Effects of Propofol on Traumatic Brain Injury-Induced Insults to the Mouse Blood-Brain Barrier and Its Possible Mechanisms

Project: A - Government Institutionb - National Science and Technology Council

Project Details


Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in individuals under the age of 45 yr in the world. Pathologic conditions associated with head injury are accompanied by endothelial cell dysfunction, leading to increased permeability across the blood-brain barrier (BBB), which might lead to the development of cerebral edema. The edema and its associated complications account for approximately 50% of deaths in patients with TBI. The BBB is present at the level of the brain capillaries and is critical for ion homeostasis in the central nervous system. A lot of studies demonstrate that TBI results in BBB opening after injury, providing further evidence that the cerebral vasculature is functionally and morphologically damaged by TBI. Additionally, it is likely that some of the aspects of cerebral vascular dysfunction due to TBI contribute to the increased sensitivity of the injured brain to secondary hypoxia and hypotension and the increased mortality and morbidity that occurs due to secondary insults after TBI in humans. Patients with severe head injuries are usually managed in the ICU. Sedation is part of the treatment algorithm to prevent secondary brain injury. Propofol is the hypnotic agent of choice in patients with an acute neurological insult. Propofol has additional properties that may be beneficial in the head injured patient including a decrease in cerebral metabolic rate, decrease in intracranial pressure, potentiation of GABAminergic inhibition and inhibition of NMDA glutamate receptors and prevention of lipid peroxidation. The neuroprotective effects of propofol have been investigated in numerous in vivo and in vitro models of cerebral ischemia. However, there are relatively fewer reports on the effects of propofol in traumatic brain injury, especially propofol how to affect the integrity of BBB. Therefore, we undertook this study to determine whether propofol at clinical doses exerts protective effect on BBB in the in vivo and in vitro mouse TBI models. First, we build up an in vitro CECs culture model to mimic the physiological BBB and we substitute for brain edema-induced hypoxia condition with an oxygen glucose deprivation (OGD) method. Various experiments were performed to examine the protective effects and molecular mechanisms of propofol in vitro. Then we fed ICR mice as an in vivo model to investigate the effect of TBI on BBB functions and the protective effect of propofol. We hope these results may display the mechanisms for the TBI-induced BBB integrity disturbance and the protective effects of propofol administration, and then provide potential targets for the therapy of TBI-induced brain edema.
Effective start/end date8/1/107/31/11


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