Effects of essential oils on central nervous system: Focus on mental health.

Essential oils have been used as remedies since ancient times for the treatment of numerous illnesses on account of their wide range of biological activities. Recent preclinical and clinical studies have shown varying pharmacological responses in the nervous system leading to anxiolytic, antidepressant, sedative, and anticonvulsant effects. Experimentation in animal models has evidenced the involvement of multiple neurotransmitter systems in the mode of action of essential oils, resulting in measurable physiological effects in the brain. Additionally, clinical trials have demonstrated the influence of essential oils in physiological parameters such as blood pressure, heart rate, respiratory rate, brain waves composition, and cortisol serum levels with concomitant psychological effects. Although there is growing evidence of measurable effects of essential oils in animal brains, more clinical research is required to validate their influence in the human central nervous system. This will enable the development of essential oil-based drugs for the treatment of mental illnesses such as depression, anxiety and dementia.

Medium chain length polyhydroxyalkanoates as potential matrix materials for peripheral nerve regeneration.

Polyhydroxyalkanoates are natural, biodegradable, thermoplastic and sustainable polymers with a huge potential in fabrication of bioresorbable implantable devices for tissue engineering. We describe a comparative evaluation of three medium chain length polyhydroxyalkanoates (mcl-PHAs), namely poly(3-hydroxyoctanoate), poly(3-hydroxyoctanoate-co-3-hydoxydecanoate) and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate), one short chain length polyhydroxyalkanoate, poly(3-hydroxybutyrate), P(3HB) and synthetic aliphatic polyesters (polycaprolactone and polylactide) with a specific focus on nerve regeneration, due to mechanical properties of mcl-PHAs closely matching nerve tissues. In vitro biological studies with NG108-15 neuronal cell and primary Schwann cells did not show a cytotoxic effect of the materials on both cell types. All mcl-PHAs supported cell adhesion and viability. Among the three mcl-PHAs, P(3HO-co-3HD) exhibited superior properties with regards to numbers of cells adhered and viable cells for both cell types, number of neurite extensions from NG108-15 cells, average length of neurite extensions and Schwann cells. Although, similar characteristics were observed for flat P(3HB) surfaces, high rigidity of this biomaterial, and FDA-approved polymers such as PLLA, limits their applications in peripheral nerve regeneration. Therefore, we have designed, synthesized and evaluated these materials for nerve tissue engineering and regenerative medicine, the interaction of mcl-PHAs with neuronal and Schwann cells, identifying mcl-PHAs as excellent materials to enhance nerve regeneration and potentially their clinical application in peripheral nerve repair.

A new era for schizophrenia drug development - Lessons for the future.

For many patients and their treating clinicians, the pharmacological management of psychotic symptoms centres on trying to find a regime that balances efficacy and quality of life-impairing side effects associated with dopamine antagonism. Recent reports of a positive Phase III study from Karuna Therapeutics indicate that the first primarily non-dopamine-based treatment for schizophrenia may come to market soon with the potential for substantially reduced or differentiated side effects. Against a background of repeated failures, Karuna's success promises a desperately needed new treatment option for patients. It also reflects some hard-won lessons about the methodology for schizophrenia drug development.

Extracellular vesicles and intercellular communication in the central nervous system.

Neurons and glial cells of the central nervous system (CNS) release extracellular vesicles (EVs) to the interstitial fluid of the brain and spinal cord parenchyma. EVs contain proteins, nucleic acids and lipids that can be taken up by, and modulate the behaviour of, neighbouring recipient cells. The functions of EVs have been extensively studied in the context of neurodegenerative diseases. However, mechanisms involved in EV-mediated neuron-glial communication under physiological conditions or healthy ageing remain unclear. A better understanding of the myriad roles of EVs in CNS homeostasis is essential for the development of novel therapeutics to alleviate and reverse neurological disturbances of ageing. Proteomic studies are beginning to reveal cell type-specific EV cargo signatures that may one day allow us to target specific neuronal or glial cell populations in the treatment of debilitating neurological disorders. This review aims to synthesise the current literature regarding EV-mediated cell-cell communication in the brain, predominantly under physiological conditions.

Preclinical study of peripheral nerve regeneration using nerve guidance conduits based on polyhydroxyalkanaotes.

Nerve guidance conduits (NGCs) are used as an alternative to the "gold standard" nerve autografting, preventing the need for surgical intervention required to harvest autologous nerves. However, the regeneration outcomes achieved with the current NGCs are only comparable with autografting when the gap is short (less than 10 mm). In the present study, we have developed NGCs made from a blend of polyhydroxyalkanoates, a family of natural resorbable polymers. Hollow NGCs made from a 75:25 poly(3-hydroxyoctanoate)/poly(3-hydroxybutyrate) blend (PHA-NGCs) were manufactured using dip-molding. These PHA-NGCs showed appropriate flexibility for peripheral nerve regeneration. In vitro cell studies performed using RT4-D6P2T rat Schwann cell line confirmed that the material is capable of sustaining cell proliferation and adhesion. PHA-NGCs were then implanted in vivo to repair 10 mm gaps of the median nerve of female Wistar rats for 12 weeks. Functional evaluation of the regenerated nerve using the grasping test showed that PHA-NGCs displayed similar motor recovery as the autograft, starting from week 7. Additionally, nerve cross-sectional area, density and number of myelinated cells, as well as axon diameter, fiber diameter, myelin thickness and g-ratio obtained using the PHA-NGCs were found comparable to an autograft. This preclinical data confirmed that the PHA-NGCs are indeed highly promising candidates for peripheral nerve regeneration.

Modulation of neuronal cell affinity of composite scaffolds based on polyhydroxyalkanoates and bioactive glasses.

The biocompatibility and neuron regenerating properties of various bioactive glass (BG)/polyhydroxyalkanoate (PHA) blend composites were assessed in order to study their suitability for peripheral nerve tissue applications, specifically as lumen structures for nerve guidance conduits. BG/PHA blend composites were fabricated using Bioactive glass® 45 S5 (BG1) and BG 1393 (BG2) with the 25:75 poly(3-hydroxyoctanoate/poly3-hydroxybutyrate), 25:75 P(3HO)/P(3HB) blend (PHA blend). Various concentrations of each BG (0.5 wt%, 1.0 wt% and 2.5 wt%) were used to determine the effect of BG on neuronal growth and differentiation, in single culture using NG108-15 neuronal cells and in a co-culture along with RN22 Schwann cells. NG108-15 cells exhibited good growth and differentiation on all the PHA blend composites showing that both BGs have good biocompatibility at 0.5 wt%, 1.0 wt% and 2.5 wt% within the PHA blend. The Young's modulus values displayed by all the PHA blend/BG composites ranged from 385.6 MPa to 1792.6 MPa, which are able to provide the required support and protective effect for the regeneration of peripheral nerves. More specifically, the tensile strength obtained in the PHA blend/BG1 (1.0 wt%) (10.0 ± 0.6 MPa) was found to be similar to that of the rabbit peroneal nerve. This composite also exhibited the best biological performance in supporting growth and neuronal differentiation among all the substrates. The neurite extension on this composite was found to be remarkable with the neurites forming a complex connection network.

Unidirectional neuronal cell growth and differentiation on aligned polyhydroxyalkanoate blend microfibres with varying diameters.

Polyhydroxyalkanoates (PHAs) are a family of prokaryotic-derived biodegradable and biocompatible natural polymers known to exhibit neuroregenerative properties. In this work, poly(3-hydroxybutyrate), P(3HB), and poly(3-hydroxyoctanoate), P(3HO), have been combined to form blend fibres for directional guidance of neuronal cell growth and differentiation. A 25:75 P(3HO)/P(3HB) blend (PHA blend) was used for the manufacturing of electrospun fibres as resorbable scaffolds to be used as internal guidance lumen structures in nerve conduits. The biocompatibility of these fibres was studied using neuronal and Schwann cells. Highly aligned and uniform fibres with varying diameters were fabricated by controlling electrospinning parameters. The resulting fibre diameters were 2.4 ± 0.3, 3.7 ± 0.3, and 13.5 ± 2.3 µm for small, medium, and large diameter fibres, respectively. The cell response to these electrospun fibres was investigated with respect to growth and differentiation. Cell migration observed on the electrospun fibres showed topographical guidance in accordance with the direction of the fibres. The correlation between fibre diameter and neuronal growth under two conditions, individually and in coculture with Schwann cells, was evaluated. Results obtained from both assays revealed that all PHA blend fibre groups were able to support growth and guide aligned distribution of neuronal cells, and there was a direct correlation between the fibre diameter and neuronal growth and differentiation. This work has led to the development of a family of unique biodegradable and highly biocompatible 3D substrates capable of guiding and facilitating the growth, proliferation, and differentiation of neuronal cells as internal structures within nerve conduits.