Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease and the world's primary cause of dementia, a condition characterized by significant progressive declines in memory and intellectual capacities. While dementia is the main symptom of Alzheimer's, the disease presents with many other debilitating symptoms, and currently, there is no known treatment exists to stop its irreversible progression or cure the disease. Photobiomodulation has emerged as a very promising treatment for improving brain function, using light in the range from red to the near-infrared spectrum depending on the application, tissue penetration, and density of the target area. The goal of this comprehensive review is to discuss the most recent achievements in and mechanisms of AD pathogenesis with respect to neurodegeneration. It also provides an overview of the mechanisms of photobiomodulation associated with AD pathology and the benefits of transcranial near-infrared light treatment as a potential therapeutic solution. This review also discusses the older reports and hypotheses associated with the development of AD, as well as some other approved AD drugs.

Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.

Cholangiocyte proliferation is regulated in a coordinated fashion by many neuroendocrine factors through autocrine and paracrine mechanisms. The renin-angiotensin system (RAS) is known to play a role in the activation of hepatic stellate cells and blocking the RAS attenuates hepatic fibrosis. We investigated the role of the RAS during extrahepatic cholestasis induced by bile duct ligation (BDL). In this study, we used normal and BDL rats that were treated with control, angiotensin II (ANG II), or losartan for 2 wk. In vitro studies were performed in a primary rat cholangiocyte cell line (NRIC). The expression of renin, angiotensin-converting enzyme, angiotensinogen, and angiotensin receptor type 1 was evaluated by immunohistochemistry (IHC), real-time PCR, and FACs and found to be increased in BDL compared with normal rat. The levels of ANG II were evaluated by ELISA and found to be increased in serum and conditioned media of cholangiocytes from BDL compared with normal rats. Treatment with ANG II increased biliary mass and proliferation in both normal and BDL rats. Losartan attenuated BDL-induced biliary proliferation. In vitro, ANG II stimulated NRIC proliferation via increased intracellular cAMP levels and activation of the PKA/ERK/CREB intracellular signaling pathway. ANG II stimulated a significant increase in Sirius red staining and IHC for fibronectin that was blocked by angiotensin receptor blockade. In vitro, ANG II stimulated the gene expression of collagen 1A1, fibronectin 1, and IL-6. These results indicate that cholangiocytes express a local RAS and that ANG II plays an important role in regulating biliary proliferation and fibrosis during extraheptic cholestasis.

Astrocytic calcium waves: unveiling their roles in sleep and arousal modulation.

Neuron-astrocyte interactions are vital for the brain's connectome. Understanding astrocyte activities is crucial for comprehending the complex neural network, particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals. Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons. Astrocytes, outnumbering neurons by nearly fivefold, support and regulate neuronal and synaptic function. Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling. This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep, wakefulness, and arousal levels, exploring the involvement of noradrenaline signaling, ion channels, and glutamatergic signaling in different cortical states. These findings highlight the significant impact of astrocytes on large-scale neuronal networks, influencing brain activity and responsiveness. Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation. More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states, requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep- and arousal-related disorders.

General mechanisms of nicotine-induced fibrogenesis.

Cigarette smoking contributes to the development of cancer, and pathogenesis of other diseases. Many chemicals have been identified in cigarettes that have potent biological properties. Nicotine is especially known for its role in addiction and plays a role in other physiological effects of smoking and tobacco use. Recent studies have provided compelling evidence that, in addition to promoting cancer, nicotine also plays a pathogenic role in systems, such as the lung, kidney, heart, and liver. In many organ systems, nicotine modulates fibrosis by altering the functions of fibroblasts. Understanding the processes modulated by nicotine holds therapeutic potential and may guide future clinical and research decisions. This review discusses the role of nicotine in the general fibrogenic process that governs fibrosis and fibrosis-related diseases, focusing on the cellular mechanisms that have implications in multiple organ systems. Potential research directions for the management of nicotine-induced fibrosis, and potential clinical considerations with regard to nicotine-replacement therapy (NRT) are presented.

Mechanisms of SARS-CoV-2-induced Encephalopathy and Encephalitis in COVID-19 Cases.

The SARS-CoV-2 virus caused an unprecedented pandemic around the globe, infecting 36.5 million people and causing the death of over 1 million in the United States of America alone. COVID-19 patients demonstrated respiratory symptoms, cardiovascular complications, and neurologic symptoms, which in most severe cases included encephalopathy and encephalitis. Hypoxia and the uncontrolled proliferation of cytokines are commonly recognized to cause encephalopathy, while the retrograde trans-synaptic spread of the virus is thought to cause encephalitis in SARS-CoV-2-induced pathogenesis. Although recent research revealed some mechanisms explaining the development of neurologic symptoms, it still remains unclear whether interactions between these mechanisms exist. This review focuses on the discussion and analysis of previously reported hypotheses of SARS-CoV-2-induced encephalopathy and encephalitis and looks into possible overlaps between the pathogenesis of both neurological outcomes of the disease. Promising therapeutic approaches to prevent and treat SARS-CoV-2-induced neurological complications are also covered. More studies are needed to further investigate the dominant mechanism of pathogenesis for developing more effective preventative measures in COVID-19 cases with the neurologic presentation.

Neurogenesis and chronic neurobehavioral outcomes are partially improved by vagus nerve stimulation in a mouse model of Gulf War illness.

Gulf War illness (GWI) is a chronic, multi-symptom disorder that has impacted approximately one third of Gulf War veterans. GWI and its symptoms have been linked to the exposure to neurological chemicals, including the anti-nerve gas drug pyridostigmine bromide (PB) and the insecticide permethrin (PER), among others. Mouse models utilizing these chemicals have reported symptomology analogous to human GWI. These changes include behavioral and cognitive impairment, neuroinflammation and hippocampal pathogenesis. Disease modifying interventions that target these pathological components are desperately needed. Vagus nerve stimulation (VNS) is FDA approved for drug-resistant epilepsy and depression. VNS has also been used off-label to target a myriad of symptoms, some of which are encompassed within the Kansas and CDC definitions of clinical GWI symptomology. A GWI animal model in which mice are exposed to a daily injection of PB and PER for 10 consecutive days has been shown to exhibit cognitive impairment and hippocampal pathology. The purpose of this study was to determine if 2-4 weeks of continuous vagus nerve stimulation initiated at 32 weeks after exposure to PB and PER would improve cognitive performance and hippocampal pathology. The results of the study revealed that exposure to PB and PER produces long-term cognitive deficits and reduced hippocampal neurogenesis. The results also showed that the VNS treatment was anxiolytic, improved some aspects of pattern separation deficits, and mitigated the reduced hippocampal neurogenesis. Thus, VNS improves outcomes in a mouse model of GWI and should be examined as a potential therapeutic strategy for mitigating some symptomology associated with GWI.

Transcranial near-infrared light in treatment of neurodegenerative diseases.

Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy metabolism, and regulation of chronic brain inflammation associated with various conditions, including traumatic brain injury. This scientific overview incorporates the most recent cellular and functional findings in PBM with NIR light in treating neurodegenerative diseases, presents the discussion of the proposed mechanisms of action, and describes the benefits of this treatment in neuroprotection, cell preservation/detoxification, anti-inflammatory properties, and regulation of brain energy metabolism. This review will also discuss the novel aspects and pathophysiological role of the glymphatic and brain lymphatics system in treating neurodegenerative diseases with NIR light stimulations. Scientific evidence presented in this overview will support a combined effort in the scientific community to increase attention to the understudied NIR light area of research as a natural agent in the treatment of neurodegenerative diseases to promote more research and raise awareness of PBM in the treatment of brain disorders.

Antigenic Determinant of Helicobacter pylori FlaA for Developing Serological Diagnostic Methods in Children.

The early diagnosis of Helicobacter pylori infection is important for gastric cancer prevention and treatment. Although endoscopic biopsy is widely used for H. pylori diagnosis, an accurate biopsy cannot be performed until a lesion becomes clear, especially in pediatric patients. Therefore, it is necessary to develop convenient and accurate methods for early diagnosis. FlaA, an essential factor for H. pylori survival, shows high antigenicity and can be used as a diagnostic marker. We attempted to identify effective antigens containing epitopes of high diagnostic value in FlaA. Full-sized FlaA was divided into several fragments and cloned, and its antigenicity was investigated using Western blotting. The FlaA fragment of 1345-1395 bp had strong immunogenicity. ELISA was performed with serum samples from children by using the 1345-1395 bp recombinant antigen fragment. IgG reactivity showed 90.0% sensitivity and 90.5% specificity, and IgM reactivity showed 100% sensitivity and specificity. The FlaA fragment of 1345-1395 bp discovered in the present study has antigenicity and is of high value as a candidate antigen for serological diagnosis. The FlaA 1345-1395 bp epitope can be used as a diagnostic marker for H. pylori infection, thereby controlling various gastric diseases such as gastric cancer and peptic ulcers caused by H. pylori.

Vagus Nerve Stimulation Ameliorates Cognitive Impairment and Increased Hippocampal Astrocytes in a Mouse Model of Gulf War Illness.

Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI symptoms include cognitive impairments (eg, memory and concentration problems), headaches, migraines, fatigue, gastrointestinal and respiratory issues, as well as emotional deficits. The exposure to neurological chemicals such as the anti-nerve gas drug, pyridostigmine bromide (PB), and the insecticide permethrin (PER), may contribute to the etiologically related factors of GWI. Various studies utilizing mouse models of GWI have reported the interplay of these chemical agents in increasing neuroinflammation and cognitive dysfunction. Astrocytes are involved in the secretion of neuroinflammatory cytokines and chemokines in pathological conditions and have been implicated in GWI symptomology. We hypothesized that exposure to PB and PER causes lasting changes to hippocampal astrocytes, concurrent with chronic cognitive deficits that can be reversed by cervical vagus nerve stimulation (VNS). GWI was induced in CD1 mice by injecting the mixture of PER (200 mg/kg) and PB (2 mg/kg), i.p. for 10 consecutive days. VNS stimulators were implanted at 33 weeks after GWI induction. The results show age-related cognitive alterations at approximately 9 months after exposure to PB and PER. The results also showed an increased number of GFAP-labeled astrocytes in the hippocampus and dentate gyrus that was ameliorated by VNS.

Transcranial Near Infrared Light Stimulations Improve Cognition in Patients with Dementia.

Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers' burden with tNIR light treatment of dementia patients.

Gender Differences of Dementia in Response to Intensive Self-Administered Transcranial and Intraocular Near-Infrared Stimulation.

Background Transcranial near-infrared (tNIR) stimulation was proven to be a safe, reliable, and effective treatment for cognitive and behavioral symptoms of dementia. Dementia patients of different genders differ in terms of gross anatomy, biochemistry, genetic profile, clinical presentations, and socio-psychological status. Studies of the tNIR effect on dementia have thus far been gender-neutral, with dementia subjects being grouped based on diagnoses or dementia severity. This trial hereby investigated how dementia subjects of different sex respond to tNIR treatment. Methods A total of 60 patient-caregiver dyads were enrolled and randomized to this double-blind, sham-controlled clinical trial. The tNIR light has a wavelength of 1,060 nm to 1,080 nm and was delivered via a photobiomodulation (PBM) unit. The active PBM unit emits near-infrared (NIR) light while the sham unit does not. The treatment consists of a six-minute tNIR light stimulation session twice daily for eight weeks. Neuropsychological assessments conducted at baseline (week 0) and endline (week 8) were compared within the female and male group and between different sex, respectively. Results Over the course of treatment, active-arm female subjects had a 20.2% improvement in Mini-Mental State Exam (MMSE) (mean 4.8 points increase, p < 0.001) and active-arm male cohort had 19.3% improvement (p < 0.001). Control-arm female subjects had a 6.5% improvement in MMSE (mean 1.5 points increase, p < 0.03) and control-arm male subjects had 5.9% improvement (p = 0.35) with no significant differences in the mean MMSE between female and male subjects in both arms respectively. Other comparison of assessments including Clock Copying and Drawing Test, Logical Memory Test - immediate and delayed recall yielded nominal but not statistically significant differences. No significant differences were observed in the mean MMSE between female and male subjects in both arms respectively before treatment implementation (active arm, p = 0.12; control arm, p = 0.50) at week 0, or after treatment completion (active arm, p = 0.11; control arm, p = 0.74) at week 8. Conclusion Despite differences between female and male dementia subjects, the response to tNIR light stimulation does not demonstrate gender-based differences. Further studies are warranted to refine the tNIR treatment protocol for subjects suffering from dementia or dementia-related symptoms.

Demographics of Astrocytoma in Central Texas: The Interaction Between Race, Histology, and Primary Tumor Site.

Introduction The epidemiological factors surrounding astrocytoma and gliomas have been studied with little avail. Even limited conclusions have not been reached in spite of significant past research efforts. Ionizing radiation is currently one of the only factors consistently associated with glioma formation. Studies in an attempt to link environmental and occupational exposures with brain neoplasms have continued to produce inconsistent results. This study aims to explore the distribution and epidemiology of astrocytomas within a Central Texas patient population in order to elucidate any possible differences in epidemiologic and prognostic factors based on race, histology, and primary tumor site. Methods Eight hundred forty-five clinical cases with the diagnosis of astrocytoma were retrospectively obtained from the tumor registry of the Scott & White Integrated Healthcare System from 1976 to 2014. We investigated the effects of gender, race, tumor histology, tumor site, treatment methods, and mortality of this cohort of patients in Central Texas. Results Prevalence data echoes that of the national epidemiology in that among our sample, White individuals had the highest prevalence (n=666, 78.8%), followed by Hispanics (n=94, 11.1%) and Black individuals (n=78, 9.2%). White patients had higher rates of parietal lobe (6.6% vs. 0.6%, p<0.01), brain overlapping (6.8% vs. 0.0%, p<0.01), and brainstem (5.9% vs. 1.7%, p=0.02) tumors. Black patients had higher rates of tumors located in brain (not otherwise specified) (35.9% vs. 15.7%, p<0.01) and cerebellum (33.3% vs. 5.6%, p<0.01). Hispanic patients had higher rates of tumor located in the temporal lobe (31.9% vs. 22.8%, p<0.05) and brain (not otherwise specified) (28.7% vs. 16.1%, p<0.01). Hispanics had the largest proportion of deaths (72.3% vs. 38.0%, p<0.01) when compared to the remainder of the sample, followed by White individuals (39.6% vs. 49.7%, p=0.02) and Black individuals (21.8% vs. 43.8%, p<0.01). Conclusions Discrepancies in mortality rates amongst various racial groups may be due to a number of factors. Primary tumor site and histology seem to indeed play a role in mortality and may present variably between ethnic groups. Mortality is also influenced by race, genetic predisposition, environmental and occupational exposure, and access to healthcare.

Incidence of Primary Central Nervous System Tumors Among the Hispanic Population in Texas 1995-2013.

INTRODUCTION: Primary central nervous system (CNS) tumors constitute a group of rare and heterogeneous tumors. A rising incidence rate in the United States has been linked to modern changes in early diagnosis and reporting. This study aims to examine temporal incidence trends, geographic variation, and the average annual age-adjusted rates among Hispanic populations in Texas from 1995 to 2013. METHODS: SEER*STAT (Surveillance Research Program, National Cancer Institute (seer.cancer.gov/seerstat) version 8.3.2) and Joinpoint Regression 4.4.0.0 (Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute) software were used to analyze incidence of primary brain and CNS tumors among Texas residents. Data were obtained from the Texas Cancer Registry of the Texas Department of State Health Services. RESULTS: From the 30,122 cases of primary CNS tumors diagnosed throughout the state of Texas from 2008 to 2012, the overall average annual age-adjusted incidence rate for Hispanics and non-Hispanics combined was 25.35 per 100,000 persons. Among Hispanics, West Texas had the highest incidence trends and the highest average age-adjusted incidence rate of 27.17, followed by North Texas at 26.01 and the Panhandle at 23.63. East Texas had the lowest incidence rate of 16.23. The incidence trend among Hispanics has decreased consistently at a rate of 0.83 % from 1995 to 2013. CONCLUSIONS: The incidence of tumors was more pronounced in the Hispanic population in northern Texas compared with southern Texas. The presence of oil and gas production industries with farming and construction could play a role in the observed incidence of disease. Further studies with a focus on occupational health among Hispanics in Texas will be needed to elucidate the cause of such distribution.

Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas from 1995 to 2013.

BACKGROUND: Although rare, primary central nervous system (CNS) tumors are associated with significant morbidity and mortality. Texas is a representative sample of the United States population given its large population, ethnic disparities, geographic variations, and socio-economic differences. This study used Texas data to determine if variations in incidence trends and rates exist among different ethnicities in Texas. METHODS: Data from the Texas Cancer Registry from 1995 to 2013 were examined. Joinpoint Regression Program software was used to obtain the incidence trends and SEER*Stat software was used to produce average annual age-adjusted incidence rates for both nonmalignant and malignant tumors in Texas from 2009 to 2013. RESULTS: The incidence trend of malignant primary CNS tumors in whites was stable from 1995 to 2002, after which the annual percent change decreased by 0.99% through 2013 (95% CI, -1.4, -0.5; P = .04). Blacks and Asian/Pacific Islanders showed unchanged incidence trends from 1995 to 2013. Hispanics had an annual percent change of -0.83 (95% CI, -1.4, -0.2; P = .009) per year from 1995 through 2013. From 2009 to 2013, the incidence rates of nonmalignant and malignant primary CNS tumors were highest among blacks, followed by whites, Hispanics, Asians, and American Indians/Alaskan Natives. CONCLUSIONS: Consistent with the 2016 Central Brain Tumor Registry of the United States report, the black population in Texas showed the highest total incidence of CNS tumors of any other race studied. Many factors have been proposed to account for the observed differences in incidence rate including geography, socioeconomic factors, and poverty factors, although the evidence for these external factors is lacking.

Gulf War agents pyridostigmine bromide and permethrin cause hypersensitive nociception that is restored after vagus nerve stimulation.

Gulf war illness (GWI) is a chronic multi-symptom disease that afflicts 25-33% of troops that were deployed in the 1990-1991 Gulf War. GWI symptoms include cognitive, behavioral and emotional deficits, as well as migraines and pain. It is possible that exposure to Gulf War agents and prophylactics contributed to the reported symptomology. Pyridostigmine bromide (PB) and permethrin (PER) were given to protect from nerve gas attacks and insect vector born disease, respectively. Previous studies have demonstrated that 10 days of exposure to these chemicals can cause symptoms analogous to those observed in GWI, including impairment of long-term memory in mice. Other studies using this model have shown chronic neuroinflammation, and chronic neuroinflammation can lead to altered nociceptive sensitivity. At 10-weeks after the 10-day PB and PER exposure paradigm, we observed lowered nociceptive threshold on the Von Frey test that was no longer evident at 28 weeks and 38 weeks post-exposure. We further determined that vagus nerve stimulation, initiated at 38 weeks after exposure, restores the lowered nociceptive sensitivity. Therefore, stimulating the vagus nerve appears to influence nociception. Future studies are need to elucidate possible mechanisms of this effect.

Prognostication of Survival Outcomes in Patients Diagnosed with Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with dismal survival. This study aims to examine the prognostic value of primary tumor sites and race on survival outcomes. METHODS: Patient data obtained from the Scott and White Hospital Brain Tumor Registry (1976-2013) were stratified according to sex, age, race, primary tumor site, vital status, and survival. RESULTS: Of the 645 patients, 580 (89.9%) were diagnosed with GBM not otherwise specified (GBM NOS), 57 (8.8%) with GBM, and 8 (1.2%) with giant-cell GBM. Most were male (53.5%), aged 50 years or older (78.7%). The white population had the highest GBM prevalence (87.1%) and the lowest overall survival versus all other race groups (6.6% vs. 30.1%; P < 0.01). The black population had a relatively low prevalence of GBM (5.9%) and the greatest overall survival versus all others (47.4% vs. 7.3%; P < 0.01). Primary tumor sites located in the temporal (25.8% vs. 20.2%; P = 0.03), occipital (8.1% vs. 2.9%; P = 0.05), and parietal lobes (24.2% vs. 20.8%; P = 0.05) had a greater occurrence in surviving individuals. The overall survival for men versus women was (62.9% vs. 37.1%; P = 0.12). CONCLUSIONS: Black racial background and temporal, occipital, or parietal primary tumor sites are suggestive of positive survival outcomes. Conversely, white racial background with primary tumor sites in the brain overlapping and NOS areas seem to be associated with negative outcomes and decreased survival. Thus, racial background and primary tumor site may be useful prognostic factors in patients with GBM.

Overview of Traumatic Brain Injury: An Immunological Context.

Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated with TBIs and for the chronic neuropathological and neurobehavioral deficits. Inflammation and neuroinflammation appear to be major mediators of TBI outcomes. These systems are being intensively studies using animal models and human translational studies, in the hopes of understanding the mechanisms of TBI, and developing therapeutic strategies to improve the outcomes of the millions of people impacted by TBIs each year. This manuscript provides an overview of the epidemiology and outcomes of TBI, and presents data obtained from animal and human studies focusing on an inflammatory and immunological context. Such a context is timely, as recent studies blur the traditional understanding of an "immune-privileged" central nervous system. In presenting the evidence for specific, adaptive immune response after TBI, it is hoped that future studies will be interpreted using a broader perspective that includes the contributions of the peripheral immune system, to central nervous system disorders, notably TBI and post-traumatic syndromes.

Intravascular Lymphoma in the CNS: Options for Treatment.

Purpose of review The purpose of this review was to discuss therapeutic manipulations and effective current interventions available to treat intravascular lymphoma in the central nervous system. Recent findings Patients experienced resolution and remission of disease for 14 months and up to 2 years after eight cycles of R-CHOP and four courses of intrathecal therapy with MTX, cytarabine, and prednisolone. Intravascular use of unfractionated heparin during therapy may contribute to better outcome. Summary Series of therapeutic avenues were analyzed and compared. The effective current treatment of intravascular lymphoma in the CNS is considered to be a combinational intrathecal methotrexate-based chemotherapy with rituximab. Since intrathecal administration bypasses the blood-brain barrier, lower doses can be given, which thereby minimizes systemic toxicity. Practical use of intrathecal chemotherapy is also justified for prophylaxis in intravascular lymphoma-diagnosed patients without CNS involvement.

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury.

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action.