Modified Middle Cerebral Artery Occlusion Model Provides Detailed Intraoperative Cerebral Blood Flow Registration and Improves Neurobehavioral Evaluation

The effects of adenosine on regional cerebral blood flow and indexes of the total and perfused microvascular bed were studied after 1 h of middle cerebral artery occlusion in the anesthetized rat. Iodo[14C]antipyrine was used to determine cerebral blood flow. Fluorescein isothiocyanate-dextran was used to study the perfused microvasculature, and an alkaline phosphatase stain was used to identify the total bed. Mean arterial blood pressure was significantly reduced by adenosine. Cerebral blood flow increased significantly by 75%, except in the flow-restricted cortex where flow averaged 28 +/- 15 (SD) ml.min-1.100 g-1 in control and 34 +/- 33 ml.min-1.100 g-1 in adenosine-treated animals. No significant regional structural differences were observed within the microvascular beds of the two groups. The percentage of the microvascular volume perfused increased significantly in all brain regions in the adenosine-treated rats, including the flow-restricted cortex. The percent perfused arteriolar volume in the flow-restricted cortex was 30 +/- 12% in control and 95 +/- 3% in adenosine-treated animals. Similar values for the capillary bed were 22 +/- 10% in control and 54 +/- 3% in adenosine-treated rats. These results indicate a maintenance of flow with a reduction in diffusion distances in the flow-restricted cortex after treatment with adenosine.

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Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00299.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H967-H977 ◽

Cited By ~ 5

Author(s):

Jennifer A. Shearer ◽

Susan J. Coker ◽

Hilary V. O. Carswell

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Platelet Aggregation ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Whole Blood ◽

Artery Occlusion ◽

Cyclooxygenase Inhibitors ◽

Cerebral Artery Occlusion

2-Arachidonoylglycerol (2-AG) is a major modulator of blood flow and platelet aggregation and a potential neuroprotectant. The present study investigated, for the first time, the effects of 2-AG on cerebral blood flow (CBF) in the first critical hours during middle cerebral artery occlusion (MCAO) and on platelet aggregation in rats. Adult male Sprague-Dawley rats ( n = 30) underwent permanent MCAO under isoflurane anesthesia and were randomly assigned to receive either 2-AG (6 mg/kg iv), monoacylglycerol lipase inhibitor JZL-184 (10 mg/kg iv), or vehicle ( n = 6 rats/group) treatment. CBF and cardiovascular responses were measured, by a blinded investigator, for up to 4 h. In separate experiments, platelet aggregation by 2-AG (19–300 µM) was assessed by whole blood aggregometry ( n = 40). 2-AG and JZL-184 significantly increased the severity of the CBF deficit versus vehicle (20.2 ± 8.8% and 22.7 ± 6.4% vs. 56.4 ± 12.1% of pre-MCAO baseline, respectively, P < 0.05) but had no effect on blood pressure or heart rate. While JZL-184 significantly increased the number of thrombi after MCAO, this did not reach significance by 2-AG. 2-AG induced platelet aggregation in rat whole blood in a similar manner to arachidonic acid and was significantly reduced by the cyclooxygenase inhibitors indomethacin and flurbiprofen and the thromboxane receptor antagonist ICI 192,605 ( P < 0.05). This is the first study showing that 2-AG increases the severity of the CBF deficit during MCAO, and further interrogation confirmed 2-AG-induced platelet aggregation in rats. These findings are important because 2-AG had previously been shown to exert neuroprotective actions and therefore force us to reevaluate the circumstances under which 2-AG is beneficial. NEW & NOTEWORTHY 2-Arachidonoylglycerol (2-AG) has neuroprotective properties; however, the present study revealed that 2-AG increases the severity of the cerebral blood flow deficit during middle cerebral artery occlusion in rats. Further interrogation showed that 2-AG induces platelet aggregation in rats. These findings force us to reevaluate the circumstances under which 2-AG is beneficial.

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