Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats

Abstract

Chronic subdural hematoma (CSDH) is a neurological disorder with a substantial recurrence rate. Atorvastatin is an effective drug for treating hyperlipidemia and known to improve neurological outcome after intracerebral hemorrhage. Previous studies have reported that atorvastatin treatment promotes hematoma absorption in CSDH, while the underlying mechanisms remain unclear. In this study, we investigated whether the anti-inflammatory effects of atorvastatin mediate absorption of CSDH. 144 male, Wistar rats (6 months old) were randomly divided into the following groups: 1) sham surgery control, 2) treatment: CSDH + atorvastatin, and 3) vehicle control: CSDH + saline. Atorvastatin or saline was orally administered daily for 19 days after CSDH procedure. A T2WI MRI was used to evaluate CSDH volume changes during the time course of the study. Flow cytometry and immunohistochemical staining were used to measure the number of regulatory T cells (Treg). ELISA was used to measure cytokine level in the hematoma border. Neurological function and cognitive outcome were evaluated using Foot-Fault test and Morris Water Maze test, respectively. When compared to saline treatment, atorvastatin treatment accelerated the absorption of CSDH as indicated by decreased hematoma volume in T2WI MRI data on 14th and 21st day after CSDH (P<0.05). Atorvastatin treatment significantly increased the number of Treg in circulation and hematoma border from 3rd to 21st day after CSDH. Atorvastatin treatment significantly decreased the levels of interleukins (IL-6 and IL-8) and tumor necrosis factor-α (TNF-α), but increased IL-10 level in the hematoma border. Atorvastatin treatment also improved neurological function and cognitive outcome compared to vehicle treated group. Atorvastatin induced anti-inflammatory responses and increased Treg in circulation and brain which may contribute to the accelerated CSDH absorption in rats.

Blood-Based Biomarkers for Predictive Diagnosis of Cognitive Impairment in a Pakistani Population

“…Lipid-lowering therapy has been shown to ameliorate asymptomatic intracranial atherosclerosis, which is a risk factor for vascular CI and dementia (Xie et al, 2018 ; Zou et al, 2018 ; Miao et al, 2019 ; Shetty et al, 2019 ). Atorvastatin treatment also improved cognitive outcomes and induced anti-inflammatory response in a rat model for a chronic subdural hematoma and intracerebral hemorrhage (Quan et al, 2019 ).…”

“…There was a negative correlation observed between triglycerides and MMSE scores. Hence lipid-lowering therapy can improve neurological outcome (Quan et al, 2019 ).…”

Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke

“…Meanwhile, more recent studies have focused on the immune response, with an emphasis on lymphocytic infiltration, as they contribute to brain recovery through hematoma resolution, neurogenesis, and axonal regeneration after ICH. Regulatory T cells were shown to mediate anti-inflammatory responses and improve neurological function in a chronic subdural hematoma rat model (Frost et al, 2019;Quan et al, 2019). These studies may provide emerging therapeutic targets for ICH .…”

Atorvastatin Plus Low-Dose Dexamethasone May Be Effective for Leukemia-Related Chronic Subdural Hematoma but Not for Leukemia Encephalopathy: A Report of Three Cases

“…Clinical studies have indicated that atorvastatin, which is a 3hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, can effectively treat CSDH by promoting vessel maturation and inhibiting intracapsular inflammation (15)(16)(17). Furthermore, preliminary findings from a randomized proof-of-concept clinical trial have indicated that atorvastatin plus low-dose dexamethasone treatment was effective in reducing hematoma and neurological symptoms in patients with CSDH (14).…”