The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the different approaches employed to overcome this barrier, the use of nanoparticles as a tool to enhance delivery of therapeutic molecules to the brain is particularly promising. There is special interest in the use of magnetic nanoparticles, as their physical characteristics endow them with additional potentially useful properties. Following systemic administration, a magnetic field applied externally can mediate the capacity of magnetic nanoparticles to permeate the blood-brain barrier. Meanwhile, thermal energy released by magnetic nanoparticles under the influence of radiofrequency radiation can modulate blood-brain barrier integrity, increasing its permeability. In this review, we present the strategies that use magnetic nanoparticles, specifically iron oxide nanoparticles, to enhance drug delivery to the brain.

/pdf/magnetic-nanoparticles-cross-the-blood-brain-barrier-when-5d4ob9rn6s.pdf

Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge

This study demonstrates the clinical efficacy of Manasamitra Vataka and Shirodhara (Ayurvedic treatments) over clonazepam in preserving slow wave sleep and promoting sleep quality in patients of generalized anxiety disorder (GAD) with co-morbid generalized social phobia. Whole night polysomnography was carried out to assess the sleep architecture and spindle- delta dynamics. The study highlights the sleep promoting and preserving nature of Manasamitra Vataka and Shirodhara in GAD patients with co-morbid generalized social phobia. Ayurvedic treatments were helpful in improving the subjective quality of sleep and preserve sleep organization. Further studies are needed to confirm the potential of Ayurvedic interventions as a treatment of choice in the management of anxiety disorders.

Manasamitra vataka and Shirodhara Treatments Preserve Slow Wave Sleep and Promote Sleep Continuity in Patients with Generalized Anxiety Disorder and Co-Morbid Generalized Social Phobia

Disclosed is a method of treating or preventing a disease or disorder of the central nervous system (CNS) in a patient comprising administering transcranially, for example, directly to the skull, an effective amount of an anti-inflammatory agent to the patient. Examples of the anti-inflammatory agent include glutathione and inhibitors of purinergic receptors such as P2X4,P2X7, P2Y6, and P2Y12receptors. Examples of disease or disorder of the CNS include brain injury, particularly traumatic brain injury, inflammation, infection, degeneration of brain cells, stroke, brain edema, tumor, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Also disclosed is a kit comprising at least one anti-inflammatory agent and printed materials containing instructions for transcranially administering the anti-inflammatory agent to the patient having a disease or disorder of the CNS. isorder of the CNS.

Methods of treating and preventing diseases and disorders of the central nervous system

Appropriate vascular function is essential for the maintenance of central nervous system homeostasis and is achieved through virtue of the blood-brain barrier; a specialized structure consisting of endothelial, mural, and astrocytic interactions. While appropriate blood-brain barrier function is typically achieved, the central nervous system vasculature is not infallible and cerebrovascular anomalies, a collective terminology for diverse vascular lesions, are present in meningeal and cerebral vasculature supplying and draining the brain. These conditions, including aneurysmal formation and rupture, arteriovenous malformations, dural arteriovenous fistulas, and cerebral cavernous malformations, and their associated neurological sequelae, are typically managed with neurosurgical or pharmacological approaches. However, increasing evidence implicates interacting roles for inflammatory responses and disrupted central nervous system fluid flow with respect to vascular perturbations. Here, we discuss cerebrovascular anomalies from an immunologic angle and fluid flow perspective. We describe immune contributions, both common and distinct, to the formation and progression of diverse cerebrovascular anomalies. Next, we summarize how cerebrovascular anomalies precipitate diverse neurological sequelae, including seizures, hydrocephalus, and cognitive effects and possible contributions through the recently identified lymphatic and glymphatic systems. Finally, we speculate on and provide testable hypotheses for novel nonsurgical therapeutic approaches for alleviating neurological impairments arising from cerebrovascular anomalies, with a particular emphasis on the normalization of fluid flow and alleviation of inflammation through manipulations of the lymphatic and glymphatic central nervous system clearance pathways.

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow.

/pdf/bench-to-bedside-translation-of-magnetic-nanoparticles-316vnc5koi.pdf

Bench-to-bedside translation of magnetic nanoparticles.

Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about b activity in the electroencephalographic wave patterns and shortening of the sleep latency period Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design The study was under taken in two phases In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria In both phases of the study there was significant reduction in the sleep latencies It was much more pronounced in the Phase-II study None of the subjects however displayed beta activity in the electroencephalography Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation Transcranial brain targeted dosage design is therefore feasible

/pdf/brain-targeted-transcranial-administration-of-diazepam-and-2dbvinwm81.pdf

Brain targeted transcranial administration of diazepam and shortening of sleep latency in healthy human volunteers.

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Brain targeted transcranial administration of diazepam and shortening of sleep latency in healthy human volunteers.