Identification and validation of growth hormone-reactive gene markers in brain tissue during the recovery period of stroke
- Brain Res Bull. 2026 Sep:243:111988. doi: 10.1016/j.brainresbull.2026.111988.
- 1. Department of Rehabilitation Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
- 2. Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: [email protected].
Background: Functional recovery after ischemic stroke is often incomplete, highlighting the need for therapies that enhance neural repair. Growth hormone (GH) has shown potential neuroprotective effects, but its molecular mechanisms in the post-stroke brain remain unclear. This study aimed to identify and validate GH-responsive gene markers and explore their association with functional recovery.
Methods: A middle cerebral artery occlusion (MCAO) rat model was established. RNA Sequencing of peri-infarct tissues was performed on days 7, 14, and 28 after recombinant human GH (rhGH) treatment to identify differentially expressed genes and enriched pathways. Neurological and behavioral assessments were conducted 14 days after rhGH administration. Histological staining was used to evaluate infarct volume, cortical damage, and neuronal Apoptosis. Expression of GH-responsive genes was examined by RT-PCR and Western blot. Oxidative stress and inflammatory markers were measured by ELISA. Pathway specificity was verified using LY294002, a PI3K/Akt/mTOR pathway inhibitor.
Results: rhGH treatment induced a marked transcriptional response, peaking on day 14. rhGH upregulated growth-associated protein 43 (GAP43), insulin-like growth factor-1 (IGF1), brain-derived neurotrophic factor (BDNF), synapsin-1 (SYN1), and vascular endothelial growth factor (VEGFA), while downregulating matrix metalloproteinase-9 (MMP9). rhGH significantly improved neurological outcomes, reduced infarct-related histopathological damage, and inhibited neuronal Apoptosis. It also suppressed oxidative stress and inflammatory responses. Moreover, rhGH activated the PI3K/Akt/mTOR pathway, whereas LY294002 attenuated its neuroprotective effects.
Conclusion: GH promotes neurological recovery after ischemic stroke by reducing inflammation and oxidative stress and activating the PI3K/Akt/mTOR signaling pathway.