gms | German Medical Science

Objective: The early phase after subarachnoid hemorrhage (SAH) is characterized by significant microcirculatory dysfunction. Microarteriolar constriction and spasms of the cerebral microcirculation (microvasospasm, MVS) have previously been demonstrated in patients as well as after experimental SAH and seem to contribute to microcirculatory deficits and, thus, posthemorrhagic brain damage. MVS pathophysiology has not yet been completely elucidated. Pericytes regulate cerebral perfusion as part of the neurovascular unit and have been described to cause capillary constriction after ischemic stroke; their role after SAH is unknown. We hypothesized that pericytes contribute to MVS after SAH. Therefore, we investigated their role in early microcirculatory dysfunction after experimental SAH using in-vivo 2-photon microscopy to directly assess the cerebral microcirculation.

Methods: In NG2⁺ reporter mice, fluorescent perivascular cells (pericytes) were imaged and plasma was stained by Tetramethylrodamine. After baseline imaging of the pial and parenchymal cerebral microcirculation with 2-photon microscopy (2-PM), animals underwent SAH induction (MCA filament perforation model, n=10), or sham surgery (n=6). 3 hours after SAH induction, 2-PM imaging was repeated. Perivascular NG2⁺ cells (pericytes) were then assessed with regard to the location of microarteriolar spasm formation/ constriction. In a second set of experiments, pericytes were immunohistochemically evaluated by PDGFR staining 3 and 24h after SAH (n=8 per time point) or sham surgery (n=5 per time point).

Results: No pericyte migration or loss was detected in the acute phase of SAH in cortex, hippocampus, or striatum at 3 or 24h after SAH (3h: cortex: SAH 26.9 ±8.9 NG2⁺/PDGFR⁺ cells per ROI, sham 24.5 ±9.9, p=0.7, hippocampus: p=0.4, striatum p=0.5; 24h: cortex: p=0.7, hippocampus: p=0.2, striatum p=0.4). Pericytes did not colocalize with the microarteriolar spasms or constriction (diameter at/ distal to pericyte: 100.2 ±8.2%/ 92.8 ±8.6% of proximal baseline, p=0.9 vs. proximal, p=0.1 vs. distal diameter).

Conclusion: Pericyte constriction does not contribute to the formation of microvascular contractions/microvasospasm in the acute phase after SAH. The current results suggest that the microcirculatory dysfunction after SAH is not relevantly mediated by pericytes. The pathophysiology of early posthemorrhagic microcirculatory disturbances therefore seem to differ from changes observed after ischemic stroke.