Brain pathology
-
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only therapeutic approach that can arrest cerebral demyelination of X-linked adrenoleukodystrophy (ALD) in boys and results in long-term in a good quality of life, provided the procedure is performed at an early stage of disease. Similar benefits of allogeneic HSCT have been demonstrated in adults with cerebral ALD. However, it is not yet known whether allogeneic HSCT can prevent or rescue adrenomyeloneuropathy. ⋯ The absence of biological markers that can predict the evolutivity of cerebral disease is a major limitation to propose in due time allogeneic HSCT to ALD patients. Recently, HSC gene therapy using lentiviral vector was shown to have comparable efficacy than allogeneic HSCT in two boys with cerebral ALD who had no Human-leukocyte-antigen (HLA)-matched donor. If these results are confirmed in an extended series of patients, HSC gene therapy may become the first therapeutic option for all ALD male patients who develop cerebral demyelination.
-
The prognosis of patients with malignant glioma is poor in spite of multimodal treatment approaches consisting of neurosurgery, radiochemotherapy and maintenance chemotherapy. Among innovative treatment strategies like targeted therapy, antiangiogenesis and gene therapy approaches, immunotherapy emerges as a meaningful and feasible treatment approach for inducing long-term survival in at least a subpopulation of these patients. ⋯ In the translational research program of the authors, the whole cascade from bench to bed to bench of active specific immunotherapy for malignant glioma is covered, including proof of principle experiments to demonstrate immunogenicity of patient-derived mature DCs loaded with autologous tumor lysate, preclinical in vivo experiments in a murine orthotopic glioma model, early phase I/II clinical trials for relapsing patients, a phase II trial for patients with newly diagnosed glioblastoma (GBM) for whom immunotherapy is integrated in the current multimodal treatment, and laboratory analyses of patient samples. The strategies and results of this program are discussed in the light of the internationally available scientific literature in this fast-moving field of basic science and translational clinical research.
-
Review
Immunotherapy of diffuse gliomas: biological background, current status and future developments.
Despite aggressive multimodal treatment approaches, the prognosis for patients with diffuse gliomas remains disappointing. Glioma cells often extensively infiltrate in the surrounding brain parenchyma, a phenomenon that helps them to escape surgical removal, radiation exposure and chemotherapy. Moreover, conventional therapy is often associated with considerable local and systemic side effects. ⋯ Immunotherapy offers the opportunity to specifically target residual radio-and chemoresistant tumor cells without damaging healthy neighboring brain tissue. Significant progress has been made in recent years both in understanding the mechanisms of immune regulation in the central nervous system (CNS) as well as tumor-induced and host-mediated immunosuppression elicited by gliomas. In this review, after discussing the special requirements needed for the initiation and control of immune responses in the CNS, we focus on immunological phenomena observed in glioma patients, discuss different immunological approaches to attack glioma-associated target structures and touch on further strategies to improve the efficacy of immunotherapy of gliomas.
-
This article will discuss accidental head injuries in infants and young children. The first category of injury is the crushing head injury. Static forces applied slowly to the head result in multiple fractures of the skull and contusions and lacerations of the brain resulting from the bone fragments striking the brain. ⋯ In about 1% of the fractures, an epidural or subdural hemorrhage occurs. Each of these forms of contact hemorrhages will be discussed and illustrated. While these are relatively rare injuries, it is essential that they can be identified as consistent with an accidental mechanism so that an erroneous diagnosis of inflicted injury is not made.
-
Small regulatory RNAs are essential and ubiquitous riboregulators that are the key mediators of RNA interference (RNAi). They include microRNAs (miRNAs) and short-interfering RNAs (siRNAs), classes of approximately 22 nucleotide RNAs. miRNAs and siRNAs bind to Argonaute proteins and form effector complexes that regulate gene expression; in animals, this regulation occurs primarily at the post-transcriptional level. In this review, we will discuss our current understanding of how miRNA and siRNAs are generated and how they function to silence gene expression, focusing on animal and, in particular, mammalian miRNAs.