Angiogenesis effects of 4-methoxy benzyl alcohol on cerebral ischemia-reperfusion injury via regulation of VEGF-Ang/Tie2 balance.

Abstract

Angiogenesis facilitates the formation of microvascular networks and promotes neurological deficit recovery after cerebral ischemia-reperfusion injury (CIRI). This study investigated the angiogenesis effects of 4-methoxy benzyl alcohol (4-MA) on CIRI. The angiogenesis effects of 4-MA and the potential underlying mechanisms were assessed based on a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and a hind limb ischemic (HLI) mouse model. Immunofluorescence was conducted to detect microvessel density, and Western blotting and polymerase chain reaction were performed to determine the expression of angiogenesis-promoting factors. In addition, we investigated whether the angiogenesis effects of 4-MA caused damage to the blood-brain barrier (BBB). After treatment with 4-MA (20 mg/kg) for 7 days, the neurological deficits recovered and microvessel density in the cerebral cortex increased in the MCAO/R rats. Additionally, 4-MA also regulated the expression of angiogenesis factors, with an increase in vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression and a decrease in angiopoietin 1 (Ang-1), Ang-2, and Tie-2 expression in both MCAO/R rats and HLI mice. Moreover, 4-MA increased the expression of angiogenesis-promoting factors without exacerbating BBB cascade damage in MCAO/R rats. Our results indicated that 4-MA may contribute to the formation of microvascular networks, thus promoting neurological deficit recovery after CIRI.

• Authors: Fangyan He, Chenjing Ma, Jin Feng, Xiufang Li, Shuangli Xia, Qing Lin, Rong Dai
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 99 Issue 12 Pg. 1253-1263 (Dec 2021) ISSN: 1205-7541 [Electronic] Canada
• PMID: 34283928 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inducing Agents
• Angiopoietin-1
• Angiopoietin-2
• Vascular Endothelial Growth Factor A
• Kdr protein, rat
• Receptor, TIE-2
• Tek protein, mouse
• Vascular Endothelial Growth Factor Receptor-2
• Benzyl Alcohol

Topics

• Angiogenesis Inducing Agents
• Angiopoietin-1 (genetics, metabolism)
• Angiopoietin-2 (genetics, metabolism)
• Animals
• Benzyl Alcohol (administration & dosage, pharmacology)
• Blood-Brain Barrier (metabolism)
• Brain Ischemia (drug therapy, genetics, metabolism)
• Disease Models, Animal
• Gene Expression (drug effects, genetics)
• Male
• Mice
• Rats, Sprague-Dawley
• Receptor, TIE-2 (genetics, metabolism)
• Reperfusion Injury (drug therapy, genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)