Methods to promote myelin regeneration in response to central myelin loss are essential to prevent the progression of clinical disability in demyelinating diseases. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to promote myelination during development via oligodendrocyte expressed TrkB receptors. Here, we use a structural mimetic of BDNF to promote myelin regeneration in a preclinical mouse model of central demyelination. In female mice, we show that selective targeting of TrkB with the BDNF-mimetic enhances remyelination, increasing oligodendrocyte differentiation, the frequency of myelinated axons, and myelin sheath thickness after a demyelinating insult. Treatment with exogenous BDNF exerted an attenuated effect, increasing myelin sheath thickness only. Further, following conditional deletion of TrkB from premyelinating oligodendrocytes, we show the effects of the BDNF-mimetic on oligodendrocyte differentiation and remyelination are lost, indicating these are dependent on oligodendrocyte expression of TrkB. Overall, these studies demonstrate that targeting oligodendrocyte TrkB promotes remyelination in the brain. Novel strategies to promote myelin regeneration are required to prevent progressive neurodegeneration and clinical disability in patients with central demyelinating disease. Here, we test whether selectively targeting the TrkB receptor on the myelin-producing oligodendrocytes, can promote remyelination in the brain. Using a structural mimetic of its native ligand, BDNF, we show that stimulation of TrkB enhances remyelination, increasing oligodendrocyte differentiation, the frequency of myelinated axons and thickness of the myelin sheath following a demyelinating insult. Further, we show that these effects are dependent on the phosphorylation of oligodendrocyte expressed TrkB receptors Overall, we demonstrate that selective targeting of TrkB has therapeutic potential to promote remyelination in the brain.

Introduction: Hepatocellular carcinoma (HCC) carries significant burden of disease, with high mortality rates and poor prognosis. It is therefore important to consider quality of life (QoL) for patients with HCC. Quantitative research assesses HCC and QoL via standardised measurement tools, but these do not capture the full scope of patient experiences. This review examines the body of qualitative research on this topic, to develop a comprehensive understanding of QoL for this population.Methods: Medline, EMBASE and PsycINFO were systematically searched with keywords relating to HCC, QoL and patient experience. After applying inclusion and exclusion criteria, key findings of included studies were extracted and analysed for themes.Results: Eleven studies were included for thematic analysis, with five themes identified as central to QoL: (1) burden of physical symptoms and treatment side effects;(2) psychological impact and coping strategies; (3) social function and stigma; (4) spiritual wellbeing, sense of self and meaning of illness and (5) pervasive uncertainty. Conclusion:HCC profoundly impacted patients' lives, spanning physical, psychological, social and spiritual QoL domains. While QoL was reduced overall, some features of patient experiences that enhanced QoL were noted. The findings complement data from quantitative studies, helping to build a richer understanding of QoL.hepatocellular carcinoma (one key word preferably), liver neoplasms, palliative care, qualitative research, quality of life | INTRODUCTIONHepatocellular carcinoma (HCC) is the main form of primary liver cancer and one of the most common malignancies worldwide (Bray et al., 2018;McGlynn et al., 2021). Aetiology of HCC varies, but Hepatitis B virus (HBV), Hepatitis C virus (HCV) and high alcohol consumption are all important risk factors (Singal et al., 2020). Liver cirrhosis is a primary risk factor for HCC regardless of underlying cause (Singal et al., 2020). HCC also carries a high mortality rate and is the fourth leading cause of cancer-related deaths (Bray et al., 2018;Singal et al., 2020). Five-year survival rates are globally less than 20%, in part because the absence of symptoms in early stages leads to delayed diagnosis (Laube et al., 2021). By the time of diagnosis, most patients This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.