Reduction of neutrophil activity decreases early microvascular injury after subarachnoid haemorrhage

Abstract

BackgroundSubarachnoid 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 SAHMethodRats 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.ResultsVinblastine 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.ConclusionsOur 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.

Interleukin-1&bgr; Increases Release of Endothelin-1 and Tumor Necrosis Factor as Well as Reactive Oxygen Species by Peripheral Leukocytes During Experimental Subarachnoid Hemorrhage

“…Examination of leukocyte migration in the acute and early phases following SAH [16] revealed that this process is less expressed after hemorrhage than during cerebral hypoxia [33][34][35]. Only neutrophils and monocytes were found in the brain parenchyma after SAH, with practically no T lymphocytes.…”

Mechanisms of microthrombi formation after experimental subarachnoid hemorrhage

“…Our histological studies on a pre-chiasmatic injection SAH model showed microthromboemboli are abundant in brain parenchyma (Sabri et al, 2011a,b,c). Sehba and colleagues' recent studies demonstrate the involvement of platelet aggregation and neutrophil infiltration of the observed microvascular injury in the brain parenchyma in the vascular perforation model (Sehba et al, 2005;Friedrich et al, 2011).…”

Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain

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