Aspects herein relate to systems and methods for delivery of biologic agents to the central nervous system. In various embodiments, a method of administering a therapeutic agent to the central nervous system (CNS) is included. The method can include injecting a therapeutic agent into a first cerebrospinal fluid (CSF) region of the subject. The method can further include establishing fluid communication between a fluid reservoir and a second cerebrospinal fluid (CSF) region of a subject, the fluid having a hydraulic pressure at or above an intracranial pressure. The method can further include infusing a hyperosmotic fluid systemically. Other embodiments, including kits and systems are also included herein.

Provided herein are antibodies against amyloid-beta (Aβ) oligomers, and methods of use thereof for the treatment of Alzheimer's disease (AD). In particular, neuronal expression of single-chain variable fragment (scFv) antibodies against Aβ oligomers is provided as a therapeutic approach in the treatment of AD.

The present disclosure encompasses compositions and methods for effectively treating at least one symptom or sign of Aß plaque or cerebral amyloid angiopathy (CAA) associated symptoms, or for decreasing amyloid plaque load or CAA load. The method comprises administering an effective amount of an anti-ApoE antibody to a mammalian subject, such as to a human.

A method of treating a subject which may be a human suffering from epilepsy which may be a form of epilepsy resistant to treatment and particular patients which are resistant to treatment with oral medication. The method involves positioning a catheter device in the subject's brain and infusing a liquid formulation of a drug into a portion of the subject's brain through an infusion lumen at a rate of 5, 4, 3, 2, or 1 ml or less per day ±50%. The infusion may be constant and corrected by aspirating fluid from the patient's brain and testing the aspirated fluid for drug concentration. The rate of infusion by the formulation and the concentration of drug may be adjusted based on patient responsiveness.

A lipid nano drug delivery system targeting a brain lesion and a preparation method and application thereof. The drug delivery system comprises a lipid, a delivery drug, and a functional penetrating peptide, and the functional penetrating peptide is formed by covalently connecting a peptide chain linking a nanocarrier end, an arginine-rich penetrating peptide, a matrix metalloproteinase-9 sensitive peptide, and a polyanion inhibitory peptide. The lipid nano drug delivery system can be used for targeting the brain lesion and realizing mitochondrial enrichment by means of modification of the functional penetrating peptide. The repair of mitochondria is realized by encapsulating peptide drug cyclosporin A by means of a lipid nanoparticle core by utilizing a dilution-induced precipitation technique, thereby solving the problems that current cyclosporin A is difficult to effectively reach a brain lesion and the therapeutic window is small, and improving the ability to repair cells around the brain lesion with a small administration dose.

Devices for and related methods of treating a subject having a neurological injury to prevent or mitigate secondary injury are described. In an example, the devices include a base and a plurality of microneedles protruding from the base, the microneedles including a biocompatible and biodegradable matrix, and a neurologically active ingredient disposed within the matrix. In an example, a portion of the plurality of microneedles is shaped to penetrate the dura when the device is placed in contact with the dura.

Provided herein are novel methods for delivering recombinant adeno-associated viral (rAAV) particles to the central nervous system of a mammal (e.g., a human). In aspects, the methods involve administering rAAV particles containing a heterologous nucleic acid to the striatum and causing expression of the heterologous nucleic acid in at least the cerebral cortex and the striatum of the mammal.

Protein-based nanoparticles and methods of forming such protein-based nanoparticles via electrohydrodynamic jetting methods are provided. The nanoparticle may comprise a water-soluble protein having an average molecular weight of ≥ about 8 kDa and < about 700 kDa. In certain variations, the water-soluble protein is cross-linked (e.g., with an optional crosslinking agent) and defines a mesh structure having an average linear mesh size of ≥ about 1 nm to ≤ about 4 nm. Methods of making such nanoparticles may include jetting a liquid comprising the water-soluble protein through a nozzle, followed by exposing the liquid to an electric field sufficient to solidify the liquid and form the protein-based nanoparticles described above.

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Disclosed are methods of treating a subject following a small-volume ischemic stroke suffered by the subject and methods of treating a subject with a stroke-induced motor deficit. Disclosed also is a composition for treating small-volume ischemic stroke. In one aspect, the method of treating a subject following a small-volume ischemic stroke comprises administering, to a brain region surrounding a small-volume ischemic core of the subject, a therapeutically effective amount of cells, wherein the cells are descended from mesenchymal stem cells transiently-transfected by a polynucleotide encoding a Notch intracellular domain.

Provided herein are compositions and methods for diagnosis and therapy through targeted nano-delivery to injured brain endothelium. In some aspects, the compositions comprise a population of polyester derived nanoparticles, wherein each polyester derived nanoparticle comprises a) a therapeutic agent encapsulated therein for treating traumatically injured, inflamed, diseased, or disrupted endothelial cells, and b) a targeting ligand bound to the nanoparticle, wherein the targeting ligand binds to a biomarker for the injured, inflamed, diseased, or disrupted endothelial cells, are provided. The nanoparticles can be used for targeting difficult-to-reach injury sites, including the blood brain barrier and brain tissue.