Abstract
Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.
Highlights
Cerebral ischemia, known as stroke, is a clinical common and refractory cerebrovascular disease that seriously harms human health
Recombinant tissue plasminogen activator (t-PA) is the only therapy approved by the Food and Drug Administration (FDA) in the United States for the treatment of acute ischemic stroke, but its drawback is that its application is limited by the narrow therapeutic window (Sahota and Savitz, 2011)
The pharmacological effect of Danhong injection (DHI) occurs in a dose-dependent manner
Summary
Known as stroke, is a clinical common and refractory cerebrovascular disease that seriously harms human health. There are approximately 15 million new stroke patients worldwide each year, resulting in death of about 6 million people from the disease and making it a major cause of disability and death (Moskowitz et al, 2010; Eltzschig and Eckle, 2011). The subsequent reperfusion after the restoration of blood supply can aggravate further damage of brain tissues, resulting in more severe neurological damage and brain dysfunction, called cerebral ischemia-reperfusion injury (CIRI). Recombinant tissue plasminogen activator (t-PA) is the only therapy approved by the Food and Drug Administration (FDA) in the United States for the treatment of acute ischemic stroke, but its drawback is that its application is limited by the narrow therapeutic window (Sahota and Savitz, 2011). There is an urgent need to develop additional effective drugs for the treatment of CIRI
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