Papers by Brandon Lucke-wold
Advances in translational medicine, Mar 11, 2024
Astrocytes are cells in the central nervous system (CNS) that are responsible for many things, su... more Astrocytes are cells in the central nervous system (CNS) that are responsible for many things, such as maintaining blood brain barrier (BBB), regulating synapses in the spinal cord, and responding to spinal cord injury (SCI). Astrogliosis, the astrocytic response to spinal cord injuries (SCIs), helps repair CNS damages by regulating different protein filaments, thus limiting axonal growth. Former studies that were demonstrated through laser capture microdissection and immunohistochemistry (IHC) helped to identify important genes involved in experimental therapies for SCIs. Additionally, there are potential clinical treatments options for SCIs such as hydrogels, mesenchymal stem cells and steroids. Increased imaging modalities indicate that excessive astrogliosis can have adverse effects. These imaging techniques include positron emission tomography (PET), magnetic resonance imaging (MRI), and two-photon laser-scanning microscopy (TPLSM). These techniques illuminate greater details of the astrocytic response to SCIs. Despite these findings, astrogliosis is not well understood by the research community. Many of the studies presented in this literature review are experimental attempts to understand the mechanisms of astrogliosis in SCIs. This literature review aims to summarize the methods of each study in visualizing the mechanisms of astrogliosis and how they play a role in SCIs. Furthermore, this paper is aimed to comprehensively bridge the developments in the treatment for SCI patients based on innovative imaging modalities. Compared to prior studies, this review utilizes more recent understandings of the astrogliosis mechanisms to highlight insights into targeted developments, both clinically and preclinically. Some limitations of this literature review include the limited studies on astrogliosis and its impact on SCIs. Nonetheless, there is ongoing potential in the search for treatments for SCIs.
Medical sciences, Jan 25, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited v... more Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments for cerebral tumors. It will focus on the current and, more importantly, developing hemangioblastoma treatments. Surgical resectioning and radiotherapy are effective treatment options for cerebral tumors, whereas chemotherapies are not commonly used due to their limited ability to penetrate the blood-brain barrier. Recent chemotherapies have shown promise, but further research is needed to determine the efficacy as a treatment for hemangioblastomas. New advances in brachytherapy and immunotherapy are considered promising treatment options for hemangioblastoma. This review aims to offer valuable insights into the latest developments in hemangioblastoma treatments.
Academia Biology, Dec 10, 2023
Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of... more Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of morbidity and mortality. Posthemorrhage cerebral vasospasm (PHCV) occurs through a complex pathophysiology, and numerous pharmacologic agents, including vasodilators, anti-inflammatories, and fibrinolytics, as well as endovascular techniques have been used to prevent and/or treat PHCV. Nimodipine continues to be the only agent with level 1 evidence, but other vasodilators have demonstrated promising results. Endovascular therapy likely has a role in treating severe/refractory PHCV, but randomized trials are needed to establish stronger evidence for this therapy. Numerous preclinical investigations highlight novel targets related to the immune response that could prove effective at improving outcomes in clinical trials. Further investigation of the glymphatic system and its role in PHCV pathogenesis could result in novel pharmacologic targets. Future trials of these therapies and combinations of existing therapies are needed, and functional outcomes should be included as an endpoint. Further exploration of the neuroinflammatory reaction following aSAH will continue to identify targetable molecules involved in PHCV pathogenesis.
As the average lifespan has increased, memory disorders have become a more pressing public health... more As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient's risk for and experience of dementia.
Journal of Cellular Immunology, Sep 27, 2023
Stroke is a debilitating neurologic condition characterized by an interruption or complete blocka... more Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke. Of these secondary mechanisms of injury, significant dysregulation of various immune populations within the body plays a crucial role in exacerbating brain damage after stroke. Pathological activity of glial cells, infiltrating leukocytes, and the adaptive immune system promote neuroinflammation, BBB damage, and neuronal death. Chronic immune activation can additionally encourage the development of neurologic deficits, immunosuppression, and dysregulation of the gut microbiome. As such, immunotherapy has emerged as a promising strategy for the clinical management of stroke in a highly patient-specific manner. These strategies include regulatory T cells (Tregs), cell adhesion molecules, cytokines, and monoclonal antibodies. However, the use of immunotherapy for stroke remains largely in the early stages, highlighting the need for continued research efforts before widespread clinical use.
Biomedicines
Clinicians have managed and treated lower back pain since the earliest days of practice. Historic... more Clinicians have managed and treated lower back pain since the earliest days of practice. Historically, lower back pain and its accompanying symptoms of radiating leg pain and muscle weakness have been recognized to be due to any of the various lumbar spine pathologies that lead to the compression of the lumbar nerves at the root, the most common of which is the radiculopathy known as sciatica. More recently, however, with the increased rise in chronic diseases, the importance of differentially diagnosing a similarly presenting pathology, known as lumbosacral plexopathy, cannot be understated. Given the similar clinical presentation of lumbar spine pathologies and lumbosacral plexopathies, it can be difficult to differentiate these two diagnoses in the clinical setting. Resultingly, the inappropriate diagnosis of either pathology can result in ineffective clinical management. Thus, this review aims to aid in the clinical differentiation between lumbar spine pathology and lumbosacral ...
Biomedicines
The present review aimed to identify the means through which neurologic injury can predispose ind... more The present review aimed to identify the means through which neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system can lead to distinct PTSD symptoms—namely, dissociative reactions or flashbacks—when damaged. Our review narrowed its focus to three common neurologic injuries, traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. We found that in each of the three cases, individuals may be at an increased risk of developing PTSD symptoms. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the effect of noradrenergic neuromodulatory signaling on the hypothalamic pituitary adrenal (HPA) axis as it pertains to fear memory recall needs ...
Biomedicines, Oct 21, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Medicina
Augmented reality (AR) involves the overlay of computer-generated images onto the user’s real-wor... more Augmented reality (AR) involves the overlay of computer-generated images onto the user’s real-world visual field to modify or enhance the user’s visual experience. With respect to neurosurgery, AR integrates preoperative and intraoperative imaging data to create an enriched surgical experience that has been shown to improve surgical planning, refine neuronavigation, and reduce operation time. In addition, AR has the potential to serve as a valuable training tool for neurosurgeons in a way that minimizes patient risk while facilitating comprehensive training opportunities. The increased use of AR in neurosurgery over the past decade has led to innovative research endeavors aiming to develop novel, more efficient AR systems while also improving and refining present ones. In this review, we provide a concise overview of AR, detail current and emerging uses of AR in neurosurgery and neurosurgical training, discuss the limitations of AR, and provide future research directions. Following ...
Journal of Modern Medical Oncology
Management of central nervous system lymphoma requires multidisciplinary care. The disease can ma... more Management of central nervous system lymphoma requires multidisciplinary care. The disease can manifest in the context of immunocompromised states or in the context of chronic infections. Nervous system damage from this lymphoma has highly variable presentation that is dependent on the location of the tumor lesions. Damage from disease progression can lead to lasting neurologic deficits and even death. However, some lesions are a consequence of radiation-induced neurotoxicity. This review discusses the sources of and consequences of brain damage due to tumor damage and the associated effect of clinical therapies. We discuss workup, management, and treatments. These include chemotherapy and radiation techniques. We discuss potential complications and avoidance strategies. The review will serve as a user-friendly resource for clinicians.
Clinical Research Communications
Allergic reactions in neurosurgical procedures are uncommon, but they are detrimental to a patien... more Allergic reactions in neurosurgical procedures are uncommon, but they are detrimental to a patient's prognosis and recovery. By synthesizing data collected from other surgical fields, possible triggers and alternatives have been identified. Current treatment guidelines involve stabilizing the patient in emergency situations, symptom management, and identification of causative allergens. Preoperative allergy screening is uncommon due to the low prevalence of perioperative hypersensitivity reactions. However, preoperative questionnaire screening can identify when preoperative allergy screening, premedication, or use of a material alternative is necessary. Greater emphasis on material alternatives, increased preoperative screening, and more data can improve the prognosis of neurosurgical patients at risk of perioperative allergic complications.
Current Oncology
The assessment and treatment of vertebral primary bone lesions continue to pose a unique yet sign... more The assessment and treatment of vertebral primary bone lesions continue to pose a unique yet significant challenge. Indeed, there exists little in the literature in the way of compiling and overviewing the various types of vertebral lesions, which can often have complicated intervention strategies. Given the severe consequences of mismanaged vertebral bone tumors—including the extreme loss of motor function—it is clear that such an overview of spinal lesion care is needed. Thus, in the following paper, we aim to address the assessment of various vertebral primary bone lesions, outlining the relevant nonsurgical and surgical interventional methods. We describe examples of primary benign and malignant tumors, comparing and contrasting their differences. We also highlight emerging treatments and approaches for these tumors, like cryoablation and stereotactic body radiation therapy. Ultimately, we aim to emphasize the need for further guidelines in regard to correlating lesion type with...
Biomedical Science and Clinical Research, 2022
Neurologic injury often influences various bodily functions associated with digestion. It is impe... more Neurologic injury often influences various bodily functions associated with digestion. It is imperative for an individual to obtain proper nutrients to maintain a healthy lifestyle and recover from injury. In this review, we explore variables and methods of enteral tube placement in neurologic injury patients influencing recovery, specifically G-and J-tubes. We will first review the patient population by identifying leading causes for enteral tube placement among both pediatric and adult neurologic patients. We will then discuss the general procedures for placement and safety considerations for specified patient populations. We will explore interventions limiting placement of the G-and J-tubes by focusing on two interventions: ventriculoperitoneal shunt (VPS) and intrathecal baclofen (ITB). Then, we will highlight nutritional enhancers that may influence general treatment. Finally, we discuss proper weaning procedures and effective methods fitting patient needs.
Journal of Neurology and Psychology, 2018
Concussion in athletes can contribute to early neuropsychological changes that may be indicative ... more Concussion in athletes can contribute to early neuropsychological changes that may be indicative of future neurodegenerative disease. One of the hallmark findings of chronic traumatic encephalopathy is anxiety and impulsive behavior that often develops early in the course of the disease. The behavioral dysfunction can be grouped into a broader category referred to as cognitive disruption. The current gold standard for diagnosing chronic neurodegeneration is post-mortem evaluation of tauopathy to identify neurofibrillary tau tangles in neurons. Few studies, however, have looked at clinical correlations between acute injury and chronic neurodegeneration in terms of behavior. This lack of focus towards translational study has limited advancements towards treatment. In this pilot investigation, the acute cognitive and emotional (anger, impulsivity, and anxiety) affects of concussion in a cohort of collegiate athletes (n = 30) are examined and compared to findings in the post-mortem pathologic features of chronic traumatic encephalopathy. Specifically, the role of the seroternergic system with alpha synuclein and tauopathy staining and the potential for early clinically relevant behavioral and pharmaceutical interventions was investigated. The purpose was to determine if athletes began demonstrating cognitive disruption present in post-mortem evaluation during the acute phase of injury. The acute data was collected via questionnaires within ten days of the athletes' concussion diagnosis. Results demonstrated that 11 of 30 athletes (36%) scored in a diagnosable range of anxiety post-concussion, and athletes scored above the norm in state-anger (M = 22.9, SD = 9.99), indicating severe emotional disturbance. A limitation is that due to the long time frame from acute injury to the development of neurodegeneration individual athletes cannot be tracked in longevity thus limiting the findings to the realm of correlation. The findings from this pilot study warrant further investigation into the neuropsychological aspects for how to manage concussion and prevent degenerative disease.
Biomedical Research and Clinical Practice
Lymphoma presenting as a scalp mass is a rare but serious medical condition mandating aggressive ... more Lymphoma presenting as a scalp mass is a rare but serious medical condition mandating aggressive treatment and neurosurgical intervention. We report a case of 53-year-old male who presented with a large right sided frontal scalp mass and a smaller mass located on the left frontal scalp. After discussion with the patient, it was decided to resect the larger mass for definitive diagnosis. After subtotal resection of the mass, biopsy revealed WHO grade 1 follicular lymphoma (FL), diffuse pattern stage IV. The patient was subsequently treated with 4 grays (Gy) of palliative radiotherapy over 2 fractions to the right frontal scalp and systemic chemo-immunotherapy (6 cycles) followed by rituximab maintenance. Lumbar puncture to obtain cerebrospinal fluid was done a month after therapy began and the results were negative for spread of malignant cells. Approximately 3 months after initiation of therapy, PET/CT showed no evidence of active malignancy and MRI revealed a complete internal resolution of the enlarged right frontal scalp mass. We use this case to provide a detailed discussion regarding disease pathophysiology, early diagnosis, and management Keywords scalp mass; follicular lymphoma; radiotherapy; chemo-immunotherapy This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
J
The glymphatic system is a newly discovered waste-clearing system that is analogous to the lympha... more The glymphatic system is a newly discovered waste-clearing system that is analogous to the lymphatic system in our central nervous system. Furthermore, disruption in the glymphatic system has also been associated with many neurodegenerative disorders (e.g., Alzheimer’s disease), traumatic brain injury, and subarachnoid hemorrhage. Thus, understanding the function and structure of this system can play a key role in researching the progression and prognoses of these diseases. In this review article, we discuss the current ways to map the glymphatic system and address the advances being made in preclinical mapping. As mentioned, the concept of the glymphatic system is relatively new, and thus, more research needs to be conducted in order to therapeutically intervene via this system.
Diseases
Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often re... more Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often results in a loss of many productive years. SAH has a high mortality rate, and survivors often suffer from early and secondary brain injuries. Understanding the pathophysiology of the SAH is crucial in identifying potential therapeutic agents. One promising target for the diagnosis and prognosis of SAH is circulating microRNAs, which regulate gene expression and are involved in various physiological and pathological processes. In this review, we discuss the potential of microRNAs as a target for diagnosis, treatment, and prognosis in SAH.
European Neurology
Background: Ferritin is a protein that is critical for storing iron. Ferritin has recently been s... more Background: Ferritin is a protein that is critical for storing iron. Ferritin has recently been shown to play a role in iron homeostasis, immunomodulation, inflammation, and antioxidation. Previously, it was believed that ferritin was exclusively an intracellular peptide. However, there is significant evidence that ferritin is also in the serum, cerebral spinal fluid, and synovial fluid. Summary: Within the brain, ferritin can bind to oligodendrocytes adjacent to the blood-brain barrier to allow a docking point for ferritin to be engulfed by microglia in the brain parenchyma. When iron supplies in the brain are low, the lysosomal-autophagy pathway is activated to degrade ferritin and mobilize iron. Iron is critical in the brain for the formation of myelin and used during cellular respiration. If this sequestration and degradation of iron are impaired, the oxidative effects of iron may leave the brain vulnerable to neurotoxic effects. Subarachnoid hemorrhage (SAH) causes hemolysis of...
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Papers by Brandon Lucke-wold