Increase in blood-brain barrier permeability does not directly induce neuronal death but may accelerate ischemic neuronal damage

• Published in: Experimental Animals Vol. 67; no. 4; pp. 479 - 486
• Main Authors: Suzuki, Yasuhiro, Umemura, Kazuo, Nagai, Nobuo, Sakai, Yusuke, Ohmori, Chiemi, Matano, Yasuki
• Format: Journal Article
• Language: English
• Published: Japan Japanese Association for Laboratory Animal Science 2018; Japan Science and Technology Agency
• Subjects: Acceleration; Animals; Apoptosis; Blood-brain barrier; Blood-Brain Barrier - metabolism; Brain - cytology; Brain - pathology; Brain damage; Brain injury; Brain Ischemia - etiology; Brain Ischemia - pathology; Capillary Permeability - physiology; Carotid artery; Cell death; Cerebral blood flow; Cerebral infarction; Disease Models, Animal; Infarction; Ischemia; ischemic stroke; Male; Membrane permeability; Mice; Mice, Inbred C57BL; Mortality; neuronal death; Neurons - pathology; Occlusion; Original; Permeability; blood-brain barrier; apoptosis; neuronal death; ischemic stroke; permeability
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.18-0038

It is observed that the increase in blood-brain barrier (BBB) permeability (BBBP) is associated with ischemic stroke and thought to trigger neuronal damage and deteriorate ischemic infarction, even though there is no experimental proof. Here, we investigated the effect of BBBP increase on brain damage, using a combination of photochemically-induced thrombotic brain damage (PIT-BD) model, a focal brain ischemic model, and transient bilateral carotid artery occlusion model (CAO, a whole brain ischemic model), in mice. In PIT-BD, BBBP increased in the region surrounding the ischemic damage from 4 h till 24 h with a peak at 8 h. On day 4, the damaged did not expand to the region with BBBP increase in mice with PIT-BD alone or with 30 min CAO at 1 h before PIT-BD, but expanded in mice with 30 min CAO at 3.5 h after PIT-BD. This expansion was paralleled with the increase in the number of apoptotic cells. These findings indicate that increase in BBBP does not cause direct neuronal death, but it facilitates ischemic neuronal loss, which was attributed, at least partially, to acceleration of apoptotic cell death.