Designing peptide nanoparticles for efficient brain delivery.

Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer's disease, Parkinson's disease, and stroke are explained.

/pdf/recent-strategies-for-targeted-brain-drug-delivery-50n3g2eplj.pdf

Recent Strategies for Targeted Brain Drug Delivery

Somatosensory Cortical Electrical Stimulation After Reperfusion Attenuates Ischemia/Reperfusion Injury of Rat Brain

Encoding artificial perceptions through brain stimulation, especially that of higher cognitive functions such as speech perception, is one of the most formidable challenges in brain-computer interfaces (BCI). Brain stimulation has been used for functional mapping in clinical practices for the last 70 years to treat various disorders affecting the nervous system, including epilepsy, Parkinson’s disease, essential tremors, and dystonia. Recently, direct electrical stimulation has been used to evoke various forms of perception in humans, ranging from sensorimotor, auditory, and visual to speech cognition. Successfully evoking and fine-tuning artificial perceptions could revolutionize communication for individuals with speech disorders and significantly enhance the capabilities of brain-computer interface technologies. However, despite the extensive literature on encoding various perceptions and the rising popularity of speech BCIs, inducing artificial speech perception is still largely unexplored, and its potential has yet to be determined. In this paper, we examine the various stimulation techniques used to evoke complex percepts and the target brain areas for the input of speech-like information. Finally, we discuss strategies to address the challenges of speech encoding and discuss the prospects of these approaches. 

Evoking artificial speech perception through invasive brain stimulation for brain-computer interfaces: current challenges and future perspectives

Brain-computer interfaces (BCIs) provide a communication interface between the brain and external devices and have the potential to restore communication and control in patients with neurological injury or disease. For the invasive BCIs, most studies recruited participants from hospitals requiring invasive device implantation. Three widely used clinical invasive devices that have the potential for BCIs applications include surface electrodes used in electrocorticography (ECoG) and depth electrodes used in Stereo-electroencephalography (SEEG) and deep brain stimulation (DBS). This review focused on BCIs research using surface (ECoG) and depth electrodes (including SEEG, and DBS electrodes) for movement decoding on human subjects. Unlike previous reviews, the findings presented here are from the perspective of the decoding target or task. In detail, five tasks will be considered, consisting of the kinematic decoding, kinetic decoding,identification of body parts, dexterous hand decoding, and motion intention decoding. The typical studies are surveyed and analyzed. The reviewed literature demonstrated a distributed motor-related network that spanned multiple brain regions. Comparison between surface and depth studies demonstrated that richer information can be obtained using surface electrodes. With regard to the decoding algorithms, deep learning exhibited superior performance using raw signals than traditional machine learning algorithms. Despite the promising achievement made by the open-loop BCIs, closed-loop BCIs with sensory feedback are still in their early stage, and the chronic implantation of both ECoG surface and depth electrodes has not been thoroughly evaluated. 

A Review of Motor Brain-Computer Interfaces using Intracranial Electroencephalography based on Surface Electrodes and Depth Electrodes

Electrical stimulation of the primary somatosensory cortex using intracranial electrodes is crucial for the evocation of artificial somatosensations, typically tactile sensations associated with specific regions of the body, in brain-machine interface (BMI) applications. The qualitative characteristics of these artificially evoked somatosensations has been well documented. As of yet, however, the quantitative aspects of these evoked somatosensations, that is to say the quantitative relationship between intensity of electrical stimulation and perceived intensity of the resultant somatosensation remains obscure. This study aimed to explore this quantitative relationship by surface electrical stimulation of the primary somatosensory cortex in two human participants undergoing electrocorticographic monitoring prior to surgical treatment of intractable epilepsy. Electrocorticogram electrodes on the primary somatosensory cortical surface were stimulated with varying current intensities, and a visual analogue scale was employed to provide a quantitative measure of intensity of the evoked sensations. Evoked sensations included those of the thumb, tongue, and hand. A clear linear relationship between current intensity and perceived intensity of sensation was observed. These findings provide novel insight into the quantitative nature of primary somatosensory cortex electrical stimulation-evoked sensation for development of somatosensory neuroprosthetics for clinical use.

/pdf/somatosensation-evoked-by-cortical-surface-stimulation-of-1kwxj0nddm.pdf

Somatosensation Evoked by Cortical Surface Stimulation of the Human Primary Somatosensory Cortex.

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Somatosensation Evoked by Cortical Surface Stimulation of the Human Primary Somatosensory Cortex.