Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes

Abstract

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.

Acute changes of pro-inflammatory markers and corticosterone in experimental subarachnoid haemorrhage: A prerequisite for severity assessment

“…Injection of blood led to a typical significant increase of ICP as well as a significant decrease of CBF in SAH animals compared to sham. In the animals of the SAH group, the blood injection-induced transient peak response of ICP elicited the well-known cushing reflex [21] (S3 Fig).…”

“…Surgery and recording setup was conducted as previously described [21]. Briefly, anaesthesia was induced in the morning (7:45–8:00 am) using Isoflurane (Isoflurane, Forene, Ludwigshafen, Germany), intravenous fentanyl infusion and local anaesthesia at each skin incision (Ropivacainhydrochlorid, 2mg/ml, Fresenius Kabi, Bad Homburg, Germany) were used as analgesia.…”

“…Six hours after blood injection, the animal was sacrificed in deep anaesthesia by an intravenous (i.v.) injection of highly concentrated potassium chloride (2.5M) (~ 05:00 p.m., range: 04:45 p.m.– 05:54 p.m.) The brain was removed, rinsed with saline for removal of epidurally adherent blood, and SAH was acutely graded according to our modified SAH scale [21]. Pictures were taken for blinded offline confirmation of the acute grading (S1 Fig).…”

Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis

“…Preliminary data on retinal vessel reactivity in patients after SAH using Dynamic Vessel Analyzer (DVA, IMEDOS Systems UG, Jena, German) suggest a characteristic role of NVC in neurological diseases [ 14 , 15 ]. Although NVC manifestation of retinal vessel response to flicker light in humans has been documented before [ 16 , 17 ], the underlying pathophysiology requires further clarification using basic research.…”

Vaskuläre Biomarker der retinalen Gefäßanalyse

“…Verschiedene methodologische Modalitäten der dynamischen retinalen Gefäßanalyse wurden entwickelt und in klinischen Studien an Gesunden und an Patienten mit Augenerkrankungen und systemischen Erkrankungen getestet: [47], Neurochirurgie [64,65], Nephrologie [66], Gynäkologie [46], Sportmedizin [28], Diabetologie [67 -69], Hypertensiologie [54,70] usw. durchgeführt.…”