Parkinson’s disease (PD) is a neurodegenerative illness and has a common onset between the ages of 55 and 65 years. There is progressive development of both motor and non-motor symptoms, greatly affecting one’s overall quality of life. While there is no cure, various treatments have been developed to help manage the symptoms of PD. Management of PD is a growing field and targets new treatment methods, as well as improvements to old ones. Pharmacological, surgical, and therapeutic treatments have allowed physicians to treat not only the main motor symptoms of PD, but target patient-specific problems as they arise. This review discusses both the established and new possibilities for PD treatment that can provide patient-specific care and mitigate side effects for common treatments.
Worldwide, spinal cord injury (SCI) affects around 500,000 people each year and results in significant morbidity. The primary insult to the spinal cord occurs at the time of the initial injury, which may result from a contusion, laceration or more rarely a transection. Secondary damage in SCI is more insidious and subacute; it is the result of a combination of an inflammatory response, vascular changes and ionic dysregulation. Early clinical intervention is vital after the acute, primary insult to ensure the best possible outcomes for these patients. Current evidence on the demographics and mechanisms, underlying basic science and management strategies of spinal cord injuries are outlined.
Multiple sclerosis (MS) is a lifelong inflammatory demyelinating disease of the central nervous system (CNS). While there has been substantial progress in the development of therapeutic strategies for relapsing disease, the field has lagged behind in its understanding and management of progressive stages of the disease, including secondary progressive and primary progressive MS, respectively. It is now thought that distinct but temporally overlapping mechanisms underlie relapsing and progressive aspects of the disease. Relapsing disease is characterized by waves of peripheral immune cell activation and CNS infiltration leading to focal destruction of the white matter, while progressive disease is thought to be driven by chronic, low-grade multifocal inflammation contained within the CNS compartment. Specifically, peripheral B cells, T cells, and myeloid cells take up residence within niches of the inflamed CNS, such as the leptomeninges and the Virchow-Robin spaces, where complex interactions between peripheral and CNS resident cells serve to maintain these cellular aggregates and further propagate CNS injury. In particular, immune infiltrates within the meninges are tightly associated with a specific form of cortical injury, termed subpial cortical demyelination, which is thought to be a key pathologic driver of disease progression. Cortical injury in the MS brain likely occurs via a combination of multiple immune-mediated and degenerative processes, perhaps including the production of diffusible toxic mediators by peripheral immune cells retained within the meninges. A better understanding of the interplay between peripheral immune and CNS resident cells is not only relevant to our concept of the disease process, but also represents a novel target for therapeutic intervention that is more specific to progressive disease biology. This review will focus on the role of CNS-compartmentalized inflammation in the development of cortical injury in MS, with a particular emphasis on the importance of immune-CNS crosstalk in disease progression.
Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.
Neuroaxonal loss is believed to underpin the progressive disability that characterizes multiple sclerosis (MS). While focal inflammatory demyelination is a principal cause of acute axonal transection and subsequent axonal degeneration, the gradual attrition of permanently demyelinated axons may also contribute to tissue damage, particularly in the progressive phase of the disease. Therefore, remyelination is considered a putative neuroprotective strategy. In this article, we review the potential pitfalls of remyelination trials, provide a framework for their appropriate design and temper the expectations, at times unrealistic, of researchers, regulators and the pharmaceutical industry.
Autoimmune epilepsy (AE) is a general term to describe recurrent seizures that have an immune-mediated origin. It is increasingly being recognized as a cause of epilepsy due to accumulating evidence supporting an immune-mediated pathogenesis in patients who have shown resistance to traditional antiepileptic drugs (AEDs). The diagnosis of AE is one of the exclusions. Currently, there are no strict diagnostic guidelines for AE, and it is similarly under-recognized. The importance of early diagnosis of AE cannot be overstated, as prompt immunotherapy is important for seizure reduction. Further investigations into potential biomarkers are needed for early detection of AE and include targeted immunotherapies in combination with AEDs. The goal of this review was to provide an overview of the following biomarkers that have been associated with AE: AMPAR, LGl1, CASPR2, DPPX, GABAAR, GABABR, GFAP, GlyR, mGluR5, NMDAR, VGCC (P/Q types), amphiphysin, ANNA-1, CRMP-5, GAD65, and Ma1/Ma2 antibodies.
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive neuron loses in memoryrelated brain structures. Five drugs have been approved by the FDA to treat Alzheimer’s disease; however, these drugs have failed to modify or significantly slow disease progression. New therapies are needed to delay the course of this disease and hopefully prevent further neuron losses. This review describes available AD drugs and several novel approaches presently being investigated. We next describe relevant biomarkers and urge greater research interest in the potential utilization of neurotrophic agents to treat AD. Neurotrophins such as nerve growth factor, brain-derived neurotrophic factor and hepatocyte growth factor (HGF) are capable of stimulating dendritic arborization, synaptogenesis, stem cell differentiation, neurogenesis, and decreases in neuroinflammation, oxidative stress-induced damage and neurotoxicity due to a wide range of cellular insults. We present the strategy of utilizing small molecule analogs specifically designed to penetrate the blood-brain barrier and facilitate dimerization and activation of the HGF/Met receptor system. These molecules have been shown to encourage the formation of new functional synaptic connections, induce long-term potentiation and augment memory consolidation and retrieval in animal models of AD. Such molecules may be appropriate for use at the first indication of mild cognitive impairment, and perhaps prophylactically in those individuals who are most likely to develop dementia due to genetic, health, behavioral and life-style predisposing factors.
Human primary brain cancer is one of the most lethal and clinically challenging malignancies. The failure of conventional therapies to alleviate its poor outcome has prompted efforts to find innovative treatments. Recent breakthroughs in immunotherapy across a variety of solid tumors have set immune-based therapeutics as a pillar for brain cancer treatment. However, the unique features of brain malignancies including intratumoral heterogeneity, immunosuppressive microenvironment, and impervious blood-brain barrier, thwart the success of immunotherapeutic approaches. Yet, seminal findings regarding tumor-driven enrichment of specific immune cells granted the field novel insights to harness the immune cells to fight cancer. This review discusses the anatomical, microenvironmental, and immunobiological features of the human brain and presents an overview of immunotherapies tested for primary brain cancer patients with a special emphasis on registered phase 2, 3, and combinatorial clinical trials. Immune checkpoint inhibitors, immune cell-based therapies, cancer vaccines, oncolytic viral therapy, and combination therapies are investigated in clinical settings for the treatment of human brain tumors. Despite their occasional adverse effects, immune-targeted therapies provide a promising opportunity for primary brain cancer patients to enhance survival and improve prognosis.
The new "severe acute respiratory syndrome" (SARS)-correlated coronavirus (SARS-CoV-2), first isolated from three patients from Wuhan (China), has been spreading worldwide since the end of 2019, emerging as an exceptional global crisis. This disorder was called "coronavirus disease 2019" or COVID-19. Clinical features are highly variable, and the clinical severity ranges from asymptomatic to fatal. The understanding of SARS-CoV-2 infection is ongoing. Several neurological symptoms were identified as part of the COVID-19 spectrum, including muscle pain, confusion, and headache[1].
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1％ of the worldwide population. Diagnosis of PD relies on clinical history and physical examination, but misdiagnosis is common in early stages. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease-modifying treatments. Increasing evidence suggests that autophagic dysregulation causes the accumulation of abnormal proteins, such as aberrant α-synuclein, a protein critical to PD pathogenesis. Mutations in the GBA gene are a major PD risk factor and β-glucocerebrosidase (GCase) is also emerging as an important molecule in PD pathogenesis. Consequently, proteins involved in the autophagy-lysosome pathway and GCase protein levels and activity are prime targets for the research and development of new PD biomarkers. The studies so far in PD biological material have yielded some consistent results, particularly regarding the levels of Hsc70, a component of the chaperone-mediated autophagy pathway, and the enzymatic activity of GCase in GBA mutation carriers. In the future, larger longitudinal studies, corroborating previous research on possible biomarker candidates, as well as extending the search for possible candidates for other lysosomal components, may yield more definitive results.
Cranial nerve involvement is rarely seen in chronic inflammatory demyelinating polyneuropathy (CIDP). We present a patient diagnosed with CIDP who was in a stable medical condition under long-term treatment with intravenous immunoglobulin (IVIG) every five weeks for more than seven years. Following a 12-day delay in the patient’s regular IVIG therapy, he developed acute bilateral vocal cord palsy. The patient had to be intubated and tracheostomized because of acute respiratory distress. Weaning from mechanical ventilation was complicated due to pneumonia. After antibiotic treatment and restarting IVIG therapy vocal cord palsy rapidly improved allowing for subsequent decannulation. Although coincidence between treatment delay and symptom development does not prove definitive causality this case report may serve as a reminder how time critical IVIG therapy can be for sufficient symptom control. Moreover, it provides evidence that IVIG therapy may be effective for the treatment of cranial nerve symptoms in CIDP.
Coronavirus disease-19 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus-2 and was declared a pandemic in March 2020. It mainly causes upper respiratory symptoms, but an interstitial viral pneumonia may occur, in severe cases complicated by acute respiratory distress syndrome. Neurological involvement has been reported but has not been well investigated. A 75-year old man presenting with severe COVID-19 related pneumonia developed a severe cognitive impairment and a right temporal hemianopsia, with focal microangiopathy and subacute ischemic alterations detected on brain imaging, interpreted as vasculitic-inflammatory injury. The neurological disorder was diagnosed only after he was extubated. A rehabilitation program was set up, so the patient had a complete cognitive recovery. Our case underlines how COVID-19 can lead to severe neurological sequelae, so neurological examination should be promptly performed when patients display signs of nervous system involvement, in order to prevent further damages.
Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease usually presenting with acute demyelinating events that can start as, or progress to, chronic damage. The development of animal experimental models, specific for each stage of MS will aid in the design of new drugs specific for the different forms of the disease. Animal models of experimental autoimmune encephalomyelitis successfully reflect the pathophysiological mechanisms of the early phases of MS. However, few models resemble the features of the progressive forms of MS such as cortical demyelination and meningeal inflammation. Recently, a few auspicious animal models recapitulating many of the characteristics of progressive MS, aimed at a better understanding of the pathology of these forms of the disease, have been developed. In this review, we will summarize the latest developments in animal models reflecting the cortical and meningeal pathological features of progressive MS, as well as their response to drugs specifically targeting these forms.
A provocative and overly reductive mantra is that "the back of the eye is the front of the brain". Retinal imaging techniques that take advantage of this "window" to the central nervous system can provide valuable information regarding injury to the nervous system with relative ease and with a limited burden to patients. The retina develops embryonically as part of the neuroectoderm, is made up principally of neurons and their supporting cells, and is synaptically tied to the central nervous system (CNS). This has led to significant interest in using retinal health as a biomarker for brain health - given the relatively limited accessibility of brain tissue in chronic neurodegenerative diseases that progress over decades. The retina is not truly part of the CNS, and as with much of brain imaging - the grounds for asserting the pathological specificity of retinal imaging is limited. Biophotonics-based methods such as optical coherence tomography indirectly provide an opportunity to evaluate retinal neurodegeneration, while autopsy studies, histology and immunohistochemistry predominate as the methods that collect direct pathological data. Our understanding of pathological retinal lesions characteristic of demyelinating diseases, specifically diseases showing anterior visual pathway involvement, has grown significantly in recent years. However, much of the underlying pathobiology of injury remain unexplored. This review aims to highlight the major pathological features of the retina in multiple sclerosis, and its most used animal models (experimental autoimmune encephalomyelitis and cuprizone), with a particular focus on n the role of inflammation.
OAE Publishing Inc. is an international scholarly publisher specializing in peer-reviewed academic journals. To promote academic exchange and knowledge sharing, OAE provides an outstanding academic platform for biomedical experts and scholars all over the world.
Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.
Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.
OAE Publishing Inc. is an international scholarly publisher specializing in peer-reviewed academic journals. To promote academic exchange and knowledge sharing, OAE provides an outstanding academic platform for biomedical experts and scholars all over the world.
OAE Publishing Inc. is an international scholarly publisher specializing in peer-reviewed academic journals. To promote academic exchange and knowledge sharing, OAE provides an outstanding academic platform for biomedical experts and scholars all over the world.
Spinal cord injury (SCI) is a debilitating injury that results from traumatic or non-traumatic insults to the spinal cord, causing significant impairment of the patient’s activity and quality of life. Bone morphogenic proteins (BMPs) are a group of polyfunctional cytokines belonging to the transforming growth factor beta superfamily that regulates a wide variety of cellular functions in healthy and disease states. Recent studies suggest that dysregulation of BMP signaling is involved in neuronal demyelination and death after traumatic SCI. The focus of this article is to describe our current understanding of the role of BMP signaling in the regulation of cell fate, proliferation, apoptosis, autophagy, and inflammation in traumatic SCI. First, we will describe the expression of BMPs and pattern of BMP signaling before and after traumatic SCI in rodent models and in vitro. Next, we will discuss the role of BMP in the regulation of neuronal and glial cell differentiation, survival, functional recovery from traumatic SCI, and the gap in knowledge in this area that requires further investigation to improve SCI prognosis.
