVEL OF EVIDENCE: Prognostic study, Level IV, Therapeutic V.

Is there an association of hematopoietic stem cell and endothelial progenitor cell markers with maturation in forearm arterial repair?

OBJECTIVES: This study aims to assess the effects of the hematopoietic stem cells and endothelial progenitor cells in peripheral blood and monocyte cluster of differentiation (CD) 34, CD133 and CD309 expression levels on maturation at the repair site in patients who underwent forearm arterial repair. PATIENTS AND METHODS: This prospective study included 30 patients (23 males, 7 females; mean age 28.9±1.8 years; range, 18 to 49 years) with a well-defined cut at the wrist due to a stabbing injury but no comorbid condition who presented to the emergency department of our hospital between November 2014 and November 2017. Vascular patency was assessed by Doppler sonography in patients who underwent forearm arterial repair via micro-vascular techniques. The relationships between patency and hematopoietic stem and endothelial progenitor cell markers such as CD34, CD133 and CD309 were assessed by flow cytometry. RESULTS: The patients were divided into two groups according to presence of sufficient flow in the arteries repaired. The mean CD34 expression level was 72.09±3.00 in the group with maturation whereas it was 54.64±7.34 in the group without maturation, indicating a statistically significant difference (p<0.05). In addition, the likelihood of sufficient flow was increased by 1.075 per one unit increase in CD34 level. Resistive index values were significantly lower in the group with maturation and CD34 level was predictive for maturation of arterial repair. CONCLUSION: In the present study, the findings demonstrated that high CD34 expression level has favorable effects on maturation after arterial repair.

Penetrating intracranial trauma of two minors treated with endovascular technique with the use of temporary balloon occlusion for proximal arterial control.

We present two children treated with endovascular techniques to gain proximal arterial control of the internal carotid and vertebral artery prior to removal of penetrating objects from the skull base. Both siblings (8-month-old and 22-month-old boys) were injured by different sharp objects (knife and scissor) by a guardian. They were transported to the emergency room where vascular control, including coil embolisation and internal carotid balloon occlusion, was performed in the neuroendovascular suite for safe removal of penetrating objects. Both minors recovered and were discharged home without any focal neurological deficits. In two children with scissor and knife stab with intracranial penetration, endovascular technique allowed safe removal of objects and ensured proximal arterial control was maintained to control for possible extravasation of blood on removal from the skull base.

Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea.

Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1ß (IL-1ß), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor ß1 (TGFß1), interleukin-6 (IL-6), and tumor necrosis factor α at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGFß1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.

Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish.

Zebrafish have superior abilities to generate new neurons in the adult brain and to regenerate brain tissue after brain injury compared with mammals. There exist two types of neural stem cells (NSCs): neuroepithelial-like stem cells (NE) and radial glia (RG) in the optic tectum. We established an optic tectum stab injury model to analyze the function of NSCs in the regenerative condition and confirmed that the injury induced the proliferation of RG, but not NE and that the proliferated RG differentiated into new neurons after the injury. We then analyzed the involvement of Wnt signaling after the injury, using a Wnt reporter line in which canonical Wnt signaling activation induced GFP expression and confirmed that GFP expression was induced specifically in RG after the injury. We also analyzed the expression level of genes related to Wnt signaling, and confirmed that endogenous Wnt antagonist dkk1b expression was significantly decreased after the injury. We observed that Wnt signal inhibitor IWR1 treatment suppressed the proliferation and differentiation of RG after the injury, suggesting that up-regulation of Wnt signaling in RG after the stab injury was required for optic tectum regeneration. We also confirmed that Wnt activation by treatment with GSK3ß inhibitor BIO in uninjured zebrafish induced proliferation of RG in the optic tectum. This optic tectum stab injury model is useful for the study of the molecular mechanisms of brain regeneration and analysis of the RG functions in physiological and regenerative conditions.

Treatment of colorectal injuries in the civil war and the factors affecting mortality.

AIM: Colorectal injuries are one of the most common causes of mortality in war. Mainstay treatment of these injuries include primary repair or stoma creation. METHODS: Clinical data of the patients were evaluated retrospectively. Time from injury to hospital admission, method of treatment, the colorectal area affected, injury severity score ISS, hemodynamic instability, and mortality rate were determined. RESULTS: Of the 61 patients included in the study. Mean time from injury to hospital admission was 160±19 minutes. The injury was in the right colon in 24 patients 39.3%, in the left colon in 18 29.5%, and in the rectum in 19 31.2% patients. Median ISS value of 61 patients was 16, IQR 5. Mortality and complication rates were higher in patients with hemodynamic instability and stoma requirement was also higher in this group p<0.05. Total mortality occurred in 15 24.5% patients. Of these, 10 66.6% patients had hemodynamic instability. DISCUSSION: Hemodynamic instability is the most important factor affecting the mortality and the treatment method in wartime colorectal injuries. CONCLUSION: We believe that in victims of war with colorectal injuries, surgical intervention before the development of hemodynamic instability may reduce the rate of mortality and stoma requirement. KEY WORDS: Colorectal injury, Firearm injury, Hemodynamic instability, Stoma.

POSTERIOR PENETRATING INJURY OF THE NECK: A CASE REPORT.

- A 45-year-old male patient was admitted to the emergency unit due to posterior stab wound of the neck. The knife was directed diagonally from the left to the right side of the neck in the dorsoventral axis. The patient was fully conscious upon admission with pain and paresthesia along the upper right extremity. The patient underwent computed tomography (CT) and CT angiography scan of the neck, which revealed the knife blade piercing the left sided neck muscles and through the intervertebral ligaments of the C IV/C V in direction to the contralateral internal carotid artery, vertebral artery and the C5 nerve root. The patient underwent an urgent surgery according to the radiographs. Electromyography was performed during the early postoperative care and revealed an acute lesion of the right-sided C5 nerve root. Postoperative follow-up magnetic resonance imaging revealed intact brachial plexus bundles at the site of injury. Symptoms of reduced muscle strength and limited range of motion of the upper right extremity prevailed. Penetrating neck injuries represent a rare entity of all trauma injuries. Meticulous preoperative radiographs revealed close proximity of the knife blade tip to the right-sided vertebral artery and common carotid artery. Limited abduction at the right shoulder during postoperative period correlated to the C5 nerve root injury.

Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain.

Background: The development of Holmes tremor (HT) after a direct lesion of the midbrain has rarely been reported in the literature, although several etiologies have been linked with HT, such as stroke, brainstem tumors, multiple sclerosis, head trauma, or infections. Phenomenology Shown: A 31-year-old male, having been stabbed in the right eye, presented with a rest and action tremor in the left upper limb associated with left hemiparesis with corresponding post-contrast volumetric magnetic resonance imaging T1 with sagittal oblique reformation showing the knife trajectory reaching the right midbrain. Educational Value: Despite the rarity of the etiology of HT in the present case, clinicians working with persons with brain injuries should be aware of this type of situation.

Pseudoaneurysm of the Radial Artery on the Hand Secondary to Stabbing.

Pseudoaneurysm of the radial artery is extremely rare. It usually occurs secondary to trauma, interventional procedures, and infections. Symptoms occur due to mass effect by the pseudoaneurysm, digital ischemia, or nerve suppression. B-mode and color Doppler ultrasonography are the first choice in diagnosis. The pathognomonic ultrasound sign of pseudoaneurysm is the turbulent flow, which is called the "ying-yang" sign. Bandages, ultrasound probe compression, ultrasound-guided thrombin injection, covered stents, and surgical ligation can be used in treatment. In here, we present the case of a 28-year-old woman who developed a radial artery pseudoaneurysm after a stabbing injury in her hand and discuss the radiological and treatment options.

A stab wound to the axilla illustrating the importance of brachial plexus anatomy in an emergency context: a case report.

BACKGROUND: Although open injuries involving the brachial plexus are relatively uncommon, they can lead to permanent disability and even be life threatening if accompanied by vascular damage. We present a case report of a brachial plexus injury in which the urgency of the situation precluded the use of any ancillary diagnostic examinations and forced a rapid clinical assessment. CASE PRESENTATION: We report a case of a Portuguese man who had a stabbing injury at the base of his left axilla. On observation in our emergency room an acute venous type of bleeding was present at the wound site and, as a result of refractory hypotension after initial management with fluids administered intravenously, he was immediately carried to our operating room. During the course of transportation, we observed that he presented hypoesthesia of the medial aspect of his arm and forearm, as well as of the ulnar side of his hand and of the palmar aspect of the last three digits and of the dorsal aspect of the last two digits. Moreover, he was not able to actively flex the joints of his middle, ring, and small fingers or to adduct or abduct all fingers. Exclusively relying on our anatomical knowledge of the axillary region, the site of the stabbing wound, and the physical neurologic examination, we were able to unequivocally pinpoint the place of the injury between the anterior division of the lower trunk of his brachial plexus and the proximal portion of the following nerves: ulnar, medial cutaneous of his arm and forearm, and the medial aspect of his median nerve. Surgery revealed a longitudinal laceration of the posterior aspect of his axillary vein, and confirmed a complete section of his ulnar nerve, his medial brachial and antebrachial cutaneous nerves, and an incomplete section of the ulnar aspect of his median nerve. All structures were repaired microsurgically. Three years after the surgery he showed a good functional outcome. CONCLUSIONS: We believe that this case report illustrates the relevance of a sound anatomical knowledge of the brachial plexus in an emergency setting.

Impaired constitutive and regenerative neurogenesis in adult hyperglycemic zebrafish.

A growing body of evidence supports hyperglycemia as a putative contributor to several brain dysfunctions observed in diabetes patients, such as impaired memory capacity, neural plasticity, and neurogenic processes. Thanks to the persistence of radial glial cells acting as neural stem cells, the brain of the adult zebrafish constitutes a relevant model to investigate constitutive and injury-induced neurogenesis in adult vertebrates. However, there is limited understanding of the impact of hyperglycemia on brain dysfunction in the zebrafish model. This work aimed at exploring the impact of acute and chronic hyperglycemia on brain homeostasis and neurogenesis. Acute hyperglycemia was shown to promote gene expression of proinflammatory cytokines (il1ß, il6, il8, and tnfα) in the brain and chronic hyperglycemia to impair expression of genes involved in the establishment of the blood-brain barrier (claudin 5a, zona occludens 1a and b). Chronic hyperglycemia also decreased brain cell proliferation in most neurogenic niches throughout the forebrain and the midbrain. By using a stab wound telencephalic injury model, the impact of hyperglycemia on brain repair mechanisms was investigated. Whereas the initial step of parenchymal cell proliferation was not affected by acute hyperglycemia, later proliferation of neural progenitors was significantly decreased by chronic hyperglycemia in the injured brain of fish. Taken together, these data offer new evidence highlighting the evolutionary conserved adverse effects of hyperglycemia on neurogenesis and brain healing in zebrafish. In addition, our study reinforces the utility of zebrafish as a robust model for studying the effects of metabolic disorders on the central nervous system. J. Comp. Neurol. 525:442-458, 2017. © 2016 Wiley Periodicals, Inc.

Abdominal self-stabbing: A case report.

While abdominal stabbings are frequently associated with homicides, abdominal self-stabbing is uncommon and poses a challenge for the investigators. In cases of sharp force trauma, the presence of hesitation cuts over the neck and extremities help to distinguish self-inflicted injuries from homicides. Hesitation cuts are not associated with self-inflicted sharp force injuries to the abdomen, and thus are of limited use in distinguishing suicidal from homicidal abdominal stab wounds. In this study, we present a case of self-inflicted abdominal stabbing along with a detailed review of literature to help elucidate such cases.

Stabbing energy and force required for pocket-knives to pierce ribs.

PURPOSE: In addition to reconstructing the course of events, the medical examiner will often have to answer questions regarding the force necessary to inflict a certain injury in stabbing incidents. Several groups have examined the force needed to penetrate soft-tissue and clothing; however, no studies addressing the energy needed for penetrating ribs exist. Therefore, we decided to investigate this force on an animal model. METHOD: Ribs from healthy, 8 to 10-month-old pigs were used as a substitute for human ribs. These ribs were then stabbed either transversely or longitudinally with two different pocket-knife blades, namely a Swiss Army pocket knife and a sturdier pocket knife (Classic Schnitzmesser, Herbertz Solingen) dropped from a drop-tower at defined heights and therefore defined energies. RESULTS: Longitudinally orientated stabs showed complete piercing of the ribs at approximately 11 Joules (J) or with a stabbing force in excess of 906 Newton (N) for both blade types. Transversely orientated stabs, however, displayed complete piercing between 11 and 16 J, or in excess of 1198 N, with the sturdy pocket knife tending to require a little more energy than the Swiss army pocket knife. CONCLUSIONS: Young adult porcine ribs are completely pierced by pocket knife blades at energies between 11 and 16 J. Assuming the porcine ribs are comparable to those ribs of young adult humans, our results indicate that a complete penetration of the chest wall through the ribs by stabbing with a pocket knife is rather easily achieved.

Double-peaked Acetaminophen Concentration Secondary to Intestinal Trauma.

BackgroundReduced gastrointestinal motility can alter the toxicokinetics of acetaminophen poisoning. We report a case of altered acetaminophen toxicokinetics due to delayed gastrointestinal absorption, likely secondary to intestinal trauma/surgery.  Case ReportA 37-year-old woman ingested an unknown amount of acetaminophen and ethanol then stabbed herself in the abdomen. The initial acetaminophen was 1,285.9 µmol/L and the time of ingestion was not known. Intravenous acetylcysteine protocol was started. She developed an ileus post-surgery for the stab wounds. At 31 hours post-presentation, the acetaminophen returned undetectable, and the transaminases were normal. After the resolution of the ileus, repeated acetaminophen peaked at 363.3 µmol/L 52 hours post-admission. At 76 hours post-admission, the acetaminophen was undetectable, and transaminases and coagulation parameters were normal. ConclusionsReduction in gastrointestinal motility secondary to trauma and/or surgery must be considered when determining when to initiate or discontinue treatment as well as how long to monitor acetaminophen concentrations.