Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM). ...Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM). Matrix metalloproteinases(MMPs) may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan(CGM) following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups:(1) sham operation group: craniotomy only;(2) lesion(L) group: craniotomy + surgical trauma lesion;(3) lesion + CGM(L + CGM) group: CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2(marker of proliferating neural progenitor cells) and matrix metalloproteinases(MMP2 and MMP9) in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2+/SOX2+ cells and MMP9^+/SOX2^+ cells were seen within the lesion boundary zone in the L + CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.展开更多
The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental p...The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.展开更多
基金supported by grants from the National Science Council of China(NSC 102-2314-B-303-004)the Tzu Chi Medical Mission Project 105-06,Buddhist Tzu Chi Medical Foundation
文摘Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM). Matrix metalloproteinases(MMPs) may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan(CGM) following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups:(1) sham operation group: craniotomy only;(2) lesion(L) group: craniotomy + surgical trauma lesion;(3) lesion + CGM(L + CGM) group: CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2(marker of proliferating neural progenitor cells) and matrix metalloproteinases(MMP2 and MMP9) in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2+/SOX2+ cells and MMP9^+/SOX2^+ cells were seen within the lesion boundary zone in the L + CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.
文摘The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.