In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.

Dietary polyphenols represent a phytotherapeutic alternative for gut dysbiosis associated neurodegeneration: A systematic review.

Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.

Saccharomyces boulardii ameliorates gut dysbiosis associated cognitive decline.

Saccharomyces boulardii, a probiotic yeast is well prescribed for various gastrointestinal disorders accompanied by gut dysbiosis such as inflammatory bowel disease, bacterial diarrhea and antibiotic associated diarrhea. Gut dysbiosis has been associated with central nervous system via gut brain axis primarily implied in the modulation of psychiatric conditions. In the current study we use Saccharomyces boulardii as a therapeutic agent against gut dysbiosis associated cognitive decline. In mice, gut dysbiosis was induced by oral Ampicillin Na (250 mg/kg twice-daily) for 14 days. While in the treatment group S. boulardii (90 mg/kg once a day) was administered orally for 21 days along with 14 days of antibiotic treatment. Gene expression studies revealed antibiotic mediated decrease in the Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were restored by S. boulardii treatment. Cognitive behavioral studies showed a parallel reduction in fear conditioning, spatial as well as recognition memory which were reversed upon S. boulardii treatment in these animals. S. boulardii treatment reduced myeloperoxidase enzyme, an inflammatory marker, in colon as well as brain which was increased after antibiotic administration. Similarly, S. boulardii reduced the brain acetylcholine esterase, oxidative stress and inflammatory cytokines and chemokines which were altered due to antibiotic treatment. S. boulardii treatment also protected hippocampal neuronal damage and restored villus length and crypt depth thus normalizing gut permeability in antibiotic treated animals. Hence, we conclude that S. boulardii prevented antibiotic associated gut dysbiosis leading to reduced intestinal and brain inflammation and oxidative stress thus preventing hippocampal neuronal damage and eventually reversing gut dysbiosis associate cognitive decline in mice.

Probiotics protect against gut dysbiosis associated decline in learning and memory.

Gut-Brain-Axis imbalance due to gut dysbiosis by antibiotics may lead to neurobehavioral changes. Here we determine neuroprotective effect of probiotic against gut dysbiosis associated decline in learning and memory. Oral Ampicillin was used to induce gut dysbiosis while probiotic was administered along with antibiotic as treatment in Swiss albino mice. Antibiotic decreased Lactobacillus, Bifidobacterium, Firmicutes and Clostridium level. This was followed by reduced cognition, hippocampal neuronal density, intestinal crypt depth, villus length and increased corticohippocampal acetylcholinesterase, myeloperoxidase activity and oxidative stress which were partially reversed by probiotic treatment. Probiotic protected hippocampal neurons from gut dysbiosis associated inflammatory and oxidative damage in mice.

Gut microbiota in neurodegenerative disorders.

Gut dysbiosis, a primary factor behind various gastrointestinal disorders may also augment lipopolysaccharides, pro-inflammatory cytokines, T helper cells and monocytes causing increased intestinal and BBB permeability via microbiota-gut-brain axis. Consequentially, accumulation of misfolded proteins, axonal damage and neuronal demyelination sets in, thus facilitating the pathogenesis of neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. Studies revealed that intake of probiotics may help in the integrity of intestinal and BBB thus ameliorating the above neurodegenerative disorders. This review summarizes the current understanding of the role of gut microbiota in neurodegenerative disorders and possible intervention strategies.