BACKGROUND AND PURPOSE: Cerebral hypoxic ischemia (HI) is an important cause of brain injury in the newborn infant. Adenosine is believed to protect against HI brain damage. However, the roles of the different adenosine receptors are unclear, particularly in young animals. We examined the role of adenosine A2A receptors (A2AR) using 7-day-old A2A knockout (A2AR(-/-)) mice in a model of HI. METHODS: HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated with the use of histopathological scoring and measurements of residual brain areas at 5 days, 3 weeks, and 3 months after HI. Behavioral evaluation of brain injury by locomotor activity, rotarod, and beam-walking test was made 3 weeks and 3 months after HI. Cortical cerebral blood flow, assessed by laser-Doppler flowmetry, and rectal temperature were measured during HI. RESULTS: Reduction in cortical cerebral blood flow during HI and rectal temperature did not differ between wild-type (A2AR(+/+)) and knockout mice. In the A2AR(-/-) animals, brain injury was aggravated compared with wild-type mice. The A2AR(-/-) mice subjected to HI displayed increased forward locomotion and impaired rotarod performance in adulthood compared with A2AR(+/+) mice subjected to HI, whereas beam-walking performance was similarly defective in both groups. CONCLUSIONS: These results suggest that, in contrast to the situation in adult animals, A2AR play an important protective role in neonatal HI brain injury.
BACKGROUND AND PURPOSE:Cerebral hypoxic ischemia (HI) is an important cause of brain injury in the newborn infant. Adenosine is believed to protect against HI brain damage. However, the roles of the different adenosine receptors are unclear, particularly in young animals. We examined the role of adenosine A2A receptors (A2AR) using 7-day-old A2A knockout (A2AR(-/-)) mice in a model of HI. METHODS:HI was induced in 7-day-old CD1mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated with the use of histopathological scoring and measurements of residual brain areas at 5 days, 3 weeks, and 3 months after HI. Behavioral evaluation of brain injury by locomotor activity, rotarod, and beam-walking test was made 3 weeks and 3 months after HI. Cortical cerebral blood flow, assessed by laser-Doppler flowmetry, and rectal temperature were measured during HI. RESULTS: Reduction in cortical cerebral blood flow during HI and rectal temperature did not differ between wild-type (A2AR(+/+)) and knockout mice. In the A2AR(-/-) animals, brain injury was aggravated compared with wild-type mice. The A2AR(-/-) mice subjected to HI displayed increased forward locomotion and impaired rotarod performance in adulthood compared with A2AR(+/+) mice subjected to HI, whereas beam-walking performance was similarly defective in both groups. CONCLUSIONS: These results suggest that, in contrast to the situation in adult animals, A2AR play an important protective role in neonatal HI brain injury.
Authors: D Pereira-Figueiredo; R Brito; D S M Araújo; A A Nascimento; E S B Lyra; A M S S Cheibub; A D Pereira Netto; A L M Ventura; R Paes-de-Carvalho; K C Calaza Journal: Purinergic Signal Date: 2020-02-20 Impact factor: 3.765
Authors: Elizabeth A Newell; Jennifer L Exo; Jonathan D Verrier; Travis C Jackson; Delbert G Gillespie; Keri Janesko-Feldman; Patrick M Kochanek; Edwin K Jackson Journal: Brain Res Date: 2014-11-03 Impact factor: 3.252
Authors: Zeng-Jin Yang; Bing Wang; Herman Kwansa; Kerry D Heitmiller; Gina Hong; Erin L Carter; Jessica L Jamrogowicz; Abby C Larson; Lee J Martin; Raymond C Koehler Journal: J Cereb Blood Flow Metab Date: 2013-07-17 Impact factor: 6.200
Authors: Fatima A Sehba; Rowena Flores; Artur Muller; Victor Friedrich; Jiang-Fan Chen; Gavin W Britz; H Richard Winn; Joshua B Bederson Journal: J Neurosurg Date: 2010-10 Impact factor: 5.115