Role of Bevacizumab on Vascular Endothelial Growth Factor in Apolipoprotein E Deficient Mice after Traumatic Brain Injury.

Abstract

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB). Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI and to be overexpressed in the absence of apolipoprotein E (ApoE). Bevacizumab, a VEGF inhibitor, demonstrated neuroprotective activity in several models of TBI. However, the effects of bevacizumab on Apo-E deficient mice are not well studied. The present study aimed to evaluate VEGF expression and the effects of bevacizumab on BBB and neuroinflammation in ApoE-/- mice undergoing TBI. Furthermore, for the first time, this study evaluates the effects of bevacizumab on the long-term consequences of TBI, such as atherosclerosis. The results showed that motor deficits induced by controlled cortical impact (CCI) were accompanied by increased brain edema and VEGF expression. Treatment with bevacizumab significantly improved motor deficits and significantly decreased VEGF levels, as well as brain edema compared to the control group. Furthermore, the results showed that bevacizumab preserves the integrity of the BBB and reduces the neuroinflammation induced by TBI. Regarding the effects of bevacizumab on atherosclerosis, it was observed for the first time that its ability to modulate VEGF in the acute phase of head injury prevents the acceleration of atherosclerosis. Therefore, the present study demonstrates not only the neuroprotective activity of bevacizumab but also its action on the vascular consequences related to TBI.

• Authors: Tiziana Genovese, Daniela Impellizzeri, Ramona D'Amico, Roberta Fusco, Alessio Filippo Peritore, Davide Di Paola, Livia Interdonato, Enrico Gugliandolo, Rosalia Crupi, Rosanna Di Paola, Salvatore Cuzzocrea, Marika Cordaro, Rosalba Siracusa
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 8 (Apr 09 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35456980 (Publication Type: Journal Article)

Chemical References

• Apolipoproteins E
• Vascular Endothelial Growth Factor A
• Bevacizumab

Topics

• Animals
• Apolipoproteins E (metabolism)
• Atherosclerosis (metabolism)
• Bevacizumab (pharmacology, therapeutic use)
• Blood-Brain Barrier (metabolism)
• Brain Edema (drug therapy, etiology)
• Brain Injuries, Traumatic (metabolism)
• Disease Models, Animal
• Mice
• Vascular Endothelial Growth Factor A (metabolism)