Treatment Of Brain Injury Research Articles

TNFAIP3 affects ferroptosis after traumatic brain injury by affecting the deubiquitination and ubiquitination pathways of the HMOX1 protein and ACSL3.

The occurrence and progression of traumatic brain injury involve a complex process. The pathophysiological mechanisms triggered by neuronal damage include various forms of programmed cell death, including ferroptosis. We observed upregulation of TNFAIP3 in mice after traumatic brain injury. Overexpression of TNFAIP3 inhibits HT-22 proliferation and cell viability through ferroptosis. Mechanistically, TNFAIP3 interacts with the HMOX1 protein and promotes its stability through the deubiquitination pathway. Additionally, TNFAIP3 can enhance lipoperoxidation, mitochondrial damage, and neuronal cell death by promoting ACSL3 degradation via NEDD4-mediated ubiquitination. Mice injected with AAV-shTNFAIP3 exhibited reduced neuronal degeneration and improved motor and cognitive function following cortical impact injury. In conclusion, our findings demonstrate that TNFAIP3 deficiency inhibits neuronal cell ferroptosis and ameliorates cognitive impairment caused by traumatic brain injury and demonstrate its potential applicability in the treatment of traumatic brain injury.

Brain-targeted M2 macrophage membrane-hybrid biomimetic liposomes for treatment of traumatic brain injury.

Traumatic brain injury (TBI) is highly incidental but effective solutions are absent. Moreover, the secondary injury following TBI is arising due to the Ca2+ influx of injured neural cells. Here, a Ca2+ influx inhibitor, nimodipine, was loaded in M2 macrophage membrane-hybrid biomimetic liposomes (NM2Ls). NM2Ls significantly inhibited the influx of Ca2+ into inflammatory neural cells and reduced the expression of inflammatory factors. More importantly, intravenously injected NM2Ls avoided the clearance of the immune system and targeted the brain via CCR2 following TBI; the inflammation in the brain was greatly alleviated in the TBI mouse model. NM2Ls improved the long-term learning and memory abilities as well as the motor abilities of TBI mice. Oxidative stress indicators were reduced and the repair of nerve cells was improved. NM2Ls is a promising brain-targeted medicine by the biomembrane biomimetic strategy.

Human Neural Stem Cell Therapy for Traumatic Brain Injury-A Systematic Review of Pre-Clinical Studies.

Human neural stem cells (hNSCs) possess significant therapeutic potential for the treatment of traumatic brain injury (TBI), a leading cause of global death and disability. Recent pre-clinical studies have shown that hNSCs reduce tissue damage and promote functional recovery through neuroprotective and regenerative signaling and cell replacement. Yet the overall efficacy of hNSCs for TBI indications remains unclear. Therefore, this systematic review aims to evaluate hNSC interventions compared with controls in pre-clinical TBI models. Through this process, variations in hNSC administration protocols were consolidated, and key knowledge gaps were identified. Meta-analysis was applied to primary outcomes of lesion volume, Morris Water Maze (MWM) performance, modified Neurological Severity Scores (mNSS), and the rotarod task. Narrative review of secondary outcomes included hNSC survival and differentiation, endogenous neuron survival, axonal injury, and inflammation. Overall, hNSC intervention reduced lesion volume, enhanced MWM performance, and led to trending decreases in acute and chronic neurological deficits at acute and chronic time points. These results suggest hNSCs demonstrate clear efficacy in pre-clinical TBI models. However, further studies are needed to address key questions regarding optimal hNSC administration (e.g., dosing, treatment window) and underlying mechanisms of action prior to progressing to human clinical trials.

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients as an anesthetic and a neuroprotectant used for treating brain injuries. Xe penetrates the blood-brain barrier, which could make it an effective therapeutic. To assess the effect of Xe on microglia and AD pathology, we designed a custom Xe inhalation chamber and treated several mouse models of AD with Xe gas. Xe treatment induced mouse microglia to adopt an intermediate activation state that we have termed pre-neurodegenerative microglia (pre-MGnD). This microglial phenotypic transition was observed in mouse models of acute neurodegeneration and amyloidosis (APP/PS1 and 5xFAD mice) and tauopathy (P301S mice). This microglial state enhanced amyloid plaque compaction and reduced dystrophic neurites in the APP/PS1 and 5xFAD mouse models. Moreover, Xe inhalation reduced brain atrophy and neuroinflammation and improved nest-building behavior in P301S mice. Mechanistically, Xe inhalation induced homeostatic brain microglia toward a pre-MGnD state through IFN-γ signaling that maintained the microglial phagocytic response in APP/PS1 and 5xFAD mice while suppressing the microglial proinflammatory phenotype in P301S mice. These results support the translation of Xe inhalation as an approach for treating AD.

Modulating Ferroptosis: A Novel Approach to Promote Neural Repair in Brain Injury.

The increasing prevalence of brain injuries resulting in cognitive and motor function impairments poses a substantial global medical challenge. Nerve repair therapies offer promise for addressing brain injury-related disorders. Ferroptosis, as a cell death mechanism associated with oxidative stress and inflammation. Certain ferroptosis inhibitors, such as iron chelators and antioxidants, exhibit therapeutic potential for brain injury-related conditions. This review explores the fundamental processes and associated mechanisms that regulate neural repair by inhibiting ferroptosis, thereby alleviating brain injury and promoting neuroregeneration. Furthermore, it examines the action mechanisms and potential therapeutic applications of ferroptosis inhibitors in neural repair, aiming to provide novel insights for treating brain injuries.

Applications of hydrogels and nanoparticles in the treatment of traumatic brain injury.

Traumatic brain injury (TBI) represents a significant global public health issue, with effective management posing numerous challenges. The pathophysiology of TBI is typically categorized into two phases: primary and secondary injuries. Secondary injury involves pathophysiological mechanisms such as blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, and inflammatory responses. Current pharmacological strategies often encounter obstacles in treating TBI effectively, primarily due to challenges in BBB penetration, inadequate target site accumulation, and off-target toxicity. Versatile hydrogels and nanoparticles offer potential solutions to these limitations. This review discusses recent progress in utilizing hydrogels and nanoparticles for TBI treatment over the past 5years, highlighting their relevance to the underlying injury pathophysiology. Hydrogels and nanoparticles demonstrate substantial promise in addressing secondary brain injury, providing a broad spectrum of future therapeutic opportunities.

Vitamin therapy in the treatment of mild traumatic brain injury: new horizons of clinical practice

Objective: To investigate the main aspects of the impact of vitamin therapy on the treatment effectiveness of patients with mild traumatic brain injury and to illustrate it on the example of individual clinical cases. Materials and Methods. The analysis of scientific sources of information in various electronic databases (PUBMED, ScienceDirect, Reserch4life, MEDLINE) on the ability of vitamins to reduce oxidative stress, stimulate neuroprotection, and improve cognitive function in people with mild traumatic brain injury over the past 10 years. The search included the following keywords and terms: vitamins (with separate letters B, C, D, E) and omega-3 fatty acids, mTBI, TBI, oxidative stress, micronutrients, physiological process, cognitive function, and biochemical and neurological consequences. To describe clinical cases, in addition to the well-known methods of examination of patients with mild traumatic brain injury, scales for assessing the psychoemotional state were used, namely the Hospital Anxiety and Depression Scale (HADS) for patients in somatic inpatient departments. Results. According to scientific sources of information, a positive effect of vitamins C, E and D on reducing oxidative stress was demonstrated, while B vitamins contributed more to the normalization of neuronal energy metabolism. Patients with mild traumatic brain injury treated with complex vitamin therapy demonstrated a reduction in the duration of mild traumatic brain injury symptoms, in particular headache, and improvement of psychoemotional state, mainly during the first 10 days of treatment. Conclusions. Since traumatic brain injury (TBI) is a complex clinical condition accompanied by both primary brain damage and a secondary biochemical cascade that contributes to prolonged neuroinflammation, oxidative stress, and cellular dysfunction, its treatment and rehabilitation require the development of new approaches, in particular with the use of vitamin therapy, which aims to support the function of the nervous system by providing neuroprotection, antioxidant action, and support for cellular energy metabolism. Clinical examples demonstrate a phenomenological tendency to a more pronounced recovery of the psycho-emotional state in a patient who was prescribed thiamine hydrochloride 100 mg, pyridoxine hydrochloride 100 mg, cyanocobalamin 1 mg (Vitaxon) by mouth once daily. The data from preclinical and clinical studies in recent years confirm the prospects of using vitamin supplements as part of the complex therapy of mild traumatic brain injury to reduce secondary brain damage, improve cognitive function, and accelerate patient recovery. Further research of the mechanisms of action of vitamins, optimal dosages, time windows of use, and impact on long-term outcomes is needed to improve the treatment of patients with mild traumatic brain injury, which may become an important component of personalized TBI therapy aimed at reducing functional deficits and improving patients' quality of life.

Unravelling Secondary Brain Injury: Insights from a Human-Sized Porcine Model of Acute Subdural Haematoma.

Traumatic brain injury (TBI) remains one of the leading causes of death. Because of the individual nature of the trauma (brain, circumstances and forces), humans experience individual TBIs. This makes it difficult to generalise therapies. Clinical management issues such as whether intracranial pressure (ICP), cerebral perfusion pressure (CPP) or decompressive craniectomy improve patient outcome remain partly unanswered. Experimental drug approaches for the treatment of secondary brain injury (SBI) have not found clinical application. The complex, cellular and molecular pathways of SBI remain incompletely understood, and there are insufficient experimental (animal) models that reflect the pathophysiology of human TBI to develop translational therapeutic approaches. Therefore, we investigated different injury patterns after acute subdural hematoma (ASDH) as TBI in a post-hoc approach to assess the impact on SBI in a long-term, human-sized porcine TBI animal model. Post-mortem brain tissue analysis, after ASDH, bilateral ICP, CPP, cerebral oxygenation and temperature monitoring, and biomarker analysis were performed. Extracerebral, intraparenchymal-extraventricular and intraventricular blood, combined with brainstem and basal ganglia injury, influenced the experiment and its outcome. Basal ganglia injury affects the duration of the experiment. Recognition of these different injury patterns is important for translational interpretation of results in this animal model of SBI after TBI.

Acute Treatment with Fucoidan Ameliorates Traumatic Brain Injury-Induced Neurological Damages and Memory Deficits in Rats: Role of BBB Integrity, Microglial Activity, Neuroinflammation, and Oxidative Stress.

There is no acquiesced remedy for the treatment of traumatic brain injury (TBI)-associated impairment, especially cognitive decline. The first 24h after TBI is a golden time for preventing the progress of the impairments. The present study aimed to examine the acute effects of fucoidan on neurological outcomes and memory performance and investigate its potential mechanisms in rats with TBI. Fucoidan (25, 50, and 100mg/kg, i.p.) was injected immediately after TBI induction. Veterinary coma scale (VCS), brain edema, blood-brain barrier (BBB) integrity, passive avoidance memory and spatial memory, neuroplasticity, myeloperoxidase (MPO) activity, oxidative stress, and histological alteration were evaluated after TBI induction and fucoidan treatment. The findings revealed that TBI resulted in an enhancement in brain water content and BBB permeability and diminished the performance of passive avoidance memory and spatial memory. These were accompanied by long-term potentiation (LTP) suppression in the hippocampus and the prevention of activities of SOD, catalase, and GPx and enhancement of MPO activity, TNF-α, IL-6, and lipid peroxidation levels in the hippocampus as well as hippocampal neuronal loss. Fascinatingly, acute treatment of TBI rats with fucoidan especially in the higher doses (50 and 100mg/kg) significantly ameliorated (p < 0.05) neurological outcomes of VCS, cerebral edema, BBB integrity, passive avoidance memory, spatial memory, LTP impairment, and oxidative-antioxidative balance. Also, fucoidan significantly ameliorated hippocampal neuronal loss, TNF-α and IL-6 levels, and MPO activity as an indicator of microglial activation. These outcomes imply that fucoidan can be a hopeful remedy for TBI-associated neuronal impairments. However, further research is necessary to endorse this issue.

CXCR2 immunomodulatory therapy protects against microstructural white matter injury and gait abnormalities but does not mitigate deficits of cognition in a preclinical model of cerebral palsy.

Minimizing central nervous system (CNS) injury from preterm birth depends upon understanding the critical pathways that underlie essential neurodevelopmental and CNS pathophysiology. Signaling by chemokine (C-X-C motif) ligand 1 (CXCL1) through its cognate receptor, CXCR2 [(C-X-C motif) receptor 2] is essential for neurodevelopment. Increased CXCR2 signaling, however, is implicated in a variety of uterine and neuropathologies, and their role in the CNS injury associated with perinatal brain injury is poorly defined. To evaluate the long-term efficacy of CXCR2 blockade in functional repair of brain injury secondary to chorioamnionitis (CHORIO), we used an established preclinical rat model of cerebral palsy. We tested the hypothesis that transient postnatal CXCR2 antagonism with SB225002 would reduce gait deficits, hypermobility, hyperactivity, and disinhibition concomitant with repair of functional and anatomical white and gray matter injury. CHORIO was induced in pregnant Sprague Dawley rats on embryonic day 18 (E18). SB225002 (3 mg/kg) was administered intraperitoneally from postnatal day 1 (P1)-P5. Rats were aged to adulthood and tested for gait, open-field behavior and cognitive and executive function deficits using a touchscreen cognitive assessment platform. Results show that transient CXCR2 blockade attenuated microstructural white matter injury after CHORIO consistent with improved anatomical connectivity, and mitigated deficits in gait coordination, posture, balance, paw placement, and stepping (p < 0.05). Animals with CHORIO were hyperactive and hypermobile with fMRI deficits in neural circuitry central to cognition. However, CXCR2 antagonism in CHORIO animals did not normalize open-field behavior, neural activity, or cognition on a touchscreen task of discrimination learning (all p > 0.05). Studies in CXCR2 knockout mice confirmed significantly impaired cognitive performance independent of CHORIO. Taken together, transient postnatal blockade of CXCR2 ameliorates aspects of the lasting neural injury after CHORIO including normalizing gait deficits and white matter injury. However, improvement in essential functional and cognitive domains are not achieved limiting the utility of this therapeutic approach for treatment of perinatal brain injury. This study emphasizes the complex, multi-faceted role of chemokines in typical neurodevelopment, circuit formation, neural network function, and injury response.

Current advances in treatment for traumatic brain injury

Background: Traumatic brain injury (TBI) refers to a disruption in brain function or evidence of brain pathology caused by external physical forces. Globally, TBI affects approximately 50 million individuals annually, with nearly half of the population experiencing it at some point in their lives. Severe TBI is associated with a high mortality rate (30–40%) and long-term physical, psychological, and social impairments in up to 60% of cases. TBI ranges from scalp injuries to severe intracerebral damage, with severity assessed by injury severity scores and consciousness levels (Glasgow coma scale). Diffuse axonal injuries (DAI) cause minimal anatomical damage with severe loss of consciousness, affecting treatment and prognosis.Current Concepts: TBI treatment focuses on hemostasis and intracranial pressure (ICP) management to achieve the main goal of preventing secondary brain injury. Early avoidance of hypotension and hypoxia is crucial. Recent advancements include: first, multimodal brain monitoring by utilizing invasive and non-invasive ICP methods, brain oxygenation measurement, and cerebral blood flow assessments for early detection and treatment guidance; second, using biomarkers for TBI (such as GFAP, S100B, NSE, NFL, UCH-L1, and IL-1β) for diagnosis and prognosis prediction; third, target temperature management in which hypothermia therapy reduces ICP and controls inflammation; and fourth, investigating novel pharmacological therapeutics like corticosteroids, progesterone, erythropoietin, amantadine, and anticonvulsants, although several large-scale trials have revealed a lack of significant benefits.Discussion and Conclusion: TBI remains a leading cause of mortality with unresolved challenges. Research has focused on optimizing neuro-intensive care protocols, developing evidence-based surgical treatments, and exploring promising neuroprotective pharmacotherapies. Given TBI’s pathological heterogeneity, personalized medicine and combination therapies are crucial, as no single treatment addresses all mechanisms. Advancements in monitoring technologies and biomarker development are expected to significantly enhance diagnosis, prognosis prediction, and tailored treatment strategies.

Unveiling Interactions between Self-Assembling Peptides and Neuronal Membranes.

The use of self-assembling peptide hydrogels in the treatment of spinal cord and brain injuries, especially when combined with adult neural stem cells, has shown great potential. To advance tissue engineering, it is essential to understand the effect of mechanochemical signaling on cellular differentiation. The elucidation of the molecular interactions at the level of the neuronal membrane still represents a promising area of investigation for many drug delivery and tissue engineering applications. An innovative molecular dynamics framework has been introduced to investigate the effect of SAP fibrils with different charges on neural membrane lipid domain dynamics. Such advance enables the in silico exploration of the biomimetic properties of SAP hydrogels and other polymeric biomaterials for tissue engineering applications.

Astrocyte–neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury

Although astrocytes undergo functional changes in response to brain injury and may be the driving force of subsequent neuronal death, the underlying mechanisms remain incompletely elucidated. Here, we showed that extracellular vesicle (EV)-shuttled miRNA-382-5p may serve as a biomarker for the severity of traumatic brain injury (TBI), as the circulating EV-miRNA-382-5p level was significantly increased in both human patients and TBI model mice. Mechanistically, astrocyte-derived EVs delivered the shuttled miRNA-382-5p to mediate astrocyte–neuron communication, which promoted neuronal mitochondrial dysfunction by inhibiting the expression of optic atrophy-1 (OPA1). Consistent with these findings, genetic ablation of neuronal OPA1 exacerbated mitochondrial damage and neuronal apoptosis in response to TBI. Moreover, engineered RVG-miRNA-382-5p inhibitor-EVs, which can selectively deliver a miRNA-382-5p inhibitor to neurons, significantly attenuated mitochondrial damage and improved neurological function after TBI. Taken together, our data suggest that EV-shuttled miRNA-382-5p may be a critical mediator of astrocyte-induced neurotoxicity under pathological conditions and that targeting miRNA-382-5p-OPA1 signaling has potential for clinical translation in the treatment of traumatic brain injury.

Tibetan golden acupuncture inhibits JNK/caspase-3 signaling pathway to alleviate neuronal apoptosis in cerebral ischemia-reperfusion injury

Tibetan golden acupuncture inhibits JNK/caspase-3 signaling pathway to alleviate neuronal apoptosis in cerebral ischemia-reperfusion injury

Neuroprotective Effects of Ethanol Extract Polyscias guilfoylei (EEPG) Against Glutamate Induced Neurotoxicity in HT22 Cells.

Oxidative stress induced by glutamate is a significant contributor to neuronal cell damage and can lead to neurodegenerative diseases such as Alzheimer's, Huntington's, and ischemic brain injury. At the cellular level, oxidative stress increases Ca2+ ion influx and reactive oxygen species (ROS), which activate the MAPK signaling pathway. Additionally, the generation of ROS causes mitochondrial dysfunction, triggering apoptosis by promoting the translocation of AIF to the nucleus from the mitochondria. The neuroprotective potential of Polyscias guilfoylei has not yet been reported. Therefore, in this study, the ethanol extract of Polyscias guilfoylei (EEPG) was examined for its protective effect against oxidative cell damage caused by glutamate in neuronal cells. EEPG treatment increased the viability of HT22 cells exposed to high concentrations of glutamate. Cellular Ca2+ ion influx and ROS generation decreased with EEPG treatment in glutamate-treated HT22 cells. EEPG treatment inhibited MAPK activation and AIF nuclear translocation. In an in vivo study, EEPG attenuated brain cell death in an ischemic brain injury rat model. This study demonstrates the potential therapeutic effects of Polyscias guilfoylei in the treatment of ischemic brain injury.

Design and methodology of a randomized clinical trial of quetiapine to reduce central nervous system polypharmacy in veterans with postconcussive syndrome symptoms

Lack of evidence to guide medication treatments for mild traumatic brain injury (mTBI) in veterans too often results in polypharmacy practices attempting to provide symptomatic relief from multiple postconcussive syndrome symptoms. Therefore, the field needs to find an effective medication that reduces the burden of postconcussive symptoms without complicating the treatment burden of veterans. This clinical trial seeks to determine whether switching veterans to quetiapine monotherapy (intervention) is superior to continuing to receive treatment as usual (TAU, control) polypharmacy for veterans with symptoms of postconcussive syndrome and posttraumatic stress disorder who are receiving rehabilitation treatment for mTBI. This study will test the conceptual mediation model hypothesis that quetiapine monotherapy may enhance recovery from mTBI by (1) increasing engagement in rehabilitation services, and/or (2) reducing the adverse effects of TAU polypharmacy. This study will enroll 146 patients from two Veterans Administration Medical Centers into a 12- week phase III, randomized, pragmatic clinical trial comparing outcomes from treatment with quetiapine monotherapy and TAU. Quetiapine will be cross tapered up to a maximum dose of 200mg (as tolerated) as other medications are discontinued. The primary outcome measures are postconcussive syndrome symptoms (Neurobehavioral Symptom Inventory), functional disability (World Health Organization Disability Assessment), and quality of life (World Health Organization Quality of Life Assessment). Overall, this study aims to determine whether quetiapine monotherapy is superior to TAU polypharmacy and improves the quality of life for veterans with comorbid postconcussive syndrome and posttraumatic stress disorder symptoms who are receiving rehabilitation treatment for mTBI.

Systematic quantitative evaluation of gene polymorphism and therapeutic effect of xingnaojing injection in patients with brain injury.

The incidence of brain injury is increasing year by year, and it has become one of the major diseases threatening human life in today's society. From the perspective of the causes of brain injury, it is mainly due to falls from high places, traffic accidents, etc. Severe brain injury patients often lose consciousness. In recent years, the emergence of integrated traditional Chinese and Western medicine has provided a new approach and new ideas for the treatment of craniocerebral trauma. The article systematically and scientifically expounded the role of Xingnaojing injection in the treatment of brain injury by comparing the GCS (Glasgow Coma Scale) score, changes in intracranial pressure, the incidence of complications after brain injury, the transformation from moderate brain injury to severe brain injury, and recovery of consciousness. For the problem of gene polymorphism in patients with brain injury, this article discussed the role of APOE2 (Apolipoprotein E2), ε3, ε4 in brain injury. All patients had a clear history of trauma and received strict nervous system examination and CT scanning when they were admitted to the hospital. After craniocerebral trauma surgery or conservative therapy, patients should take a Xingnaojing injection of 30 ml and a 0.9% sodium chloride injection of 250 ml after admission. After the operation, respiratory tract nursing should be strengthened, and patients who cannot eat should be given nasal feeding, acupuncture, and physiotherapy to prevent bedridden complications. The probability of epilepsy after brain injury was 27%. The article would help to evaluate the degree of brain damage and prognosis of patients.

Antisecretory Factor 16 (AF16): A Promising Avenue for the Treatment of Traumatic Brain Injury—An In Vitro Model Approach

Traumatic brain injury (TBI) is caused by an external mechanical force to the head, resulting in abnormal brain functioning and clinical manifestations. Antisecretory factor (AF16) is a potential therapeutic agent for TBI treatment due to its ability to inhibit fluid secretion and decrease inflammation, intracranial pressure, and interstitial fluid build-up, key hallmarks presented in TBI. Here, we investigated the effect of AF16 in an in vitro model of neuronal injury, as well as its impact on key components of the autophagy pathway and mitochondrial dynamics. N2Awt cells were treated with AF16, injured using a scratch assay, and analysed using confocal microscopy, correlative light and electron microscopy (CLEM), flow cytometry, and western blotting. Our results reveal that AF16 enhances autophagy activity, regulates mitochondrial dynamics, and provides protection as early as 6 h post-injury. Fluorescently labelled AF16 was observed to localise to lysosomes and the autophagy compartment, suggesting a role for autophagy and mitochondrial quality control in conferring AF16-associated neuronal protection. This study concludes that AF16 has potential as a therapeutic agent for TBI treatment through is regulation of autophagy and mitochondrial dynamics.

Comorbid treatment of traumatic brain injury and mental health disorders.

The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders. This article reviews the EHVP. The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans. This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all. Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.

Dynamic Craniotomy With Khanna NuCrani Plates as an Alternative to Craniotomy With Fixed Plates in Traumatic Brain Injury.

Dynamic craniotomy as opposed to a fixed plate craniotomy provides cranial decompression with a controlled outward bone flap movement to accommodate postoperative cerebral swelling and/or hemorrhage. The objective of this study was to evaluate if fixation of the bone flap following a trauma craniotomy with dynamic plates provides any advantage over fixed plates. A review of our clinical series of 25 consecutive adult patients undergoing dynamic craniotomy with the Khanna NuCrani reversibly expandable bone flap fixation plates for the treatment of traumatic brain injury associated with mass lesions including subdural, epidural, and cerebral hematomas was conducted. Postoperative cerebral swelling was encountered in 21 of 25 patients (84%), which was compensated for with outward bone flap movement in all these patients and associated decreased midline shift. Severe brain swelling with outward bone flap movement of 8 mm or more was noted in 40% of the patients. All patients had a normal intracranial pressure after surgery. None of the patients required any reoperations for hematoma evacuation, rescue decompressive craniectomies, cranioplasty, or complications related to wound healing. The bone flap retracted after the resolution of the brain swelling, and none of the patients reported cosmetic symptoms related to bone flap or wound healing. Overall, 84% (21 of 25) of the patients achieved a good outcome. Craniotomy bone flap fixation with dynamic plates is an alternative to craniotomy with fixed plates. The main advantage of dynamic craniotomy over a craniotomy with fixed plates is that it allows for immediate intracranial volume expansion with reversible outward bone flap migration in patients who may develop postoperative worsening brain swelling and/or hemorrhage, with decreased need for repeat surgeries and associated complications.