Improvement in cerebral blood flow and metabolism following subarachnoid hemorrhage in response to prophylactic administration of the hydroxyl radical scavenger, AVS, (+/-)-N,N'-propylenedinicotinamide: a positron emission tomography study in rats.
OBJECTIVE
The hydroxyl radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) has been shown to ameliorate the occurrence of vasospasm following experimental subarachnoid hemorrhage (SAH) and to reduce the incidence of delayed ischemic neurological deficits (DINDs) in patients with SAH. The authors investigated whether prophylactic administration of AVS could improve cerebral blood flow (CBF) and cerebral glucose utilization (CGU) following SAH in rats.


METHODS
Anesthetized rats were subjected to intracisternal injection of blood (SAH group) or saline (control group). Either AVS (1 mg/kg/min) or saline (vehicle group) was continuously injected into the rat femoral vein. Forty-eight hours later, positron emission tomography scanning was used with the tracers 15O-H2O and 18F-2-fluoro-D-glucose to analyze quantitatively CBF and CGU, respectively, in the frontoparietal and occipital regions (12 regions of interest/group). In SAH rats receiving only vehicle, CBF decreased significantly (p < 0.05, Tukey's test) and CGU tended to decrease, compared with values obtained in control (non-SAH) rats receiving vehicle. In rats that were subjected to SAH, administration of AVS significantly (p < 0.05, Tukey's test) improved CBF and CGU in both the frontoparietal and occipital regions compared with administration of vehicle alone.


CONCLUSIONS
Prophylactic administration of AVS improves CBF and CGU in the rat brain subjected to SAH, and can be a good pharmacological treatment for the prevention of DINDs following SAH.
Yamamoto
S
S
Department of Neurosurgery, Hamamatsu University School of Medicine, Japan. seijiy@hama-med.ac.jp
Teng
W
W
Nishizawa
S
S
Kakiuchi
T
T
Tsukada
H
H
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D014055:Tomography, Emission-Computed; D020301:Vasospasm, Intracranial / Q000503:physiopathology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D009536:Niacinamide; D005947:Glucose; C042625:nicaraven