Graft ischemia post cell transplantation to the brain: Glucose deprivation as the primary driver of rapid cell death.

Replacing cells lost during the progression of neurodegenerative disorders holds potential as a therapeutic strategy. Unfortunately, the majority of cells die post-transplantation, which creates logistical and biological challenges for cell therapy approaches. The cause of cell death is likely to be multifactorial in nature but has previously been correlated with hypoxia in the graft core.

Cryogel microcarriers loaded with glial cell line-derived neurotrophic factor enhance the engraftment of primary dopaminergic neurons in a rat model of Parkinson's disease.

Cryogel microcarriers made of poly(ethylene glycol) diacrylate and 3-sulfopropyl acrylate have the potential to act as delivery vehicles for long-term retention of neurotrophic factors (NTFs) in the brain. In addition, they can potentially enhance stem cell-derived dopaminergic (DAergic) cell replacement strategies for Parkinson's disease (PD), by addressing the limitations of variable survival and poor differentiation of the transplanted precursors due to neurotrophic deprivation post-transplantation in the brain. In this context, to develop a proof-of-concept, the aim of this study was to determine the efficacy of glial cell line-derived NTF (GDNF)-loaded cryogel microcarriers by assessing their impact on the survival of, and reinnervation by, primary DAergic grafts after intra-striatal delivery in Parkinsonian rat brains.

Cryogel microcarriers for sustained local delivery of growth factors to the brain.

Neurotrophic growth factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) have been considered as potential therapeutic candidates for neurodegenerative disorders due to their important role in modulating the growth and survival of neurons. However, clinical translation remains elusive, as their large size hinders translocation across the blood-brain barrier (BBB), and their short half-life in vivo necessitates repeated administrations. Local delivery to the brain offers a potential route to the target site but requires a suitable drug-delivery system capable of releasing these proteins in a controlled and sustained manner.

Injectable local drug delivery systems for glioblastoma: a systematic review and -analysis of progress to date.

Glioblastoma (GBM) is an aggressive malignant cancer associated with bleak prognosis and high mortality. The current standard of care for GBM is maximum surgical resection plus radiotherapy and temozolomide (TMZ) chemotherapy. The blood brain barrier (BBB) remains the main obstacle for chemotherapy and severely limits the choice of therapeutic agents.

Policy changes are needed to further reduce perioperative opioid use.

Opioid prescriptions in the perioperative setting are a known risk factor for long-term opioid use and misuse. Recent initiatives in the United States to address the issue have focused on judicious prescribing patterns and quality measurement to minimize opioid dispensing. However, policy gaps have limited the effectiveness of current interventions.