We report on the enhanced optical transmittance in the NIR wavelength range (900 to 2400 nm) offered by a transparent Yttria-stabilized zirconia (YSZ) implant coupled with optical clearing agents (OCAs). The enhancement in optical access to the brain is evaluated upon comparing ex-vivo transmittance measurements of mice native skull and the YSZ cranial implant with scalp and OCAs. An increase in transmittance of up to 50% and attenuation lengths of up to 2.4 mm (i.e., a five-fold increase in light penetration) are obtained with the YSZ implant and the OCAs. The use of this ceramic implant and the biocompatible optical clearing agents offer attractive features for NIR optical techniques for brain theranostics.
Learning Objectives: After reading this article, the participant should be able to: 1. Identify the clinical syndrome of spontaneous intracranial hypotension. 2. Describe the diagnostic workup and imaging findings in patients with spontaneous intracranial hypotension. 3. Describe the guidelines and treatment options used in the management of spontaneous intracranial hypotension.
Molecular diffusion in the brain extracellular space (ECS) is an important determinant of neural function. We developed a brain surface photobleaching method to measure the diffusion of fluorescently labeled macromolecules in the ECS of the cerebral cortex. The ECS in mouse brain was labeled by exposure of the intact dura to fluorescein-dextrans ( M r 4, 70, and 500 kDa). Fluorescein-dextran diffusion, detected by fluorescence recovery after laser-induced cortical photobleaching using confocal optics, was slowed approximately threefold in the brain ECS relative to solution. Cytotoxic brain edema (produced by water intoxication) or seizure activity (produced by convulsants) slowed diffusion by >10-fold and created dead-space microdomains in which free diffusion was prevented. The hindrance to diffusion was greater for the larger fluorescein-dextrans. Interestingly, slowed ECS diffusion preceded electroencephalographic seizure activity. In contrast to the slowed diffusion produced by brain edema and seizure activity, diffusion in the ECS was faster in mice lacking aquaporin-4 (AQP4), an astroglial water channel that facilitates fluid movement between cells and the ECS. Our results establish a minimally invasive method to quantify diffusion in the brain ECS in vivo , revealing stimulus-induced changes in molecular diffusion in the ECS with unprecedented spatial and temporal resolution. The in vivo mouse data provide evidence for: (1) dead-space ECS microdomains after brain swelling; (2) slowed molecular diffusion in the ECS as an early predictor of impending seizure activity; and (3) a novel role for AQP4 as a regulator of brain ECS.
Over the course of the development of deep brain stimulation (DBS) into a well-established therapy for Parkinson’s disease, essential tremor, and dystonia, its utility as a potential treatment for autonomic dysfunction has emerged. Dysfunction of autonomic processes is common in neurological diseases. Depending on the specific target in the brain, DBS has been shown to raise or lower blood pressure, normalize the baroreflex, to alter the caliber of bronchioles, and eliminate hyperhidrosis, all through modulation of the sympathetic nervous system. It has also been shown to improve cortical control of the bladder, directly induce or inhibit the micturition reflex, and to improve deglutition and gastric emptying. In this review, we will attempt to summarize the relevant available studies describing these effects of DBS on autonomic function, which vary greatly in character and magnitude with respect to stimulation target.
The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force initiated the TASK3 working group to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve the standardization of experimental designs. This article addresses neuropathological changes associated with seizures and epilepsy in rodent models of epilepsy. We discuss CDEs for histopathological parameters for neurodegeneration, changes in astrocyte morphology and function, mechanisms of inflammation, and changes in the blood-brain barrier and myelin/oligodendrocytes resulting from recurrent seizures in rats and mice. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript, we discuss the rationale and methodological aspects of individual neuropathological examinations. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of rational therapy concepts for treating epilepsies, seizures, and comorbidities and the development of biomarkers assessing the pathological state of the disease.
Cerebral edema is a significant cause of morbidity and mortality in diverse disease states. Currently, the means to detect progressive cerebral edema in vivo includes the use of intracranial pressure (ICP) monitors and/or serial radiological studies. However, ICP measurements exhibit a high degree of variability, and ICP monitors detect edema only after it becomes sufficient to significantly raise ICP. The authors report the development of 2 distinct minimally invasive fiberoptic near-infrared (NIR) techniques able to directly detect early cerebral edema.Cytotoxic brain edema was induced in adult CD1 mice via water intoxication by intraperitoneal water administration (30% body weight intraperitoneally). An implantable dual-fiberoptic probe was stereotactically placed into the cerebral cortex and connected to optical source and detector hardware. Optical sources consisted of either broadband halogen illumination or a single-wavelength NIR laser diode, and the detector was a sensitive NIR spectrometer or optical power meter. In one subset of animals, a left-sided craniectomy was performed to obtain cortical biopsies for water-content determination to verify cerebral edema. In another subset of animals, an ICP transducer was placed on the contralateral cortex, which was synchronized to a computer and time stamped.Using either broadband illumination with NIR spectroscopy or single-wavelength laser diode illumination with optical power meter detection, the authors detected a reduction in NIR optical reflectance during early cerebral edema. The time intervals between water injection (Time Point 0), optical trigger (defined as a 2-SD change in optical reflectance from baseline), and defined threshold ICP values of 10, 15 and 20 mm Hg were calculated. Reduction in NIR reflectance occurred significantly earlier than any of the ICP thresholds (p < 0.001). Saline-injected control mice exhibited a steady baseline optical signal. There was a significant correlation between reflectance change and tissue specific gravity of the cortical biopsies, further validating the dual-fiberoptic probe as a direct measure of cerebral edema.Compared with traditional ICP monitoring, the aforementioned minimally invasive NIR techniques allow for the significantly earlier detection of cerebral edema, which may be of clinical utility in the identification and thus early treatment of cerebral edema.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
