The efficient noninvasive treatment of neurodegenerative disorders is often constrained by reduced permeation of therapeutic agents into the central nervous system (CNS). A vast majority of bioactive agents do not readily permeate into the brain tissue due to the existence of the blood-brain barrier (BBB) and the associated P-glycoprotein efflux transporter. The overexpression of the MDR1 P-gly...

Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood-brain barrier (BBB), blood-CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood-CNS exchange. The structure and function of the BBB is summa...

Extracellular vesicles (EVs) are particles released by multiple cells, encapsulated lipid bilayers and containing a variety of biological materials, including proteins, nucleic acids, lipids metabolites. With the advancement separation characterization methods, EV subtypes their complex diverse functions have been recognized. In central nervous system (CNS), EVs involved in various physiologica...

Utilization of neuropharmaceuticals for central nervous system(CNS) disease is highly limited due to the blood-brain barrier(BBB) which restricts molecules larger than 500Da from reaching the CNS. The development of a reliable method to bypass the BBB would represent an enormous advance in neuropharmacology enabling the use of many potential disease modifying therapies. Previous attempts such a...

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the t...

Schizophrenia is a devastating mental illness which can seriously compromise the lives of those afflicted, as well as their caretakers and family members. Historically, the cause of this illness has been attributed to demonic possession, sinful behavior, bad parenting, or even the season of the year when the subject was born. Various and sundry interventions have been employed over the years to...

Bupropion hydrochloride ((±)-2-tert-butylamino)-3 -chloropropiophenone · HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, b...

Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid â-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronat...

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain (24,32,40). It has been well documented that the reduction of GABAergic neuronal activity plays an important role in a number of neurological disorders, including epilepsy, anxiety, and pain (17). GABA is synthesized in nerve endings by the transamination of α-ketoglutaraldehyde to glutamic acid, which is...

Monoamine oxidase (MAO) is an enzyme that metabolizes a wide range of monoamines and is important in the control of the concentration of these neurotransmitters. Several reports have shown that stress can decrease MAO inhibitory activity. An endogenous MAO inhibitory component was first discovered in normal human urine by Glover et al. (22), and the compound responsible for the MAO activity was...