Background: Therapeutic hypothermia protects the brain in acute ischemic stroke (AIS), but current methods are complex or cause systemic side effects. Stroke induces hepatic gluconeogenesis and splenic immune activation, which exacerbate brain injury via peripheral–central interactions. This study evaluates intraperitoneal cooling infusion (IPCI), a selective hypothermia strategy targeting abdominal organs while maintaining brain and core temperature, to disrupt these injury pathways across liver, spleen and brain. Method: Ninety-six male Sprague Dawley rats underwent 2h middle cerebral artery occlusion followed by reperfusion for 0.5, 3, 6, 24, or 48h, with or without IPCI (4–6 °C saline, initiated 30 min before reperfusion and continued for 30 min after). Outcomes included infarct volume (TTC), neurological scores, hepatic injury markers (AST, ALT, LDH), gluconeogenesis (PCK-1/2), glucose in liver/serum/brain, inflammatory markers (CD68, MPO) in spleen/serum/brain, and cerebral oxidative stress (ROS, MDA, SOD). Result: IPCI markedly reduced infarct volume and neurological deficits. Continuous temperature monitoring confirmed that IPCI selectively lowered liver and spleen temperatures to 32–33 °C without altering brain or core (rectal) temperature, ensuring targeted cooling without systemic hypothermia. Stroke elevated hepatic injury markers (AST, ALT, LDH), PCK-1/2 expression, and liver glucose within 0.5 h, followed by delayed increases in serum and brain glucose; IPCI reversed these changes. Splenic CD68/MPO and corresponding serum and brain levels rose after stroke, indicating peripheral inflammatory activation; IPCI significantly suppressed these elevations. In the brain, IPCI reduced oxidative stress, evidenced by decreased ROS and MDA and restored SOD levels. Conclusion: Selective liver–spleen cooling via IPCI interrupts post-stroke metabolic and inflammatory cascades, reducing hepatic gluconeogenesis, limiting spleen-derived immune activation, and attenuating cerebral oxidative stress. By maintaining normal brain and core temperatures, IPCI avoids the complications of systemic hypothermia while achieving robust neuroprotection. This minimally invasive approach highlights a novel paradigm of targeting peripheral organ–brain crosstalk in stroke. IPCI holds strong translational promise as simple and practical adjunct to reperfusion therapy and may reshape future strategies for neuroprotection in AIS.
Cheng et al. (2026) studied this question.