Endogenous CDNF affects the hemorrhagic lesion after ICH. A Photograph of representative films demonstrating temporal changes in CDNF protein in the naive striatum and ICH-affected striatum, at 3?h to 7 days post-ICH in SD rats, which were assessed using Western blotting. B Bar graph showing the relative levels of CDNF protein in the striatum of naïve rats and rats at 3?h, 6?h, 24?h, 72?h, and 7 days after ICH. Data were analyzed as repeated measures by one-way ANOVA followed by Bonferroni corrections (?=?4/time point). C Bar graph showing time course of CDNF mRNA levels in hemorrhagic striatum at 3?h to 7 days after ICH in SD rats. Data were analyzed as repeated measures by one-way ANOVA followed by Bonferroni corrections (?=?3/time point). D Representative coronal sections (1?mm thickness) showing brain hemorrhagic areas of WT and Cdnf?/? mice killed 3 days after ICH. E Lesion volume on days 3 (?=?7–8, each group) post-ICH was determined by morphometric measurement. Data were analyzed as two-tailed Student’s t-test. F Volcano plot of gene expression profiles in hemorrhagic striatum collected after collagenase-induced ICH in WT and Cdnf-/- mice, showing distribution of significance [?log10(adjusted P value)] vs. fold change [log2(fold change)] for all genes. The blue dots indicate downregulated genes (fold change???1.5, adjusted P val 0.05), the red dots indicate upregulated genes (fold change 1.5, adjusted P val 0.05), and the black dots indicate genes with no significant change post-ICH. *P??0.05 by multiple comparisons using the Holm-Šidák method. Mean ± SEM is shown. Scale bars: 5?mm. Credit: Cell Death Disease (2023). DOI: 10.1038/s41419-022-05520-2
Intracerebral hemorrhage, and bleeding into the brain tissue, is a devastating neurological condition affecting millions of people annually. It has a high mortality rate, while survivors are affected by long-term neurological deficits. No medication has been found to support brain recovery following hemorrhage.
In an international collaboration, researchers from the Brain Repair laboratory, University of Helsinki, together with their Taiwanese colleagues investigated whether a protein called cerebral dopamine neurotrophic factor (CDNF) has potential as a treatment for brain hemorrhage.
Researchers suggest that cerebral dopamine neurotrophic factor, a protein being currently tested for Parkinson’s disease treatment, also has therapeutic effects and enhances immune cell’s response after brain hemorrhage.
The authors found that the administration of cerebral dopamine neurotrophic factor accelerates hemorrhagic lesion resolution, reduces brain swelling, and improves functional outcomes in an animal model of brain hemorrhage.
“Surprisingly, we found that cerebral dopamine neurotrophic factor acts on immune cells in the bleeding brain, by increasing anti-in?ammatory mediators and suppressing the production of the pro-in?ammatory cytokines that are responsible for cell signaling. This is a significant step towards the treatment of injuries caused by brain hemorrhage, for which we currently have no cure,” says Professor Mikko Airavaara, from University of Helsinki.
Dr. Vassileios Stratoulias from the Brain Repair laboratory comments, “It’s interesting to note that after a bleeding episode, the brain contains a lot of waste and debris. Cerebral dopamine neurotrophic factor encourages immune cells in the brain to consume and remove the waste and debris, which is essential for the brain’s recovery.”
The administration of cerebral dopamine neurotrophic factor also resulted in the alleviation of cell stress in the area that surrounds the hematoma.
Finally, the researchers demonstrated that systemic administration of cerebral dopamine neurotrophic factor promotes scavenging by the brain’s immune cells after brain hemorrhage and has bene?cial effects in an animal model of brain hemorrhage.
The findings are published in the journal Cell Death Disease.
Kuan-Yin Tseng et al, Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage, Cell Death Disease (2023). DOI: 10.1038/s41419-022-05520-2
A new way to remove waste from the brain after hemorrhage (2023, March 16)
retrieved 16 March 2023
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