Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression

TY - JOUR

T1 - Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression

AU - Ilie, A

AU - Ciocan, D

AU - Constantinescu, A O

AU - Zagrean, A-M

AU - Nita, D A

AU - Zagrean, L

AU - Moldovan, M

N1 - Keywords: Animals; Brain; Central Nervous System Agents; Cerebrovascular Circulation; Dimethyl Sulfoxide; Electroencephalography; Ischemic Attack, Transient; Laser-Doppler Flowmetry; Male; Rats; Rats, Wistar; Receptor, Adenosine A1; Synaptic Transmission; Time Factors; Xanthines

PY - 2009

Y1 - 2009

N2 - Following transient global cerebral ischemia (GCI), spontaneous electrocortical activity resumes from the isoelectric line through a sequence of "bursts" of activity alternating with periods of electrical "suppression," commonly referred to as the post-ischemic burst suppression (BS) pattern. Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four-vessel occlusion" model under chloral hydrate anesthesia. Quantification of BS recovery was carried out using BS ratio. During GCI full electrocortical suppression was attained (BS ratio reached 100%). During the following reperfusion the BS ratio returned to 0. The time course of the decay was exponential after 1 and 5-min GCI and bi-exponential after 10-min GCI. The BS recovery was progressively delayed with the duration of ischemia. Administration of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1.25 mg/kg i.p.) accelerated the post-ischemic BS recovery for all GCI durations. Following the 10-min GCI the effect of DPCPX was only apparent on the initial fast decay of the BS ratio. These data suggest that endogenous adenosine release promotes BS patterns during reperfusion following transient cerebral ischemia. Furthermore, the endogenous A1R activation may be the primary underlying cause of post-ischemic BS patterns following brief ischemic episodes. It is likely that synaptic depression by post-ischemic A1R activation functionally disrupts the connectivity within the cortical networks to an extent that promotes BS patterns.

AB - Following transient global cerebral ischemia (GCI), spontaneous electrocortical activity resumes from the isoelectric line through a sequence of "bursts" of activity alternating with periods of electrical "suppression," commonly referred to as the post-ischemic burst suppression (BS) pattern. Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four-vessel occlusion" model under chloral hydrate anesthesia. Quantification of BS recovery was carried out using BS ratio. During GCI full electrocortical suppression was attained (BS ratio reached 100%). During the following reperfusion the BS ratio returned to 0. The time course of the decay was exponential after 1 and 5-min GCI and bi-exponential after 10-min GCI. The BS recovery was progressively delayed with the duration of ischemia. Administration of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1.25 mg/kg i.p.) accelerated the post-ischemic BS recovery for all GCI durations. Following the 10-min GCI the effect of DPCPX was only apparent on the initial fast decay of the BS ratio. These data suggest that endogenous adenosine release promotes BS patterns during reperfusion following transient cerebral ischemia. Furthermore, the endogenous A1R activation may be the primary underlying cause of post-ischemic BS patterns following brief ischemic episodes. It is likely that synaptic depression by post-ischemic A1R activation functionally disrupts the connectivity within the cortical networks to an extent that promotes BS patterns.

U2 - 10.1016/j.neuroscience.2009.01.025

DO - 10.1016/j.neuroscience.2009.01.025

M3 - Journal article

C2 - 19344634

SN - 0306-4522

VL - 159

SP - 1070

EP - 1078

JO - Neuroscience

JF - Neuroscience

IS - 3

ER -