ACTH Protects Brains by Modulating Protein Expression After Ischemic Injury

The Adrenocorticotropic Hormone (ACTH) is a crucial peptide hormone primarily known for its role in the stress response, but it also exhibits significant neuroprotective properties. While its beneficial effects in various brain injury models have been observed, the precise molecular mechanisms by which ACTH exerts these protective actions, particularly through changes in the brain's protein expression profile, remain incompletely understood.

ACTH treatment significantly improved neurological deficit scores by 43% (p<0.001) compared to the control group, indicating substantial functional recovery. Proteomic analysis identified 138 proteins that were significantly altered (p<0.05, with a >1.5-fold change) in the brains of ACTH-treated rats. > The most impactful finding was a 2.8-fold increase in BDNF (Brain-Derived Neurotrophic Factor, a key protein promoting neuronal survival and plasticity) and a 3.1-fold decrease in GFAP (Glial Fibrillary Acidic Protein, a marker of reactive astrogliosis and brain injury) in the ischemic hippocampus of ACTH-treated animals. Furthermore, proteins involved in oxidative stress pathways (e.g., SOD1, GPx1) showed a 25-40% upregulation, while inflammatory markers (e.g., IL-6, TNF-α) were downregulated by 30-55% in the ACTH group, suggesting a broad anti-inflammatory and antioxidant effect.