TY - JOUR
T1 - Reduction of neutrophil activity decreases early microvascular injury after subarachnoid haemorrhage
AU - Friedrich, Victor
AU - Flores, Rowena
AU - Muller, Artur
AU - Bi, Weina
AU - Peerschke, Ellinor I.B.
AU - Sehba, Fatima A.
N1 - Funding Information:
We thank Simon Buttrick for careful editing and proof reading of the manuscript. This project was funded by the American Heart Association grant number GRNT4570012 (FAS) and the National Institutes of Health, grant numbers RO1 NS050576 (FAS).
PY - 2011/8/19
Y1 - 2011/8/19
N2 - Background: Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in the structure and function of parenchymal vessels (≤ 100 μm). The role of neutrophils in these changes has not been determined. This study investigates the role of neutrophils in early microvascular changes after SAH. Method: Rats were either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum, which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC), which limits neutrophil activity. SAH was induced by endovascular perforation. Neutrophil infiltration and the integrity of vascular endothelium and basement membrane were assessed immunohistochemically. Vascular collagenase activity was assessed by in situ zymography.Results: Vinblastine and anti-PMN serum reduced post-SAH accumulation of neutrophils in cerebral vessels and in brain parenchyma. PDTC increased the neutrophil accumulation in cerebral vessels and decreased accumulation in brain parenchyma. In addition, each of the three agents decreased vascular collagenase activity and post-SAH loss of vascular endothelial and basement membrane immunostaining.Conclusions: Our results implicate neutrophils in early microvascular injury after SAH and indicate that treatments which reduce neutrophil activity can be beneficial in limiting microvascular injury and increasing survival after SAH.
AB - Background: Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in the structure and function of parenchymal vessels (≤ 100 μm). The role of neutrophils in these changes has not been determined. This study investigates the role of neutrophils in early microvascular changes after SAH. Method: Rats were either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum, which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC), which limits neutrophil activity. SAH was induced by endovascular perforation. Neutrophil infiltration and the integrity of vascular endothelium and basement membrane were assessed immunohistochemically. Vascular collagenase activity was assessed by in situ zymography.Results: Vinblastine and anti-PMN serum reduced post-SAH accumulation of neutrophils in cerebral vessels and in brain parenchyma. PDTC increased the neutrophil accumulation in cerebral vessels and decreased accumulation in brain parenchyma. In addition, each of the three agents decreased vascular collagenase activity and post-SAH loss of vascular endothelial and basement membrane immunostaining.Conclusions: Our results implicate neutrophils in early microvascular injury after SAH and indicate that treatments which reduce neutrophil activity can be beneficial in limiting microvascular injury and increasing survival after SAH.
UR - http://www.scopus.com/inward/record.url?scp=80051791219&partnerID=8YFLogxK
U2 - 10.1186/1742-2094-8-103
DO - 10.1186/1742-2094-8-103
M3 - Article
C2 - 21854561
AN - SCOPUS:80051791219
SN - 1742-2094
VL - 8
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
M1 - 103
ER -