Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats

Abstract

Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult rats received 2 h of middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. Treadmill activity was then initiated 24 h after reperfusion for PostE. The severity of the brain damage was determined by infarct volume, apoptotic cell death, and neurological deficit at one and three days after reperfusion. We measured gluconeogenesis including oxaloacetate (OAA), phosphoenolpyruvate (PEP), pyruvic acid, lactate, ROS, and glucose via ELISA, as well as the location and expression of the key enzyme phosphoenolpyruvate carboxykinase (PCK)‐1/2 via immunofluorescence. We also determined upstream pathways including forkhead transcription factor (FoxO1), p‐FoxO1, 3‐kinase (PI3K)/Akt, and p‐PI3K/Akt via Western blot. Additionally, the cytoplasmic expression of p‐FoxO1 was detected by immunofluorescence. Compared to non‐exercise control, PostE (*p < .05) decreased brain infarct volumes, neurological deficits, and cell death at one and three days. PostE groups (*p < .05) saw increases in OAA and decreases in PEP, pyruvic acid, lactate, ROS, glucose levels, and tissue PCKs expression on both days. PCK‐1/2 expressions were also significantly (*p < .05) suppressed by the exercise setting. Additionally, phosphorylated PI3K, AKT, and FoxO1 protein expression were significantly induced by PostE at one and three days (*p < .05). In this study, PostE reduced brain injury after stroke, in association with activated PI3K/AKT/FoxO1 signaling, and inhibited gluconeogenesis. These results suggest the involvement of FoxO1 regulation of gluconeogenesis underlying post‐stroke neuroprotection.

Cognitive‐exercise dual‐task promotes cognitive function recovery in chronic cerebral ischemia male rats through regulating PI3K/Akt signaling pathway via inhibition of EphrinA3/EphA4

“…In our current study, we analyzed provides new evidence that CEDT is an effective rehabilitation intervention strategy for cognitive impairment after CCI. In addition to this, there are studies that have found sex differences in certain behaviors of rats with cognitive impairment, and such differences may be revealed in the specific response or degree of response to various training protocols (Li et al, 2022;Li, Geng, et al, 2023). Some studies have suggested that the reason for the sex difference may be that estrogen regulates neurotransmitter interactions (Ancelin & Ritchie, 2005), affects metabolism and antioxidants, reduces ischemic damage (Brinton, 2008), and lowers inflammatory responses (Straub, 2007), among others.…”

Optimal rehabilitation strategies for early postacute stroke recovery: An ongoing inquiry

“…Furthermore, it upregulated pro-apoptotic proteins (e.g., Caspase-3), inducing cell apoptosis, while downregulating neurovascular remodeling proteins [e.g., synaptophysin (SYP)][ 11 12 13 14 ]; moreover, very early exercise inhibited hypoxia inducible factor-1α (HIF-1α) degradation and promoted incomplete gluconeogenesis, resulting in exacerbated lactic acidosis and oxidative stress injury. [ 15 16 ] It also amplified endoplasmic reticulum stress and activated the CCAAT-enhancer binding protein (C/EBP)-homologous protein (CHOP) and Caspase-12 mediated apoptosis pathway, further aggravating brain injury. [ 17 ]…”