DOCUMENT

Headlines 13 a sign of disease they can crawl in via channels that traverse the meningeal layers.” “One of the reasons we’ve had such a lack of effective drugs to date is because of the blood- brain barrier (BBB). It makes getting treatments into the brain really hard. But getting drugs into the border tissues is easy, and now we know there’s a direct connection, it could make treatments such as immunotherapy much more effective.” Scientists are also exploring whether these networks can be used to flush out the proteins that build up in brain cells in Alzheimer's and Parkinson’s — or even prevent the diseases in the first place. “Alzheimer's patients actually show signs of inflammation and altered immune cells within the bone marrow of the skull, so we think there's a lot of interactions going on between the skull and the brain in these conditions.” In the lab at the University of Auckland’s Centre for Brain Research (CBR), Justin has been collecting donations of dura mater and matched brains from Parkinson's and Alzheimer's patients and a few of motor neuron disease, and has just added some neurologically normal control patients. He is supervising PhD student Luca Vinnell to do the hands-on lab work involving immunostaining, RNAscope, and imaging. They will both analyse the results, looking at how cells within the central nervous system communicate with the immune system cells in the brain borders. “Central nervous system cells employ neurotransmitters to control complex brain functions, and immune cells use cytokines to manage inflammation. Our research will identify how unexpected cytokine communication happens between these cells in both normal brains and in Parkinson’s brains. We hope this will pave the way for potential treatments by leveraging the influence of the immune system.” Justin adds: “At the moment, I'm probably the only one in New Zealand interested in studying this dural or skull tissue in depth. There’s an element of future-proofing – I think people will realise the significance of this collection down the track, and it will be there for other researchers to use.” Justin is also drawing on the expertise of CBR heavyweights Professor Michael Dragunow and Professor Maurice Curtis as co-investigators. The project was granted $15,000 in the Neurological Foundation’s last funding round to help purchase materials and equipment. References: Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature 523 , 337-341(2015). Rustenhoven, J., Kipnis, J. Brain borders at the central stage of neuroimmunology. Nature 612 , 417–429 (2022). First Fellow explores skull stem cells to heal brain after concussion Dr Sam McCullough is the Neurological Foundation’s newest First Fellow. The First Fellowship Grant is for an outstanding early career researcher to complete their first post-doctoral fellowship, under close academic mentorship. Sam is based at the University of Auckland’s Centre for Brain Research (CBR) and will be supervised by Dr Justin Rustenhoven as well as Professor Michael Dragunow. His exciting project is exploring the potential of stem cells taken from skull bone marrow to treat mild traumatic brain injuries (mTBIs) which are also known as concussions. He says the project is extremely important for New Zealand’s population, where concussions are exceptionally common, particularly in young adults. Following a concussion, the blood vessels, referred to as the vasculature, in the brain are damaged. Failure of the vessels to fully heal is thought to contribute to some of the distressing long term symptoms that may develop, such as difficulties with memory and changes in personality. Sam is investigating a newly identified subset of cells in the brain, named skull bone marrow stem cells (BMSCs), and whether they can be used to aid vasculature repair following a brain injury. He hopes to determine which factors are involved in the activation and recruitment of these cells from the brain bone marrow in response to blood vessel damage after a concussion. “Characterising these stem cells and accessing their mechanisms of action will further the understanding of our brains cellular response to concussion allowing for the therapeutic enhancement of this repair function,” Sam says. “The development of new therapies is crucial to reduce the severity of long-term effects associated with mTBI and improved patient outcomes – which is particularly important in New Zealand given our high prevalence of concussion. “Together, this research will improve our understanding of concussion and offers hope for future stem cell therapies.” Dr SamMcCullough