Summary: A peptide administered via nasal drops may help improve recovery following ischemic stroke.
Source: University of Gothenburg.
Faster and better recovery after stroke may be the result of a newly discovered treatment strategy that created new nerve synapses in the brain–a key factor for learning. A study at Sahlgrenska Academy showed improved ability to use the affected paw in mice that received the treatment.
“More nerve sprouts and connections between nerve cells are created so that the remaining cells can take over functions that the dead cells once had,” says Marcela Pekna, associate professor at the Institute of Neuroscience and Physiology at Sahlgrenska Academy.
The focus is on a molecule called C3a peptide, which is produced naturally in the body and even more so with certain medical conditions. In this case, it was administered to laboratory animals through nasal drops.
Of a total of 28 mice with stroke, half received C3a peptide and half a placebo. The treated mice recovered much better.
“Mice have pretty good ability to recover after a stroke, even without treatment, but with C3a they got better much faster and were able to use the affected paw to a higher degree. And they remained better even four weeks after we finished the treatment,” says Anna Stokowska, first author of the study and postdoctoral researcher at Sahlgrenska Academy.
The results from the behavioral analysis were linked to what happened in the brains of the mice, in which treatment with C3a led to what many now consider to be more important for the recovery of function than generation of new nerve cells, namely the creation of new synapses between the cells.
“Say a stroke kills ten million brain cells. Newly created cells equal less than one percent of those that died, and how much can that help? The formation of new nerve synapses is what allows a person to learn, for example, to speak or use her hands and legs again,” says Marcela Pekna. Still a long way to go
As C3a is inactivated if given orally or intravenously, the researchers used nasal drops. The C3a peptide is also extremely expensive to produce and would need to be replaced by a smaller, cheaper molecule with similar properties.
Marcela Pekna and her research team hope that, in the future, this treatment strategy can be applied clinically in humans. The fact that, in the study, C3a began to be given first a week after onset opens for opportunities to help many people.
“In principle, all stroke patients could receive the treatment. Compare that with removing the blood clot, which must be done within the first few hours. Most people arrive at the hospital too late for that treatment. We believe that a combination of this treatment and the correct type of rehabilitation can help patients improve even faster. It might also be possible to treat other illnesses than stroke, such as brain damage after traffic accidents. But that remains to be seen; there is still a long way to go,” Pekna says.
About this neurology research article
Source: Marcela Pekna – University of Gothenburg Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Full open access research for “Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia] ” by Anna Stokowska, Alison L. Atkins, Javier Morán, Tulen Pekny, Linda Bulmer, Michaela C. Pascoe, Scott R. Barnum, Rick A. Wetsel, Jonas A. Nilsson, Mike Dragunow, Marcela Pekna in Brain. Published online December 12 2016 doi:10.1093/brain/aww314
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]University of Gothenburg. “New Discovery May Improve Recovery After Stroke.” NeuroscienceNews. NeuroscienceNews, 4 December 2016. <https://neurosciencenews.com/stroke-recovery-c3a-5744/>.[/cbtab][cbtab title=”APA”]University of Gothenburg. (2016, December 4). New Discovery May Improve Recovery After Stroke. NeuroscienceNews. Retrieved December 4, 2016 from https://neurosciencenews.com/stroke-recovery-c3a-5744/[/cbtab][cbtab title=”Chicago”]University of Gothenburg. “New Discovery May Improve Recovery After Stroke.” https://neurosciencenews.com/stroke-recovery-c3a-5744/ (accessed December 4, 2016).[/cbtab][/cbtabs]
Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia
Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a–C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.
“Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia] ” by Anna Stokowska, Alison L. Atkins, Javier Morán, Tulen Pekny, Linda Bulmer, Michaela C. Pascoe, Scott R. Barnum, Rick A. Wetsel, Jonas A. Nilsson, Mike Dragunow, Marcela Pekna in Brain. Published online December 12 2016 doi:10.1093/brain/aww314