Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils.
Giuliani. Daniela D; Leone. Sheila S; Mioni. Chiara C; Bazzani. Carla C; Zaffe. Davide D; Botticelli. Annibale R AR; Altavilla. Domenica D; Galantucci. Maria M; Minutoli. Letteria L; Bitto. Alessandra A; Squadrito. Francesco F; Guarini. Salvatore S
Key Findings
- A nanomolar dose of NDP‑α‑MSH (340 µg/kg i.p.) given every 12 h for 11 days reduced hippocampal damage after global ischemia in gerbils.
- The protective effect lasted at least 67 days and was seen even when treatment began 3–18 h after the stroke event.
- Blocking MC4 receptors eliminated the benefit, showing the effect depends on this receptor pathway.
Practical Outcomes
- The study suggests melanocortin peptides could be a long‑lasting neuroprotective agent if given soon after a stroke, with a surprisingly wide treatment window (up to ~18 h). However, the work is in animals, uses injectable dosing, and the peptide isn’t approved for human stroke treatment, so it’s not ready for direct DIY protocols.
Summary
In a gerbil study, a synthetic melanocortin peptide (NDP‑α‑MSH) given by injection soon after a short brain‑blood flow blockage protected brain cells and memory for at least two months, even when treatment started up to about 18 hours later. The protection relied on a specific brain receptor (MC4).
Abstract
Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus. Treatment with a nanomolar dose (340 microg/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h after the ischemic episode, reduced hippocampal damage with improvement in subsequent functional recovery. The protective effect was long-lasting (67 days, at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest treated (18 h) gerbils, some spatial memory deficits were detected. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain ischemia, melanocortins can provide strong and long-lasting protection with a broad therapeutic treatment window, and with involvement of melanocortin MC(4) receptors, 18 h being the approximately time-limit for stroke late treatment to be effective.
Study Information
pubmed
2006
2006-03-24T00:00:00.000Z
10.1016/j.ejphar.2006.03.038