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

Abstract

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.

Pre-Treatment with Laminarin Protects Hippocampal CA1 Pyramidal Neurons and Attenuates Reactive Gliosis Following Transient Forebrain Ischemia in Gerbils

“…A number of previous studies have demonstrated that reactive gliosis due to various pathological conditions in the central nervous system increases permeability of the blood-brain barrier [20][21][22]. This can accelerate ischemic neuronal damage [23] and trigger inflammatory responses [24][25][26], which can exacerbate neuronal death [25]. Reactive gliosis commonly occurs following TFI, and in this process, glial cells (astrocytes and microglia) are hypertrophied with a thickened cellular structure [6,7,15].…”

Novel therapeutics for hydrocephalus: Insights from animal models

“…It has been shown that chronic hypoxia could cause older rats to exhibit the characteristics of adult chronic hydrocephalus, including increased ventricular size, slightly increased intracranial pressure, and cognitive deficits in the brain 124 . Besides, free radicals, such as reactive oxygen species and reactive nitrogen species, are also associated with oxidative damage to neurons and other brain cells 125,126 . Oxidative stress induced by hypoxia/ischemia environment involving lipid peroxidation and oxidative and nitrosylative reaction may be one of the mechanisms of brain injury in hydrocephalus.…”

Brain-Derived Microparticles (BDMPs) Contribute to Neuroinflammation and Lactadherin Reduces BDMP Induced Neuroinflammation and Improves Outcome After Stroke

“…Physiological responses after stroke include BBB break down, delayed angiogenesis and neuron death (55). Previous studies have shown that neuronal damage in the central nervous system (CNS) is correlated with blood-brain barrier (BBB) breakdown (56)(57)(58). BBB is important for maintaining stability of the brain microenvironment of brain.…”