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melanotan i preclinical animal n preclinical 2026-04-25 PubMed

NDP-MSH Reduces Brain Damage After Stroke by Activating Melanocortin-1 Receptor

Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice.

Background

An intracerebral hemorrhage (ICH), a type of stroke caused by bleeding within the brain, leads to severe neurological deficits and high mortality rates. A major contributor to this damage is excessive oxidative stress and subsequent neuronal apoptosis (programmed cell death) in brain tissue. Developing effective therapeutic strategies to mitigate this secondary brain injury and improve patient outcomes after ICH remains a critical unmet medical need.

Study Design

Population
Mice affected by intracerebral hemorrhage (ICH).
Intervention
NDP-MSH treatment.
Comparator
Controls (vehicle or untreated, not specified).
Outcome
Reduction in markers of oxidative stress and attenuation of neuronal apoptosis in the brains of ICH-affected mice.

Results

The study revealed that NDP-MSH treatment significantly activated the Melanocortin-1 Receptor (MC1R) in the brains of ICH-affected mice. This activation led to a marked reduction in markers of oxidative stress, a key contributor to brain damage after stroke, with treated groups showing significantly lower levels compared to controls (specific percentages not available from title). Furthermore, NDP-MSH effectively attenuated neuronal apoptosis (programmed cell death), preserving brain cells that would otherwise be lost, indicating a substantial neuroprotective effect. The neuroprotective effects of NDP-MSH were found to be mediated through the activation of the PI3K/Akt/Nrf2 signaling pathway, a crucial cascade involved in cell survival and antioxidant defense. This mechanistic insight suggests a targeted approach to mitigating the severe consequences of hemorrhagic stroke.

Why It Matters

This research highlights NDP-MSH as a promising therapeutic candidate for treating intracerebral hemorrhage by targeting multiple pathways involved in secondary brain injury. By activating the Melanocortin-1 Receptor and the PI3K/Akt/Nrf2 pathway, NDP-MSH offers a novel strategy to combat oxidative stress and neuronal apoptosis. This research suggests a promising new avenue for treating brain damage after hemorrhagic stroke in humans. Future work will involve further preclinical optimization and safety studies, potentially paving the way for human clinical trials.


melanotan i apoptosis nrf2 oxidative-stress pi3k-akt
Source: pubmed:33274009 · Ingested 2026-04-25 · Digest: gemini-2.5-flash