Simulating traumatic brain injury in vitro:developing high throughput models to test biomaterial based therapies

Traumatic brain injuries are serious clinical incidents associated with some of the poorest outcomes in neurological practice.Coupled with the limited regenerative capacity of the brain,this has significant implications for patients,carers,and healthcare systems,and the requirement for life-long care in some cases.Clinical treatment currently focuses on limiting the initial neural damage with longterm care/support from multidisciplinary teams.Therapies targeting neuroprotection and neural regeneration are not currently available but are the focus of intensive research.Biomaterial-based interventions are gaining popularity for a range of applications including biomolecule and drug delive ry,and to function as cellular scaffolds.Experimental investigations into the development of such novel therapeutics for traumatic brain injury will be critically underpinned by the availability of appropriate high thro ughput,facile,ethically viable,and pathomimetic biological model systems.This represents a significant challenge for researchers given the pathological complexity of traumatic brain injury.Specifically,there is a concerted post-injury response mounted by multiple neural cell types which includes microglial activation and astroglial scarring with the expression of a range of growth inhibito ry molecules and cytokines in the lesion environment.Here,we review common models used for the study of traumatic brain injury(ranging from live animal models to in vitro systems),focusing on penetrating traumatic brain injury models.We discuss their relative advantages and drawbacks for the developmental testing of biomaterial-based therapies.

Novel rodent models of penetrating traumatic brain injury

A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of injury is particularly common in areas plagued by armed conflicts or gun-related violence.

Intentional Penetrating Craniocerebral Injury Caused by a Nail: Clinical Presentation and Management of Three Cases

The authors report on their experience in the medical and surgical management of three cases of penetrating craniocerebral injuries caused by a nail. In all three cases, it was an aggression. Two of the three patients were male. The cranial locations affected were respectively left parietal, right temporal and right frontal. The Glasgow coma score (GCS) was between 9 and 13. None of the patients had a motor deficit. A plain skull radiographs was performed for each patient. All patients underwent surgery and all received antibiotic therapy and tetanus vaccination. In two cases, post-operative outcome was simple. Recovery was complete without sequelae. The patient with a GCS of 9 died the day after surgery.

Transorbital nonmissile penetrating brain injury: Report of two cases

BACKGROUND Penetrating brain injury(PBI) is an uncommon emergency in neurosurgery, and transorbital PBI is a rare type of PBI. Reasonable surgical planning and careful postoperative management can improve the prognosis of patients CASE SUMMARY The first case is a 68-year-old male patient who was admitted to the hospital because a branch punctured his brain through the orbit for approximately 9 h after he unexpectedly fell while walking. After admission, the patient underwent emergency surgical treatment and postoperative anti-infection treatment. The patient was able to follow instructions at a 4-mo follow-up review. The other case is a 46-year-old male patient who was admitted to the hospital due to an intraorbital foreign body caused by a car accident, after which the patient was unconscious for approximately 6 h. After admission, the patient underwent emergency surgical treatment and postoperative anti-infection treatment. The patient could correctly answer questions at a 3-mo follow-up review.CONCLUSION Transorbital PBI is a rare and acute disease. Early diagnosis, surgical intervention, and application of intravenous antibiotics can improve the prognosis and quality of life of patients.

Autologous tenon capsule packing to treat posterior exit wound of penetrating injury: A case report

BACKGROUND This study reports a case of autologous tenon capsule packing to treat the posterior exit wound of penetrating injury.CASE SUMMARY To treat a 58-year-old male patient with penetrating eyeball injury caused by an iron sheet,we used autologous tenon capsule packing.Two months after removal of the silicone oil,the corrected visual acuity was 0.3,the retina was flat,the tenon capsule graft was in place,the posterior wound closed well,and the intraocular pressure was 15.8 mmHg.CONCLUSION Autologous tenon capsule packing to treat the posterior exit wound of penetrating injury is safe and effective.

Wooden stick penetration from the perineal region up to the thorax

BACKGROUND: Penetrating injuries of the perineum are rare but very dangerous. Since the genitourinary and colorectal organs may be injured, how to evaluate surgical management of the injury is very important.METHODS: The present report presents a case of penetrating injury of the perineum by a wooden stick when the patient fell on the upright wooden stick from a tree. The three feet long stick entered the perineal region just left lateral to the anal opening. Upon reaching the thoracic cavity, it broke and only a foot stick was left in the subcutaneous plane. These injuries are potentially serious with risk of damage to multiple organs. Exploratory laprotomy was done, and bladder injury was repaired. The entry wound and the track of stick was thoroughly washed and allowed for secondary intention healing.RESULTS: The post operative period was uneventful and the patient recovered fully.CONCLUSION: Meticulous evaluation and surgical management of perineal injuries are the key to prevent devastating complications.

Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

AIM： To compare the effects of intravitreal anti-vascular endothelial growth factor（VEGF） and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury.METHODS： Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1^st, 3^rd, 7^th, 14^th and 28^th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically.RESULTS： The median clinical score on the 14 th and 28 th days and the median macroscopic score of the dexamethasone group was significantly better than that of control（P=0.004, 0.018）. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively（P=0.476）. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance（P=0.538）. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION： This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

Subclavian Artery Pseudoaneurysm following Stab Injury and Its Surgical Approach: A Case Report and Literature Review

Penetrating injuries to the subclavian arteries as well as post traumatic pseudoaneurysm involving Subclavian artery (SCA) are very much uncommon. We present one case of a 21 year-old male sustained a physical assault with a post stab injury left subclavian artery pseudoaneurysm. He was referred to our facility, two days after sustaining a penetrating chest trauma over left infraclavicular area of the chest. The presentation, diagnostic procedures and surgical approach for management of this very rare injury are discussed.

About an Observation of a Child Penetrating Brain Injury by Knife

Background: Reported cases of knife injuries to the head in children are rare. Here we describe a case of pediatric penetrating brain injury by knife (PPBIK) and review literature. The patient’s parents were informed that non-identifying information from the case would be submitted for publication, and they provided consent. Case Presentation: A 3-year-old boy presented to our emergency department with a knife penetrating the front of his head during play. Neurologic examination was normal. Radiograph in lateral view demonstrated a metallic knife entering frontal bone. Computed tomography (CT) scan showed small hemorrhage around the foreign body recognized, accompanied by small pneumocephalus. The knife was surgically removed and the dura was closed. He was discharged home after the surgery with normal neurological status. Conclusion: Only four cases of PPBIK have been reported in the literature. The adequate management of these types of injuries requires a correct neuroradiological evaluation.

Severe Cut Throat Injury in a Child: A Case Report and Review of Literature

Background: Cut-throat injury is a potentially fatal condition that may be associated with serious morbidity and mortality. The neck region is particularly at risk of serious injuries due to the location of vital structures, including nerves, viscera, and major vessels. Although cut-throat injury is said to be rare in children, its occurrence has been reported in some series. Management of this condition requires a multidisciplinary approach for a better outcome. Aim: The aim of this report is to highlight the successful management of an alarming case of severe cut-throat injury with associated laryngeal injury in a child. Case presentation: A 12-year-old boy presented with a cut-throat following an assault by an unknown person. Examination revealed an acutely ill child, conscious but pale. He sustained a deep transverse laceration that transected the thyroid cartilage, exposing the laryngeal cavity. An assessment of Zone II penetrating neck injury was made. He was resuscitated, and had emergency neck exploration, tracheostomy, and repair of the injuries. The patient was followed up for 6 months, and had a good voice outcome, with no significant complication. Conclusion: Cut-throat injury is rare in children. But it is a potentially life-threatening condition. It is therefore important to recognize this entity and develop effective protocol of management in our environment.

Intralenticular metallic foreign body: a case report

A case of retained intralenticular iron piece with signs of mild anterior uveitis at the time of presentation is reported in a 45 year-old man. His vision improved with topical cycloplegics and corticosteroids. After six months, his vision deteriorated grossly due to cataract formation. He regained good vision following removal of foreign body, extracapsular extraction with posterior chamber intraocular lens implantation. This case highlights the conservative management of the condition till the patient develops cataract resulting in visual disability; and good visual recovery following cataract surgery with intraocular lens implantation.

Tracheal tube misplacement in the thoracic cavity:A case report

BACKGROUND Penetrating neck injuries require prompt recognition,diagnosis and management of critical airways.This case demonstrates an emergent situation that a“medical negligence”was avoided with the aid of end-tidal carbon dioxide(ETCO2)waveform.CASE SUMMARY We report a case of malposition of the endotracheal tube into the right hemithoracic cavity for cervical knife trauma,resulting in pneumothorax.Tube placement was not confirmed during emergency airway management,and the patient was directly transferred to the emergency operation room.Assisted by ETCO2 and imaging examinations,the anesthetist timely noticed the absence of ETCO2 waveform and resolved this urgent situation before anesthesia induction.CONCLUSION This case emphasizes the necessity of ETCO2 waveform and/or X-ray confirmation of endotracheal intubation even in emergent situations.

Disappeared intralenticular foreign body:A case report

BACKGROUND Intralenticular foreign body is rarely encountered in ophthalmic practice.In most cases,subsequent traumatic cataract requires cataract surgery for visual rehabilitation.CASE SUMMARY A 35-year-old man was injured by iron filings in his left eye.After the injury,the patient tried to draw the object out by himself using a magnet;however,the foreign body(FB)was pushed to the equator of the lens.The FB was removed by a magnet through the anterior chamber accessed through the original capsular wound.Since most of the lens was transparent and only partially opaque after the operation,the lens was kept under close observation.After the surgery,the patient’s visual acuity reached 20/20 from 2/20,visual function recovered very well,and local opacity of the lens remained stable.CONCLUSION For intralenticular FB in the anterior cortex under the capsule,magnet may be a more advantageous way to remove the object.

Surgical Management of Herniated Intrathoracic Gastric Perforation in Traumatic Diaphragmatic Rupture: An Unusual Two Rare Cases

Gastric perforation into the thoracic cavity through a diaphragmatic rupture is rare but, when it occurs, patients present in severe distress, with mortality approaching 50%. We present our experience of two rare and unusual cases of traumatic diaphragmatic rupture from penetrating chest injury associated with herniated intrathoracic gastric perforation over a five-year period from January 2015 to December 2020 at the cardiovascular and thoracic surgery department of the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Both patients underwent successful surgical repair through standard posterolateral thoracotomy with one having earlier negative exploratory laparotomy. The essence of the paper is to share and discuss the clinical presentation, diagnostic challenges, surgical management and the postoperative care of this very rare complication of traumatic diaphragmatic rupture.

Trans-base and trans-vault low-velocity penetrating brain injury:A retrospective comparative study of characteristics,treatment,and outcomes

Low-velocity penetrating brain injury(LVPBI)caused by foreign bodies can pose life-threatening emergencies.Their complexity and lack of validated classification data have prevented standardization of clinical management.We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type.;A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted.We included LVPBI patients admitted for the first time for surgery,and excluded those with multiple injuries,gunshot wounds,pregnancy,severe blunt head trauma,etc.Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway.Discharged patients were followed up by outpatient visit or telephone.The data were entered into the Electronic Medical Record system by clinicians,and subsequently derived by researchers.The demography and injury characteristics,treatment protocols,complications,and outcomes were analyzed and compared between the two groups.A t-test was used for analysis of normally distributed data,and a Mann-Whitney U test for non-parametric data.A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor.;A total of 27 LVPBI patients were included in this analysis,comprised of 13(48.1%)trans-base cases and 14(51.9%)trans-vault cases.Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds;while the trans-vault phenotype was correlated with injury by metal foreign bodies.There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups.Surgical approaches in the trans-base LVPBI group included subfrontal(n=5,38.5%),subtemporal(n=5,38.5%),lateral fissure(n=2,15.4%),and distal lateral(n=1,7.7%).All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference(n=14,100%).Moreover,the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment.Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries;in contrast,trans-vault LVPBI was associated with lower functional outcome scores.;Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics,treatment,and outcomes.Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Rational design of secondary operation for penetrating head injury:A case report

Penetrating head injury is rare,and thus management of such injuries is non-standard.Early diagnosis and intraoperative comprehensive exploration are necessary considering the complexity and severity of the trauma.However,because of the lack of microsurgical techniques in local hospitals,the possible retained foreign bodies and other postoperative complications such as cerebrospinal fluid(CSF)leak usually require a rational design for a secondary operation to deal with.We present a case of a 15-year-old boy who was stabbed with a bamboo stick in his left eye.The chopsticks passed through the orbit roof and penetrated the skull base.In subsequent days,the patient sustained CSF leak and intracranial infection after an unsatisfied primary treatment in the local hospital and had to request a secondary operation in our department.Computed tomography including plain scan,three dimension recon-struction and computed tomographic angiography are used to determine the course and extent of head injury.A frontal craniotomy was performed.Three pieces of stick were found residual and removed with the comminuted orbit bone fragments.A pedicled temporalis muscle fascia graft was applied to repair the frontier skull base and a free temporalis muscle flap to seal the frontal sinus defect.Aggressive broad-spectrum antibiotics of vancomycin and meropenem were administrated for persistent fever after operation.CSF external drainage system continued for 12 days,and was removed 10 days after tem-perature returned to normal.The Glasgow coma scale score was improved to 15 at postoperative day 7 and the patient was discharged at day 22 uneventfully.We believe that appropriate preoperative surgical plan and thorough surgical exploration by microsurgery is essential for attaining a favorable outcome,especially in secondary operation.Good postoperative recovery depends on successfully management before and after operation for possible complications as well.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries

Purpose:To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees’performance for emergent and urgent thoracic surgeries.Methods:With a homemade machine,animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage,urgent sternotomy,and emergent thoracotomy.Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models.Five operation teams from basic-level hospitals(group A)and five operation teams from level III hospitals(group B)were included to be trained and tested.Testing standards for the operations were established after thorough literature review,and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards.Tests were carried out after the training.Pre-and post-training performances were compared.Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches.Results:Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%.After literature review,testing standards were established,and expert questionnaire results showed that the scientific score was 7.30±1.49,and the feasibility score was 7.50±0.89.Post-training performance was significantly higher in both group A and group B than pre-training performance.Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury.Conclusions:Animal model-based simulation training established in the current study could improve the trainees’performance for emergent and urgent thoracic surgeries,especially of the surgical teams from basic-level hospitals.

Civilian gunshot wounds to the head:a case report,clinical management,and literature review

Background:Civilian gunshot wounds to the head refer to brain injury caused by projectiles such as gun projectiles and various fragments generated by explosives in a power launch or explosion.Gunshot wounds to the head are the deadliest of all gun injuries.According to literature statistics,the survival rate of patients with gunshot wounds to the head is only 9%.Due to the strict management of various types of firearms,they rarely occur,so the injury mechanism,injury and trauma analysis,clinical management,and surgical standards are almost entirely based on military experience,and there are few related reports,especially of the head,in which an individual suffered a fatal blow more than once in a short time.We report a case with a return to almost complete recovery despite the patient suffering two gunshot injuries to the head in a short period of time.Case presentations:We present a case of a 53-year-old man who suffered two gunshot injuries to the head under unknown circumstances.On initial presentation,the patient had a Glasgow Coma Scale score of 6,was unable to communicate,and had loss of consciousness.The first bullet penetrated the right frontal area and finally reached the right occipital lobe.When the patient reflexively shielded his head with his hand,the second bullet passed through the patient’s right palm bone,entered the right frontotemporal area,and came to rest deep in the lateral sulcus.The patient had a cerebral hernia when he was admitted to the hospital and immediately entered the operating room for rescue after a computed tomography scan.After two foreign body removals and skull repair,the patient recovered completely.Conclusions:Gunshot wounds to the head have a high mortality rate and usually require aggressive management.Evaluation of most gunshot injuries requires extremely fast imaging examination upon arrival at the hospital,followed by proactive treatment against infection,seizure,and increased intracranial pressure.Surgical intervention is usually necessary,and its key points include the timing,method,and scope of the operation.

Microsurgical repair of severed thoracic spinal cord and clinical outcome:technical case report

Background:This report describes a case of successful repair of severed thoracic spine in a young man who presented with a penetrating stab injury to spine resulting in Brown-Séquard syndrome.Surgical technique and postoperative management is discussed.Case presentation:A 34-year-old fit and well healthy man was admitted with a history of stab injury to the thoracic spine at thoracic T2/3 level with ASIA impairment score(AIS)score D with an incomplete spinal cord affecting his left lower limb with complete paralysis and right lower limb paresis with impaired sensation below T6 level to L5.Neuroimaging confirmed a penetrating knife injury traversing the T2/3 level causing hemi-section of the spinal cord confirmed intraoperatively.He underwent an urgent exploratory surgery of his spine and a T2/3 laminectomy was performed to aid removal of the knife.The dura was noted to be contused and severed spinal cord was noted to be severed with associated cord oedema.A microsurgical repair of the severed cord was performed with duroplasty followed by intense neuro-rehabilitation.On a 3 month follow up his AIS score is E with lower limb power is 5/5 bilaterally and he is able to mobilise independently up to 8-10 steps without any supportive aid and with crutches he is independently functional and mobile.Conclusion:This is the first documented case of microsurgical repair of severed thoracic spinal cord secondary to traumatic knife injury.In the management of such scenario,apart from the removal of foreign body,repair of the cord with duroplasty should be carefully considered.The role of spinal neuroplasticity in healing following timely repair of the spinal cord along with intense rehabilitation remains the key.This had resulted in a good clinical and functional outcome with in a 18-month follow up.