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Reduced Response in Cortical Penetrating Artery but Sustained Response in Cortical Surface Artery to Whisker Stimulation in Chronic Hypoxia Mice
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Introduction: We reported massive parenchymal vasodilation in chronic hypoxia mice using a two-photon laser scan microscopy (2P) (1), and reduced neurovascular coupling (NVC) responses but sustained CO2 responses using a laser Doppler flowmetry (LDF) (2,3). We here measure diameter changes of cortical surface and penetrating arteries of somatosensory cortex triggered by a single whisker vibration using 2P in the chronic hypoxia mice.
Aims: The present study aims to elucidate whether two cortical vascular systems, surface and penetrating arteries, are identical or different in response to somatosensory neuronal stimulation in chronic hypoxia mice.
Methods: We used Tie2-GFP transgenic mice (N=6, 7-11 weeks) of which vascular endothelium had GFP for measuring cortical surface vessels. We used intraperitoneal Sulforhodamine 101 for labeling blood plasma for measuring cortical penetrating vessels. All mice were fixed by chronic closed cranial window over the somatosensory cortex one week before experiment (4). Before (day 0) and on days 7, 14 and 21 after chronic keeping in the 8-9% O2 chamber, dynamic spatiotemporal images of cortical arteries to single whisker vibration (10Hz, 5sec) were measured in awake condition. We used confocal microscopy for cortical surface arteries and 2P for cortical penetrating arteries at 100, 200, 300 and 400 µm depths. We analyzed images to assess dynamic changes of diameter of each cortical artery (5). CBF responses at the somatosensory cortex were also assessed using LDF in the same mice.
Results: Diameters of cortical surface arteries increased to whisker stimulation by approximately 10% throughout hypoxia duration lengths. On the other hand, diameters of cortical penetrating arteries revealed to decrease as prolonged hypoxia duration, i.e. d0 (15%), d7 (10%), d14 (9-7%) and d21 (7-5%). The LDF responses were also reduced along hypoxia duration, i.e. d0(20%), d7(15%), d14(9-12%) and d21(5-9%).
Discussion: The results suggest that our previous observation of the reduced NVC response by LDF in chronic hypoxia resulted from a reduced response in diameter change of cortical penetrating arteries. Combining with anothor previous observation by LDF, i.e. sustained response to CO2 in chronic hypoxia mice, it is suggested that the cortical penetrating artery in chronic hypoxia revealed reduced response only to NVC but not to CO2 during chronic hypoxia.
Conclusion: Chronic hypoxia induced reduction in NVC response only in cortical penetrating artery but not in cortical surface artery. This discrepancy between two cortical vascular systems suggests different role in supplying blood flow to brain tissues. Different response to NVC and CO2 in the cortical penetrating arteries implies essential part of NVC response.
References:
(1) Yoshihara K, et al. 357-63, Adv Exp Med Biol 765: 2013.
(2) Kanno I, et al. 507.19, SFN, Washington DC, 2011.
(3) Takuwa H, et al, JCBFM (in press) 2013.
(4) Tomita Y, et al. 858-867, JCBFM 25: 2005.
(5) Sekiguchi Y, et al. Adv Exp Med Biol (in press) 2013.
Reduced Response in Cortical Penetrating Artery but Sustained Response in Cortical Surface Artery to Whisker Stimulation in Chronic Hypoxia Mice
