Atorvastatin combined with low-dose dexamethasone for vascular endothelial cell dysfunction induced by chronic subdural hematoma

Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group.Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells.However,atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury.The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone.Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma.The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31,2016(approval No.IRB2016-YX-036).The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31,2018(approval No.IRB2018-088-01).

Cognitive impairment after traumatic brain injury is associated with reduced long-term depression of excitatory postsynaptic potential in the rat hippocampal dentate gyrus

Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.