gms | German Medical Science

Objective: Metabolic demand increases with neuronal activity; adequate supply is then ensured by neurovascular coupling (NVC), adapting cerebral blood flow accordingly. Impairment of NVC was recently reported in the context of clinical and experimental aneurysmal SAH and is thought to correlate with both disease severity and outcome. Voltage-Gated Ca2+-Channels (VGCCs) are key regulators in vasomotor tone. In the present study, we investigate the role of VGCCs in the context of NVC using a non-contact retinal vessel analysis in wildtype (WT) and Cav2.3-deficient (KO) mice.

Methods: Wildtype (WT) and Ca_v2.3-deficient mice (KO) were dark-adapted overnight. Anesthesia was performed by intraperitoneal injection and unilateral application of a mydriaticum achieved pupillary dilatation.An adapted prototype of a non-contact retinal vessel analyzer (RCrodent, Imedos Sytems UG) was used to assess retinal vessel diameter. Dynamic vessel analysis (DVA) using flicker light impulses allowed quantification of vessel reactivity (NVC) as characterized by a change in vessel diameter. The following parameters were calculated: area under curve (AUC) during flicker, mean maximal arterial and venous dilatation (mMAD & mMVD) and constriction (mMAC & mMVC) in response to flicker (%), time until maximal dilation (tMAD & tMVD) and constriction (tMAC & tMVC) in (s).

Results: A total of 57 retinal scans was conducted in 42 male mice (WT n=28, KO n=14, 12-15 weeks old, 25-31 g). Assessment of murine retinal arteries was technically feasible only in 15 animals whereas venous reaction to flicker light was observed in all animals. VGCC-depleted mice were characterized by attenuated functionality of NVC. AUC in artery responses was significantly reduced in Ca_v2.3 deficient mice: AUC_art-KO-6.2 (-11 - -4) %*s vs. AUC_art-WT0.3 (-1.9 – 11.8) %*s, (p = 0.04) and the venous mean maximal dilation (mMVD) was significantly lower: mMVD_KO0.4 (0.1 – 0.8) % vs. mMVD_WT1.0 (0.6 – 1.7) %, (p = 0.046). A trend towards attenuated AUC in veins was also observed in KO vs.WT (p=0.132). Comparable results were observed in tMAD, mMAC, tMAC, tMVD, mMVC, tMVC.

Conclusion: To the best of our knowledge, this is the first study using a novel, non-contact analysis technique to document impairment of NVC in VGCC-deficient mice. Modulation of Cav2.3/R-type-Ca2+-channels may contribute to the pathophysiological changes of NVC in general and may be considered as a novel therapeutic target for vasomotor related ischemic complications as in the context of SAH.