Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism. Colostrum is the first milk produced by mammals for their young. It plays an important role in protection and development by providing various antibodies, growth factors and nutrients, and has been used for various diseases in many countries. In the present study, we investigated the anti-apoptotic effects of bovine colostrum using organotypic hippocampal slice cultures and an intracerebral hemorrhage animal model. We performed densitometric measurements of propidium iodide uptake, a step-down avoidance task, Nissl staining, and caspase-3 immunohistochemistry. The present results revealed that colostrum treatment significantly suppressed N-methyl-D-aspartic acid-induced neuronal cell death in the rat hippocampus. Moreover, colostrum treatment improved short-term memory by suppressing hemorrhage-induced apoptotic neuronal cell death and decreasing the volume of the lesion induced by intracerebral hemorrhage in the rat hippocampus. These results suggest that colostrum may have a beneficial role in recovering brain function following hemorrhagic stroke by suppressing apoptotic cell death.
Research Highlights
(1) In vitro experiment results confirmed that bovine colostrum can inhibit N-methyl-D-aspartic acid-induced neuronal cell death in the rat hippocampus. (2) In vivo experimental results confirmed that bovine colostrum can inhibit intracerebral hemorrhage-induced neuronal cell death, decrease caspase-3 expression, and reduce the size of intracerebral hemorrhage-induced lesions in the hippocampus, and improve the cognitive function of rats with intracerebral hemorrhage.
INTRODUCTION
Brain injury after intracerebral hemorrhage occurs through multiple mechanisms including direct tissue destruction, the space-occupying effect of hematomas, ischemic damage to adjacent tissue, clot-derived toxic factors, and edema[1,2]. Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism[3]. Apoptosis, the process of programmed cell death, plays an important role in normal development and tissue homeostasis through functions in cell replacement, tissue remodeling, and the removal of damaged cells[4,5]. However, inappropriate or excessive apoptosis is implicated in several types of neurodegenerative disorders, including stroke[3,4,5,6]. Inflammation contributes to secondary brain injury induced by intracerebral hemorrhage. Inflammation is characterized by the accumulation and activation of inflammatory cells and mediators within the hemorrhagic brain[7]. Therefore, it has been suggested that activation and regulation of inflammatory responses in the hemorrhagic brain could be a therapeutic target for intracerebral hemorrhage[8].
Colostrum is the first milk produced by female mammals during the first few days postpartum. It provides various antibodies, growth factors, and nutrients such as proteins, carbohydrates, fats, vitamins and minerals for the neonate. Moreover, colostrum contains many biologically active constituents that play important roles in protection and development[9]. Bovine colostrum has been used for the treatment of various gastrointestinal disorders, intestinal inflammation, respiratory infections, rheumatoid arthritis, and the healing of injured tissues[10,11,12]. Recently, Schuster et al [13] reported that colostrinin, a class of proline-rich polypeptides derived from colostrum, had a protective effect on neuroblastoma cells by reducing fibril formation and cell death induced by beta-amyloid.
As mentioned above, many studies have reported on the beneficial effects of colostrum. However, these reports have mainly focused on its protective effects against various infectious microorganisms, and few studies have investigated the anti-apoptotic effect of colostrum. Therefore, in the present study, we investigated the anti-apoptotic effects of bovine colostrum in organotypic hippocampal slice cultures and in an intracerebral hemorrhage animal model.
