Focal Contusion Research Articles

Возможности низкоинтенсивного лазерного облучения крови и аспекты доказательности его эффективности в лечении контузионных очагов и внутричерепных гематом малого объёма

Возможности низкоинтенсивного лазерного облучения крови и аспекты доказательности его эффективности в лечении контузионных очагов и внутричерепных гематом малого объёма

Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury.

Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D–mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. In vivo animal experiments have demonstrated neuroprotective effects of cyclosporine in more than 20 independent experimental studies in a multitude of different experimental models. However, the majority of these studies have been carried out in rodents. The aim of the present study was to evaluate the efficacy of a novel and cremophor/kolliphor EL–free lipid emulsion formulation of cyclosporine in a translational large animal model of TBI. A mild-to-moderate focal contusion injury was induced in piglets using a controlled cortical impact device. After initial step-wise analyses of pharmacokinetics and comparing with exposure of cyclosporine in clinical TBI trials, a 5-day dosing regimen with continuous intravenous cyclosporine infusion (20 mg/kg/day) was evaluated in a randomized and blinded placebo-controlled setting. Cyclosporine reduced the volume of parenchymal injury by 35%, as well as improved markers of neuronal injury, as measured with magnetic resonance spectroscopic imaging. Further, a consistent trend toward positive improvements in brain metabolism and mitochondrial function was observed in the pericontusional tissue. In this study, we have demonstrated efficacy using a novel cyclosporine formulation in clinically relevant and translatable outcome metrics in a large animal model of focal TBI.

Traumatic Brain Injury in Aged Mice Induces Chronic Microglia Activation, Synapse Loss, and Complement-Dependent Memory Deficits.

Traumatic brain injury (TBI) is of particular concern for the aging community since there is both increased incidence of TBI and decreased functional recovery in this population. In addition, TBI is the strongest environmental risk factor for development of Alzheimer’s disease and other dementia-related neurodegenerative disorders. Critical changes that affect cognition take place over time following the initial insult. Our previous work identified immune system activation as a key contributor to cognitive deficits observed in aged animals. Using a focal contusion model in the current study, we demonstrate a brain lesion and cavitation formation, as well as prolonged blood–brain barrier breakdown. These changes were associated with a prolonged inflammatory response, characterized by increased microglial cell number and phagocytic activity 30 days post injury, corresponding to significant memory deficits. We next aimed to identify the injury-induced cellular and molecular changes that lead to chronic cognitive deficits in aged animals, and measured increases in complement initiation components C1q, C3, and CR3, which are known to regulate microglial–synapse interactions. Specifically, we found significant accumulation of C1q on synapses within the hippocampus, which was paralleled by synapse loss 30 days post injury. We used genetic and pharmacological approaches to determine the mechanistic role of complement initiation on cognitive loss in aging animals after TBI. Notably, both genetic and pharmacological blockade of the complement pathway prevented memory deficits in aged injured animals. Thus, therapeutically targeting early components of the complement cascade represents a significant avenue for possible clinical intervention following TBI in the aging population.

Prevalence, Patterns, and Clinical Relevance of Hypoxic-Ischemic Injuries in Children Exposed to Abusive Head Trauma.

Hypoxic-ischemic injuries (HIIs) are a scarcely investigated but important cause of morbidity and mortality in children who suffered abusive head trauma (AHT). The purpose of this study is to determine: (a) prevalence, types, and clinical relevance of cytotoxic edema compatible with HII in nonpenetrating AHT, (b) their relationship to other classic neuroimaging findings of AHT, and (c) their correlation with clinical outcomes. Diffusion-weighted imaging sequences of magnetic resonance imagings performed on children under 5 years diagnosed with AHT were reviewed to detect the most common patterns of acute parenchymal damage. Patterns of cytotoxic edema were described, and HII-compatible ones divided in subtypes. Correlation between HII, fractures, and subdural hemorrhages (SDHs) and with clinical outcomes was determined using imaging and available follow-up data. Out of 57 patients, 36.8% showed lesions compatible with HII. A predominantly asymmetric cortical distribution was observed in 66.7% of cases, while 33.3% had diffused both cortical and deep gray/white matter distribution injury. Traumatic axonal injuries and focal contusions were less common. There was no significant correlation between the presence of SDH (P = .6) or skull fractures (P = .53) and HII. HII was the most severe form of parenchymal damage in terms of in-hospital mortality and morbidity at follow-up. HII is the most common type of parenchymal damage in children victim of AHT, being present in 1/3 of patients with this condition, and correlates with more severe outcomes. Its presence is independent from other classic traumatic findings such as SDH and fractures.

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-1β) 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-1β in both models.

Minimizing Retraction by Pia-Arachnoidal 10-0 Sutures in Intrasulcal Dissection.

In contemporary microneurosurgery reducing retraction-induced injury to the brain is essential. Self-retaining retractor systems are commonly used to improve visualization and decrease the repetitive microtrauma, but sometimes self-retaining retractor systems can be cumbersome and the force applied can cause focal ischemia or contusions. This may increase the morbidity and mortality. Here, we describe a technique of retraction using 10-0 sutures in the arachnoid. To evaluate the imaging and clinical results in patients where 10-0 suture retraction was used to aid the surgical procedure. Adjacent cortex was retracted by placing 10-0 nylon suture in the arachnoid of the bank or banks of the sulcus. The suture was secured to the adjacent dural edge by using aneurysm clips, allowing for easy adjustability of the amount of retraction. We retrospectively analyzed the neurological outcome, signal changes in postoperative imaging, and ease of performing surgery in 31 patients with various intracranial lesions including intracranial aneurysms, intra- and extra-axial tumors, and cerebral ischemia requiring arterial bypass. Clinically, there were no injuries, vascular events, or neurological deficits referable to the relevant cortex. Postoperative imaging did not show changes consistent with ischemia or contusion due to the retraction. This technique improved the visualization and illumination of the surgical field in all cases. Retraction of the arachnoid can be used safely in cases where trans-sulcal dissection is required. This technique may improve initial visualization and decrease the need for dynamic or static retraction.

A Lateral Fluid Percussion Injury Model for Studying Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) diagnoses have increased in frequency during the past decade, becoming a silent epidemic. The pathophysiology of TBI involves pathophysiological processes affecting the brain, induced by traumatic biomechanical forces resulting in temporary impairment of neurological function. Preclinical models have been generated to recapitulate the mechanical, neuroinflammatory, and behavioral outcomes observed in the clinical setting. The lateral fluid percussion (LFP) model is the most extensively used and well-characterized model of nonpenetrating and nonischemic TBI. The model is reproducible and can be adjusted to produce a mild to moderate and severe injury, as reflected by mortality and return of reflexes, by adjusting the amount of force applied. The histopathological changes achieved with this model reproduce that seen in human TBI including focal contusion in the cortex, with accompanying intraparenchymal punctate hemorrhage, followed by inflammation and neuronal degeneration. This chapter describes the LFP model, which produces a mixed model of focal and diffuse brain injury that progresses over time affecting predominantly the cortical parenchyma.

Distinct Myeloid Cell Subsets Promote Angiogenesis and Damaged Tissue Clearance Following Mild Traumatic Brain Injury

Abstract Mild traumatic brain injury (mTBI) leads to a robust immune response featuring resident microglia/macrophages and recruitment of peripherally-derived monocytes/macrophages. We sought novel insights into the dynamics and function of innate myeloid cells following brain injury by studying a closed-skull focal contusion model of mTBI that permits real-time imaging by intravital two-photon microscopy (TPM). TPM studies of CX3CR1GFP/+ CCR2RFP/+ reporter mice revealed an early microglia response followed by CCR2+ monocytes and CX3CR1+ macrophages that accumulated 1 to 7 days post-TBI. This transition coincided with dynamic changes in gene expression that shifted from pro-inflammatory to wound-healing. Early cell death and vascular destruction led to an impressive re-vascularization of the lesioned meninges, with 80–100% wound closure observed within 7 days of injury. We used histo-cytometry to define the anatomical position of the different myeloid subpopulations within the injured meninges during the repair phase. This revealed the presence of non-classical and resident macrophages that highly expressed the remodeling enzyme matrix metalloproteinase 2 (Mmp2) in the lesion core. Depletion of neutrophils and classical monocytes increased pathology due to inefficient dead cell clearance, but re-vascularization of the wound was not affected. Interestingly, vascular regeneration was significantly impaired only when non-classical monocytes and resident meningeal macrophages were depleted, resulting in reduced numbers of CD206+macrophages in the lesion. These studies demonstrate that neutrophils, monocytes, and resident macrophages participate in coordinated yet divergent wound-healing responses to mTBI.

Executive functioning of complicated-mild to moderate traumatic brain injury patients with frontal contusions

ABSTRACTExecutive dysfunctions are among the most prevalent neurobehavioral sequelae of traumatic brain injuries (TBIs). Using culturally validated tests from the Delis-Kaplan Executive Function System (D-KEFS: Trail Making, Verbal Fluency, Design Fluency, Sorting, Twenty Questions, and Tower) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS: Rule Shift Cards, Key Search, and Modified Six Elements), the current study was the first to examine executive functioning in a group of Iranian TBI patients with focal frontal contusions. Compared with a demographically matched normative sample, the frontal contusion patients showed substantial impairments, with very large effect sizes (p ≤ .003, 1.56 < d < 3.12), on all the executive measures. Controlling for respective lower-level/fundamental conditions, the differences on the highest-level executive (cognitive switching) conditions were still significant. The frontal patients also committed more errors. Patients with lateral prefrontal (LPFC) contusions were qualitatively worst. For example, only the LPFC patients committed perseverative repetition errors. Altogether, our results support the notion that the frontal lobes, specifically the lateral prefrontal regions, play a critical role in cognitive executive functioning, over and above the contributions of respective lower-level cognitive abilities. The results provide clinical evidence for validity of the cross-culturally adapted versions of the tests.

Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior.

Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior.

Brain Contusions and SUR1 Receptors: Has a New Target Been Born?

Figure 1. Post-traumatic brain contusions may increase in size and cause edema with consequent neurologic deterioration. Adequate knowledge of these mechanisms may improve final outcome. Traumatic brain injury (TBI) is the number 1 cause of death in trauma victims who reach the hospital alive. TBI is a complex, multifaceted disease. Among this population, intracerebral hemorrhage, or “brain contusion,” is a common finding. One of the most important and least studied is the serious problem of spatiotemporal progression of brain contusions. Also called posttraumatic brain contusions (PTBCs), these contusions are traditionally considered primary injuries, but they have an inherent capacity to increase in size, generate perilesional edema, cause mass effect, induce neurologic deterioration, and, in some patients, cause death (Figure 1). These lesions are frequently associated with volumetric expansion during the first 48 hours post trauma. In most patients, there is a progressive increase in pericontusional edema, and in nearly half of patients, there is an increase in the hemorrhagic component itself. Until recently, the underlying molecular pathophysiology of contusion-induced brain edema and hemorrhagic progression was poorly understood. However, new evidence has accumulated in the past decade and the complex cellular and molecular mechanisms underlying PTBCs volumetric increases have been better predictable. Since the works of Simard et al., in which newly expressed SUR1-regulated NC (Ca-ATP) channel mediates cerebral edema after ischemic stroke, more attention has been given to this protein and its blockade in brain injuries, especially traumatic brain lesions. The same author, in another study, induced focal cortical contusions in rats and the regulatory subunit of the channel, SUR1, was prominently upregulated in capillaries of penumbral tissues surrounding the contusion. Corroborating the previous findings, Martinez-Valverde et al. reported SUR1 expression in humans with PTBCs. They found that SUR1 was significantly upregulated in all types of brain cells with especially prominent increases in neurons, glia, and endothelial cells. Therapeutic management of PTBCs has been limited to date. The fact that SUR1 is upregulated in these lesions opens new opportunities (e.g., glyburide) to modulate the molecular cascades generated by these focal injuries.

Weight Drop Models in Traumatic Brain Injury.

Weight drop models in rodents have been used for several decades to advance our understanding of the pathophysiology of traumatic brain injury. Weight drop models have been used to replicate focal cerebral contusion as well as diffuse brain injury characterized by axonal damage. More recently, closed head injury models with free head rotation have been developed to model sports concussions, which feature functional disturbances in the absence of overt brain damage assessed by conventional imaging techniques. Here, we describe the history of development of closed head injury models in the first part of the chapter. In the second part, we describe the development of our own weight drop closed head injury model that features impact plus rapid downward head rotation, no structural brain injury, and long-term cognitive deficits in the case of multiple injuries. This rodent model was developed to reproduce key aspects of sports concussion so that a mechanistic understanding of how long-term cognitive deficits might develop will eventually follow. Such knowledge is hoped to impact athletes and war fighters and others who suffer concussive head injuries by leading to targeted therapies aimed at preventing cognitive and other neurological sequelae in these high-risk groups.

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

Impact Acceleration Model of Diffuse Traumatic Brain Injury.

The impact acceleration (I/A) model of traumatic brain injury (TBI) was developed to reliably induce diffuse traumatic axonal injury in rats in the absence of skull fractures and parenchymal focal lesions. This model replicates a pathophysiology that is commonly observed in humans with diffuse axonal injury (DAI) caused by acceleration-deceleration forces. Such injuries are typical consequences of motor vehicle accidents and falls, which do not necessarily require a direct impact to the closed skull. There are several desirable characteristics of the I/A model, including the extensive axonal injury produced in the absence of a focal contusion, the suitability for secondary insult modeling, and the adaptability for mild/moderate injury through alteration of height and/or weight. Furthermore, the trauma device is inexpensive and readily manufactured in any laboratory, and the induction of injury is rapid (~45 min per animal from weighing to post-injury recovery) allowing multiple animal experiments per day. In this chapter, we describe in detail the methodology and materials required to produce the rat model of I/A in the laboratory. We also review current adaptations to the model to alter injury severity, discuss frequent complications and technical issues encountered using this model, and provide recommendations to ensure technically sound injury induction.

Network analysis of human fMRI data suggests modular restructuring after simulated acquired brain injury.

The pathophysiology underlying neurocognitive dysfunction following mild traumatic brain injury (TBI), or concussion, is poorly understood. In order to shed light on the effects of TBI at the functional network or modular level, our research groups are engaged in the acquisition and analysis of functional magnetic resonance imaging data from subjects post-TBI. Complementary to this effort, in this paper we use mathematical and computational techniques to determine how modular structure changes in response to specific mechanisms of injury. In particular, we examine in detail the potential effects of focal contusions, diffuse axonal degeneration and diffuse microlesions, illustrating the extent to which functional modules are preserved or degenerated by each type of injury. One striking prediction of our study is that the left and right hemispheres show a tendency to become functionally separated post-injury, but only in response to diffuse microlesions. We highlight other key differences among the effects of the three modelled injuries and discuss their clinical implications. These results may help delineate the functional mechanisms underlying several of the cognitive sequelae associated with TBI.

Predictors of Hypopituitarism in Patients with Traumatic Brain Injury.

Hypopituitarism may often occur in association with traumatic brain injury (TBI). Identification of reliable predictors of pituitary dysfunction is of importance in order to establish a rational testing approach. We searched the records of patients with TBI, who underwent neuroendocrine evaluation in our institution between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months (0.2-430.4).Of these, 31% had ≥1 pituitary deficiency, including 29% of patients with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were more likely to have suffered a motor vehicle accident (MVA, p = 0.04), experienced post-traumatic seizures (p = 0.04), demonstrated any intracranial hemorrhage (p = 0.05), petechial brain hemorrhages (p = 0.017), or focal cortical parenchymal contusions (p = 0.02). Central hypothyroidism occurred in 8% and central hypogonadism in 12%; the latter subgroup had higher BMI (p = 0.03), were less likely to be working after TBI (p = 0.002), and had lower Global Assessment of Functioning (GAF) scores (p = 0.03). Central diabetes insipidus (DI) occurred in 6%, who were more likely to have experienced MVA (p < 0.001) or sustained moderate/severe TBI (p < 0.001). Patients with MVA and those with post-traumatic seizures, intracranial hemorrhage, petechial brain hemorrhages, and/or focal cortical contusions are at particular risk for serious pituitary dysfunction, including adrenal insufficiency and DI, and should be referred for neuroendocrine testing. However, a substantial proportion of patients without these risk factors also developed hypopituitarism.

Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in the female rat.

Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.

ApoE and S-100 expression and its significance in the brain tissue of rats with focal contusion.

This study explored the effect of focal cerebral contusion on the expression of ApoE and S-100, and its significance in determining the time of brain injury. Based on a rat model of cerebral contusion, immunohistochemistry was used to analyze the expressions of S-100 and ApoE at different time points after injury. Thirty minutes following cerebral contusion, ApoE protein expression was significantly increased in cortex neurons (P < 0.01), and S-100 protein expression was significantly (P < 0.001) elevated 2 h after cerebral contusion. Over time, the number of ApoE and S-100 positively expressing cells gradually increased. Three days after injury, ApoE was widely distributed throughout the tissue and the number of ApoE-positive cells and staining intensity reached a peak. ApoE expression decreased after this time point. Five days after cerebral contusion, the number of S-100-positive cells reached a peak level of expression higher than that in the control group. Our data demonstrate that the expression of ApoE and S-100 correlated with the progression of focal cerebral contusion. This suggests that both proteins may serve as effective biomarkers of focal cerebral contusions.

Secondary hemorrhagic progression of contusion foci in patients with traumatic brain injury

Introduction. Secondary posttraumatic changes of the brain often are determining in the clinical flow of traumatic brain injury (TBI). Prevention, detection and determination of treatment strategy at secondary hemorrhagic progression of contusion (SHPC) are very actual for neurotraumatology. Materials and methods. The results of 110 injured persons with TBI were analyzed. Results. It was found that SHPC occurs in 50% patients with TBI, as in areas of primary brain damage as in remote areas on the other side of the brain during 12 h ad also after 3–4 days. SHPC often is revealed in patients with subdural hematoma. The bigger contusion foci, the higher the probability of their progression and the need of surgical decompression. Conclusions. SHPC is one of most important TBI complications associated with considerable risk of clinical deterioration and serious cause of morbidity and lethality. Treatment tactics depends on severity of volumetric effect on surrounding brain structures and manifestations of compression-dislocation syndrome.

An examination of co-occurring conditions and management of psychotropic medication use in soldiers with traumatic brain injury.

There are approximately 1.4 million cases of traumatic brain injury (TBI) per year in the United States, with about 23 000 survivors requiring hospitalization. The incidence of TBI has increased in the patient population of the Department of Defense and Veterans Healthcare Administration as a result of injuries suffered during recent military and combat operations. Within the past few years, TBI has emerged as a common form of injury in service members with a subset of patients experiencing postinjury symptoms that greatly affect their quality of life. Traumatic brain injury can occur when sudden trauma (ie, penetration blast or blunt) causes damage to the brain. Traumatic brain injury produces a cascade of potentially injurious processes that include focal contusions and cytotoxic damage. The results of TBI can include impaired physical, cognitive, emotional, and behavioral functioning, which may or may not require the initiation of pharmacological and nonpharmacological interventions when deemed appropriate. Associated outcomes of TBI include alterations in mental state at the time of injury (confusion, disorientation, slowed thinking, and alteration of consciousness). Neurological deficits include loss of balance, praxis, aphasia, change in vision that may or may not be transient. Individuals who sustain a TBI are more likely to have or developed co-occurring conditions (ie, sleep problems, headaches, depression, anxiety, and posttraumatic stress disorder) that may require the administration of multiple medications. It has been identified that veterans being discharged on central nervous system and muscular skeletal drug classes can develop addiction and experience medication misadventures. With the severity of TBI being highly variable but typically categorized as either mild, moderate, or severe, it can assist health care providers in determining which patients are more susceptible to medication misadventures compared with others. The unique development of cognitive and emotional symptoms of TBI can lead to significant impairments, so it is important for all health care providers, including pharmacists, to promote proper use of high-risk psychotropic medications among this patient population by providing effective medication education.