gms | German Medical Science

Objective: Many patients experience impairments of cerebral autoregulation after subarachnoid hemorrhage (SAH); the extent of these disturbances has been found to correlate with adverse outcome. We previously showed that CO2 reactivity and neurovascular coupling (NVC) are successively lost within the first 24 hours after experimental subarachnoid hemorrhage (SAH). NVC even showed an inverse reaction to neuronal activation. It is, however, unclear if and how pronounced neurovascular reactivity is affected over time. We therefore investigated the neurovascular reactivity of pial and intraparenchymal vessels by in vivo 2-photon microscopy one month after experimental SAH.

Methods: C57BL/6 mice were subjected to SAH (induced by the MCA filament perforation model) or sham surgery. 30 days after hemorrhage induction, cerebral blood flow (CBF) was assessed by laser Doppler fluxmetry following CO2 - challenge (10% pCO2 in 30% O2/ 70% air) and during (continuous or intermittent) forepaw stimulation as a NVC test paradigm. Diameters of pial arteries and intraparenchymal arterioles were quantified at the same time by in vivo two-photon microscopy via a cranial window; for visualization of vessels, FITC dextrane was injected intraarterially.

Results: One month after SAH, pial and parenchymal vessels dilated normally, i.e. approximately 15% of baseline, in response to an elevated CO2 with no difference to sham operated animals. This indicates complete recovery of pCO2-induced vessel reactivity. Neurovascular coupling was still almost completely absent, i.e. vessel diameter did not increase upon forepaw stimulation as compared to a 20% dilatation in sham-operated mice.

Conclusion: These results suggest a differential impairment and recovery of neurovascular function after SAH: CO2 reactivity, absent early on after SAH, recurs within one month after the bleeding while neurovascular coupling, initially intact and subsequently lost at 24 hours after hemorrhage, is still absent. These findings demonstrate for the first time that acute neurovascular dysfunction after SAH lasts for a prolonged period of time and may serve as a link between microcirculatory changes/ early brain injury (EBI) and delayed cerebral ischemia (DCI), two pathophysiological phenomena occurring after SAH that were so far believed not to be directly related.