Improved Neuronal Survival of Focal Ischemia After Delipid Extracorporeal Lipoprotein Treatment in Hyperlipidemic Rabbits

Abstract

A delipid extracorporeal lipoprotein filter (DELP) system has been used to treat patients with stroke and has shown favorable prognosis. However, the mechanism for the neuronal functional recovery remains unclear. This study aimed to investigate the neuronal histological assessment, and the levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and oxidized low-density lipoprotein (oxLDL) after ischemic stroke following DELP treatment. Hyperlipidemic rabbits underwent middle cerebral artery occlusion. After 30 min, the animals received an extracorporeal apheresis treatment with a DELP filter. Total cholesterol (TC), triglyceride, and low-density lipoprotein (LDL) of the plasma were measured. The levels of CRP, TNF-α, and oxLDL in brain tissue were also measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining, cresyl violet staining, neuron-specific enolase (NSE) and glial fibrillary acidic protein immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed. DELP apheresis reduced TC and LDL by >30%. The number of neurons at day 7 (P < 0.01) and the integrated optical density of NSE at day 1 (P < 0.05) and day 7 (P < 0.01) were significantly increased in the DELP group. TUNEL-positive cells were significantly decreased (P < 0.05). Astrocytes were moderately activated, and this activation persisted up to 7 days. Gliosis was not found in the DELP group. After treatment, the level of CRP declined at day 1 (P < 0.05); TNF-α and oxLDL declined at day 7 (P < 0.05). DELP apheresis decreased neuronal apoptosis, reduced inflammatory markers and oxidative stress in cerebral ischemia, and improved neuronal survival.

Delipid extracorporeal lipoprotein filter from plasma system: a new intensive lipid lowering therapy for patients with acute ischemic stroke

“…Xue et al found DELP treatment could decrease neuronal apoptosis in experimental stroke models ( 40 ). A retrospective study in venous thrombotic patients with ischemic stroke conducted by Cui et al showed an increase in the proportion of mRS 0 ~ 1 at 90 days ( p = 0.042) in the DELP group compared with NO DELP group ( 41 ).…”

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“…Guojing Liu et al. (1) of Nankai University, Tianjin, China investigated the mechanism of improvement in neuronal survival of focal ischemia after treatment with a delipid extracorporeal lipoprotein filter (DELP) system. Hyperlipidemic rabbits underwent middle cerebral artery occlusion.…”