Evidence for a predominant intrinsic sympathetic control of cerebral blood flow alterations in an animal model of cerebral arteriovenous malformation.

In terms of neurogenic cerebral blood flow (CBF) control, the activity of the sympathetic nervous system (SNS) has a regulating effect. The impact of a manipulation of both the peripheral (via the perivascular sympathetic net) and central components (via the intracortical noradrenergic terminals originating from the locus coeruleus) on CBF-and especially on hyperperfusion syndromes-is unclear. To test the specific patterns following such alterations, cortical oxygen saturation (rSO2), regional CBF (rCBF), and cortical interstitial norepinephrine (NE) concentrations were measured. Twelve weeks after either the creation of an extracranial AV fistula or sham operation, 80 male Sprague-Dawley rats underwent one of the following procedures: (1) no SNS manipulation, (2) peripheral SNS inhibition via bilateral sympathectomy, (3) central SNS inhibition via the neurotoxin DSP-4, or (4) complete SNS inhibition. Norepinephrine concentrations were lowest after complete inhibition (NE [nmol]: pre, 1.8 ± 1.2; post, 2.4 ± 1.8) and highest following peripheral inhibition (NE [nmol]: pre, 3.6 ± 1.9; post, 6.6 ± 4.4). Following fistula occlusion, rCBF (laser Doppler unit [LDU]) and rSO2 (%SO2) increases were highest after complete inhibition (pre: 204 ± 14 LDU, 34 ± 3%SO2; post: 228 ± 18 LDU, 39 ± 3%SO2) and lowest after peripheral inhibition (pre: 221 ± 18 LDU, 41 ± 2%SO2; post: 226 ± 14 LDU, 47 ± 2%SO2). Thus, a complete inhibition down-regulates SNS activity and provokes a cortical hyperperfusion condition. With this, the hitherto unknown predominant role of the intrinsic component could be demonstrated for the first time in vivo.