Hypoxic Preconditioning Reduces Ceramide Formation, TNFα Levels, and TNFR1 Expression in the Rat Brain in Acute Cerebral Ischemia

• Published in: Journal of evolutionary biochemistry and physiology Vol. 61; no. 4; pp. 1209 - 1216
• Main Authors: Gerasimov, P. N., Protopopov, V. A., Bryndina, I. G.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.07.2025; Springer Nature B.V
• Subjects: Animal Physiology; Biochemistry; Biomedical and Life Sciences; Carotid arteries; Carotid artery; Ceramide; Enzymes; Evolutionary Biology; Experimental Papers; Hypoxia; Immunofluorescence; Ischemia; Life Sciences; Neurological diseases; Palmitoyltransferase; Serine palmitoyltransferase; Sphingomyelin phosphodiesterase; Survival; Tumor necrosis factor receptors; Tumor necrosis factor-α; ceramide; TNFα; phospholipids; hypoxic preconditioning; cerebral ischemia; TNFR1
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093025040210

The aim of the work was to study changes in the content of ceramide and key enzymes involved in its biosynthesis, as well as TNFα content and TNFR1 expression levels, in the rat brain under conditions of acute cerebral ischemia (ACI) and hypoxic preconditioning (HP); additionally, we aimed to assess the relationship between these factors and animal survival rates and neurological deficit. The experiments were carried out on 37 male outbred white rats weighing 180–230 g. ACI was induced by irreversible ligation of the left common carotid artery combined with reversible ligation of the right common carotid artery. The animals were divided into three groups: group 1—sham-operated rats (control); group 2—rats exposed to ACI; and group 3—rats exposed to ACI and HP. On day 3 of observation, neurological deficit was assessed using the Garcia scale; changes in the levels of TNFα, TNFR1 expression, ceramide, serine palmitoyltransferase, ceramide synthase, and acid and neutral sphingomyelinases were evaluated by immunofluorescence microscopy. ACI led to increased ceramide production and elevated levels of all the ceramide-synthesizing enzymes in the brain, being also accompanied by higher levels of TNFα and upregulated TNFR1 expression. HP abated these effects, preventing the rise in ceramide, sphingomyelinase, and TNFα levels, as well as in TNFR1 expression, thereby reducing the severity of neurological deficits and improving animal survival rates compared to ACI. Thus, HP demonstrated its efficacy as a method to reduce neurological impairments and increase survival in experimental animals, as well as to partly prevent changes in pro-inflammatory factors and ceramide levels due to suppression of key enzymes involved in its synthesis.