Abstract
Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.
Highlights
Subarachnoid hemorrhage (SAH) is a devastating stroke subtype associated with high morbidity and mortality as a result of multifactorial process[1]
Acute brain edema is recognized as a predominant cause of poor clinical outcome after SAH and is primary attributed to blood-brain barrier disruption after ICH[4]
The endothelial cell contraction and disassembly of tight junctions caused increased vascular permeability and consequent formation of brain edema[5], As yet, it has been clearly elucidated that Blood brain barrier (BBB) disruption is a key mechanism of SAH-induced brain injury, there is no effective treatment available against brain edema and BBB disruption
Summary
Subarachnoid hemorrhage (SAH) is a devastating stroke subtype associated with high morbidity and mortality as a result of multifactorial process[1]. Acute brain edema is recognized as a predominant cause of poor clinical outcome after SAH and is primary attributed to blood-brain barrier disruption after ICH[4]. The endothelial cell contraction and disassembly of tight junctions caused increased vascular permeability and consequent formation of brain edema[5], As yet, it has been clearly elucidated that BBB disruption is a key mechanism of SAH-induced brain injury, there is no effective treatment available against brain edema and BBB disruption. Iron has a major role in SAH-induced brain injury. The breakdown of hemoglobin during blood resolution results in iron overload in acute phase of SAH and causes oxidative injury leading to neuronal cell death.
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