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Item 7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection(Elsevier, 2022) Lin, Xiaojing; Zhao, Tingbao; Mei, Guiping; Liu, Ruoxu; Li, Chenyi; Wang, Xiaowen; Qu, Zixuan; Lin, Shide; Walker, M. J.; Yi, Xueqing; Zhang, Peng; Tseng, Kuang-Wen; Xu, Xiao-Ming; Lin, Cheng-Hsien; Sun, Gang; Neurological Surgery, School of MedicineBackground: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. Methods: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. Results: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. Conclusions: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.Item A Contemporary Clinico-Anatomical Guide to Craniovertebral Junction Surgery(Thieme, 2022-09-28) Spiessberger, Alexander; Gruter, Basil; Prashant, Giyarpuram; Haegler, Joshua; Eisenberg, Mark; Cohen-Gadol, Aaron A.; Dehdashti, Amir R.; Neurological Surgery, School of MedicineBackground: Surgical treatment of ventral and ventrolateral lesions of the craniocervical junction are among the most challenging neurosurgical pathologies to treat. Three surgical techniques, the far lateral approach (and its variations), the anterolateral approach, and the endoscopic far medial approach can be used to approach and resect lesions in this area. Objective: The aim of the study is to examine the surgical anatomy of three skull base approaches to the craniocervical junction and review surgical cases to better understand the indications and possible complications for each of these approaches. Methods: Cadaveric dissections with standard microsurgical and endoscopic instruments were performed for each of the three surgical approaches, and key steps and surgically relevant anatomy were documented. Six patients with appropriate pre-, post-, and intraoperative imaging and video documentation are presented and discussed accordingly. Results: Based on our institutional experience, all three approaches can be utilized to safely and effectively approach a wide variety of neoplastic and vascular pathology. Unique anatomical characteristics, lesion morphology and size, and tumor biology should all be considered when determining the optimal approach. Conclusion: Preoperative assessment of surgical corridors with 3D illustrations helps to define the best surgical corridor. 360 degree knowledge of the anatomy of craniovertebral junction allows safe surgical approach and treatment of ventral and ventrolateral located lesions using one of the three approaches.Item A Retrospective Review of 30-Day Hospital Readmission Risk After Open Heart Surgery in Patients With Atrial Fibrillation(Springer Nature, 2023-09-22) Rao, Varun; DeLeon, Genaro; Thamba, Aish; Flanagan, Mindy; Nickel, Kathleen; Gerue, Michael; Gray, Douglas; Neurological Surgery, School of MedicineIntroduction: Readmission rates after open heart surgery (OHS) remain an important clinical issue. The causes are varied, with identifying risk factors potentially providing valuable information to reduce healthcare costs and the rate of post-operative complications. This study aimed to characterize the reasons for 30-day hospital readmission rates of patients after open heart surgery. Methods: All patients over 18 years of age undergoing OHS at a community hospital from January 2020 through December 2020 were identified. Demographic data, medical history, operative reports, post-operative complications, and telehealth interventions were obtained through chart review. Descriptive statistics and readmission rates were calculated, along with a logistic regression model, to understand the effects of medical history on readmission. Results: A total of 357 OHS patients met the inclusion criteria for the study. Within the population, 8.68% of patients experienced readmission, 10.08% had an emergency department (ED) visit, and 95.80% had an outpatient office visit. A history of atrial fibrillation (AFib) significantly predicted 30-day hospital readmissions but not ED or outpatient office visits. Telehealth education was delivered to 66.11% of patients. Conclusion: The study investigated factors associated with 30-day readmission following OHS. AFib patients were more likely to be readmitted than patients without atrial fibrillation. No other predictors of readmission, ED visits, or outpatient office visits were found. Patients reporting symptoms of tachycardia, pain, dyspnea, or "other" could be at increased risk for readmission.Item A Sodium Oxychlorosene-Based Infection Prevention Protocol Safely Decreases Postoperative Wound Infections in Adult Spinal Deformity Surgery(Springer Nature, 2024-03-13) Alentado, Vincent J.; Kazi, Fezaan A.; Potts, Caroline A.; Zaazoue, Mohamed A.; Pott, Eric A.; Khairi, Saad A.; Neurological Surgery, School of MedicineIntroduction: This study sought to determine the efficacy of a complex multi-institutional sodium oxychlorosene-based infection protocol for decreasing the rate of surgical site infection after instrumented spinal surgery for adult spinal deformity (ASD). Infection prevention protocols have not been previously studied in ASD patients. Methods: A retrospective analysis was performed of patients who underwent posterior instrumented spinal fusion of the thoracic or lumbar spine for deformity correction between January 1, 2011, and May 31, 2019. The efficacy of a multi-modal infection prevention protocol was examined. The infection prevention bundle consisted of methicillin-resistant Staphylococcus aureus testing, chlorhexidine gluconate bathing preoperatively, sodium oxychlorosene rinse, vancomycin powder placement, and surgical drain placement at the time of surgery. Results: About 254 patients fit the inclusion criteria. Among these patients, nine (3.5%) experienced post-surgical deep-wound infection. Demographics and surgical characteristics amongst infected and non-infected cohorts were similar, although diabetes trended towards being more prevalent in patients who developed a postoperative wound infection (p=0.07). Among 222 patients (87.4%) who achieved a minimum of two years of follow-ups, 184 patients (82.9%) experienced successful fusion, comparing favorably with pseudarthrosis rates in the ASD literature. Rates of pseudarthrosis and proximal junction kyphosis were similar amongst infected and non-infected patients. Conclusion: An intraoperative comprehensive sodium oxychlorosene-based infection prevention protocol helped to provide a low rate of infection after major deformity correction without negatively impacting other postoperative procedure-related metrics.Item AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury(hindawi publishing corporation, 2017) Li, Wen-Yuan; Wang, Ying; Zhai, Feng-Guo; Sun, Ping; Cheng, Yong-Xia; Deng, Ling-Xiao; Wang, Zhen-Yu; Neurological Surgery, School of MedicineDPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury.Item Acridine Orange as a Novel Photosensitizer for Photodynamic Therapy in Glioblastoma(Elsevier, 2018) Osman, Hany; Elsahy, Deena; Saadatzadeh, M. Reza; Pollok, Karen E.; Yocom, Steven; Hattab, Eyas; Georges, Joseph; Cohen-Gadol, Aaron A.; Neurological Surgery, School of MedicineObject Photodynamic therapy is an exciting treatment modality that combines the effects of a chemical agent with the physical energy from light or radiation to result in lysis of cells of interest. Acridine orange is a molecule with fluorescence properties that was demonstrated to possess photosensitizing properties. The objective of this study was to investigate the photodynamic effect of acridine orange on glioblastoma cell viability and growth. Methods Glioblastoma cells (n = 8000 cells/well at 0 hours) were exposed to acridine orange followed by white unfiltered light-emitting diodes (LED) light. Cultures were exposed to either 10 or 30 minutes of light. The cell number per well was determined at 0, 24, 48, and 72 hours after exposure. Results A dramatic cytocidal effect of acridine orange after exposure to as little as 10 minutes of white light was observed. There was almost complete eradication of the glioblastoma cells over a 72-hour period. Although acridine orange or light alone exhibited some effect on cell growth, it was not as pronounced as the combination of acridine orange and light. Conclusions This is the first study to demonstrate the photodynamic effect of acridine orange in glioblastoma cells. This data supports the need for further studies to characterize and evaluate whether this striking cytotoxic effect can be achieved in vivo. The combination of acridine orange and exposure to white unfiltered LED light may have potential future applications in management of glioblastoma.Item Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies(International Institute of Anticancer Research, 2022-09-03) Bin-Alamer, Othman; Haider, Ali S.; Chaudhary, Adhiraj; Balasubramanian, Kishore; Breeding, Tessa; Palmisciano, Paolo; Haider, Maryam; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Neurological Surgery, School of MedicineBackground/aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.Item Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies(IIAR, 2022-09-03) Bin-Alamer, Othman; Haider, Ali S.; Chaudhary, Adhiraj; Balasubramanian, Kishore; Breeding, Tessa; Palmisciano, Paolo; Haider, Maryam; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Neurological Surgery, School of MedicineBackground/Aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and Methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.Item Aging impairs dendrite morphogenesis of newborn neurons and is rescued by 7, 8-dihydroxyflavone(Wiley Blackwell (Blackwell Publishing), 2017-04) Wang, Xiaoting; Romine, Jennifer Lynn; Gao, Xiang; Chen, Jinhui; Neurological Surgery, School of MedicineAll aging individuals will develop some degree of decline in cognitive capacity as time progresses. The molecular and cellular mechanisms leading to age-related cognitive decline are still not fully understood. Through our previous research, we discovered that active neural progenitor cells selectively become more quiescent in response to aging, thus leading to the decline of neurogenesis in the aged hippocampus. Here, we further find that aging impaired dendrite development of newborn neurons. Currently, no effective approach is available to increase neurogenesis or promote dendrite development of newborn neurons in the aging brain. We found that systemically administration of 7, 8-dihydroxyflavone (DHF), a small molecule imitating brain-derived neurotrophic factor (BDNF), significantly enhanced dendrite length in the newborn neurons, while it did not promote survival of immature neurons, in the hippocampus of 12-month-old mice. DHF-promoted dendrite development of newborn neurons in the hippocampus may enhance their function in the aging animal leading to a possible improvement in cognition.Item Aging- and Tumor-Mediated Increase in CD8+CD28- T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma(American Association of Immunologists, 2021-06-08) Huff, Wei X.; Bam, Marpe; Shireman, Jack M.; Kwon, Jae Hyun; Song, Leo; Newman, Sharlé; Cohen-Gadol, Aaron A.; Shapiro, Scott; Jones, Tamara; Fulton, Kelsey; Liu, Sheng; Tanaka, Hiromi; Liu, Yunlong; Wan, Jun; Dey, Mahua; Neurological Surgery, School of MedicineClinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T-cell dysfunction such as exhaustion in GBM patients. However, reversing T-cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 co-receptors, low CD27 expression, increased CD57 expression, and telomere shortening, are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T-cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in antigen induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28− T-cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T-cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28− T-cells in both the blood and tumor infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28− T-cells represent a distinct population compared to exhausted T-cells. Comparative transcriptomic and pathway analysis of CD8+CD28− T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.