Effects of Atorvastatin on Pathological Changes in Brain Tissue and Plasma MMP-9 in Rats with Intracerebral Hemorrhage

Abstract

To explore the effects of atorvastatin on hydrocephalus, neurocyte apoptosis, and the level of plasma matrix metalloproteinase-9 (MMP-9) after intracerebral hemorrhage (ICH) in rats. A rat model of ICH was established by intracerebral injection of collagenase. The brain water content was determined by the wet/dry weight ratio, ultrastructural changes in brain tissue were observed by electron microscopy, and the level of plasma MMP-9 was quantified by ELISA. Atorvastatin showed significant effects in reducing the brain water content, blocking neuron apoptosis, and decreasing plasma MMP-9 in rats with ICH. There was a positive linear correlation between plasma MMP-9 and the brain water content. Atorvastatin can significantly relieve brain edema, decrease the brain injury caused by MMP-9 and protect neurons in rats with ICH.

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

“…In animal studies, statins showed less neuronal tissue loss and inflammation; increased cell proliferation, angiogenesis, and synaptogenesis in the perihemorrhagic zone with better functional outcomes (85–87). Statins’ neuroprotective actions may be explained by their ability to induce expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) (88) to reduce activated microglia, MMP-9 (89), and cytokine-mediated inflammation (less TNF-α and higher interleukin-10 levels) (90, 91). Statins also reduce BBB dysfunction, edema, tissue loss, and improve CBF in the perihemorrhagic zone (92, 93).…”

Cholesterol: Its Regulation and Role in Central Nervous System Disorders

“…The use of CSI, however, has been shown to increase the risk of bleeding after ischemic stroke, irrespective of plasma cholesterol concentration. Studies show no clear positive effects for CSI on cerebral hemorrhage, although atorvastatin has been shown to significantly relieve brain edema, to decrease the brain injury caused by matrix metalloproteinase-9, and to protect neurons in rats with intracerebral hemorrhage [151]. …”

Atorvastatin Decreases Bone Loss, Inflammation and Oxidative Stress in Experimental Periodontitis

“…Atorvastatin also decreased COX-2 expression within peripheral blood monocytes in patients with acute myocardial infarction [4] and increased IL-10 levels in a dose-dependent manner [5]. Atorvastatin has also been used to inhibit metalloproteinases [6], [7], osteoclastogenesis and bone destruction, and the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) [8].…”