ABSTRACT
The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of Gata3- and Foxp3-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress.
Subject(s)
Adrenal Cortex Hormones/metabolism , Brain/immunology , Stress, Psychological/metabolism , Adrenal Cortex Hormones/cerebrospinal fluid , Adrenal Cortex Hormones/immunology , Animals , Behavior, Animal , Brain/metabolism , Choroid Plexus/metabolism , Choroid Plexus/physiopathology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , GATA3 Transcription Factor/metabolism , Hormone Antagonists/pharmacology , Humans , Mice, Inbred C57BL , Mice, Mutant Strains , Mifepristone/pharmacology , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Signal Transduction , Single-Cell Analysis , Stress, Psychological/immunology , T-Lymphocytes/immunologyABSTRACT
The ability to respond to a wide range of novel touch sensations and to habituate upon repeated exposures is fundamental for effective sensation. In this study we identified adult spinal cord neurogenesis as a potential novel player in the mechanism of tactile sensation. We demonstrate that a single exposure to a novel mechanosensory stimulus induced immediate proliferation of progenitor cells in the spinal dorsal horn, whereas repeated exposures to the same stimulus induced neuronal differentiation and survival. Most of the newly formed neurons differentiated toward a GABAergic fate. This touch-induced neurogenesis reflected the novelty of the stimuli, its diversity, as well as stimulus duration. Introducing adult neurogenesis as a potential mechanism of response to a novel stimulus and for habituation to repeated sensory exposures opens up potential new directions in treating hypersensitivity, pain and other mechanosensory disorders.
Subject(s)
Neurogenesis/physiology , Neurons/physiology , Spinal Cord/cytology , Touch/physiology , Analysis of Variance , Animals , Bromodeoxyuridine/metabolism , Cell Count , Cell Differentiation , Cell Proliferation , Doublecortin Domain Proteins , Environment , Gene Expression Regulation/physiology , Male , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuropeptides/metabolism , Physical Stimulation/methods , Spinal Nerve Roots/cytology , Time Factors , gamma-Aminobutyric Acid/metabolismABSTRACT
This article describes in detail the indications for this radical procedure involving permanent removal of the toenail. A discussion of the surgical technique, including illustrations, is presented. Rationalization of the Distal Digital Symes Procedure is supported.
Subject(s)
Amputation, Surgical/methods , Nail Diseases/surgery , Surgical Flaps/methods , Foot Dermatoses/surgery , Hallux/surgery , HumansABSTRACT
The treatment of plantar verrucae has always been a challenging and perplexing problem to physicians. Due to the inherent nature of verrucae, response to various forms of treatment has been extremely unpredictable. It is believed that hyperhidrosis and abnormal pressure to the plantar aspects of the feet are contributing factors predisposing one to developing verrucae. This article describes a painless and effective approach to the treatment of plantar verruca through the use of blunt dissection. Following anesthesia obtained with a posterior tibial nerve block, the plantar verruca can be successfully dissected with an 80 percent cure rate.
Subject(s)
Dissection/methods , Foot Diseases/surgery , Warts/surgery , Adolescent , Child , Foot Diseases/diagnosis , Humans , Warts/diagnosisABSTRACT
Dr. Baruch presents some of the most common pediatric lower extremity skin conditions seen in clinical practice. The conditions that he discusses appear to be relatively easy to diagnose in the early stages; however, some of them, such as contact dermatitis and atopic dermatitis, may be hard to distinguish from one another. I have to admit that I have never seen lichen planus in the pediatric age group; I will need to keep looking. I agree with Dr. Baruch that classification of lesions into either the primary and secondary groups will aid in diagnosis and treatment. It also seems that the ever-present verrucae is the most common pediatric condition seen in our office, and we have taken similar steps in treating this condition with blunt dissection with excellent results.