A method to evaluate dynamic cerebral pressure-flow relationships in the conscious rat

We present a novel technique to overcome the use of vasoactive agents when studying cerebrovascular dynamics in the conscious rat. Our method of vena cava occlusion to reduce BP was associated with decreased iCBF and no change in iCVR. In contrast, comparable BP falls with intravenous SNP increased iCBF and reduced iCVR. Thus, the dynamic cerebral pressure-flow relationship shows a narrower, less level autoregulatory plateau than conventionally thought. We confirm our method allows repeatable assessment of cerebrovascular dynamics in conscious rats.

Conscious rat PET imaging with soft immobilization for quantitation of brain functions: comprehensive assessment of anesthesia effects on cerebral blood flow and metabolism

Background Animal brain functions evaluated by in vivo imaging under anesthesia can be affected by anesthetic agents, resulting in incorrect assessment of physiological brain function. We therefore performed dynamic positron emission tomography (PET) imaging of conscious rats using recently reported soft immobilization to validate the efficacy of the immobilization for brain function assessments. We also determined the effects of six anesthetic agents—a mixed anesthetic agent (MMB), ketamine + xylazine (KX), chloral hydrate (Chloral), pentobarbital (PTB), propofol (PF), and isoflurane (IFL)—on brain function by comparison with conscious rats. Results The immobilization enabled 45-min dynamic [18F]FDG-PET acquisition with arterial blood sampling using conscious rats without the use of special techniques or invasive surgery. The spatial resolution and quantitativity of [18F]FDG-PET were not significantly lower for conscious rats than for anesthetized rats. While MMB, Chloral, PTB, and PF showed ubiquitous reduction in the cerebral metabolic rates of glucose (CMRglu) in brain regions, KX and IFL showed higher reductions in cerebellum and interbrain, and cerebellum, respectively. Cerebral blood flow (CBF) was reduced by MMB, KX, PTB, and PF; increased by IFL; and unaltered by Chloral. The magnitude of decrease in CMRglu and CBF for MMB were not larger than for other five anesthetic agents, although blood glucose levels and body temperature can be easily affected by MMB. Conclusion The six anesthetic agents induced various effects on CMRglu and CBF. The immobilization technique presented here is a promising tool for noninvasive brain functional imaging using conscious rats to avoid the effects of anesthetic agents.

Electroacupuncture exerts an anti-migraine effect via modulation of the 5-HT7 receptor in the conscious rat

Background: Acupuncture has been recommended as an alternative therapy for migraine. Emerging evidence suggests that the 5-HT7 receptor (5-HT7R) plays a significant facilitatory role in descending modulation in migraine pathophysiology, and that activation of 5-HT7R in the descending pathway is involved in migraine central sensitisation. Objective: To investigate the ability of electroacupuncture (EA) to ameliorate central sensitisation via modulation of 5-HT7R in the descending pain pathways using a rat model of migraine induced by repetitive dural electrical stimulation (DES). Design: 64 male Sprague-Dawley rats were randomly divided into four groups: Normal group; DES group (receiving dural electrical stimulation only); DES+GB20 group (DES model group treated with EA at GB20); and DES+Sham group (DES model group treated with EA at a non-traditional (sham) acupuncture point). The presence of cutaneous allodynia was determined by measuring facial and hind-paw withdrawal latencies to electronic von-Frey. The expression of 5-HT7R in the descending pathways (periaqueductal grey, raphe magnus nucleus, and trigeminal nucleus caudalis) was assessed using immunofluorescence and Western blotting. Results: Facial and hind-paw withdrawal thresholds were significantly increased in the DES+GB20 group compared with the untreated DES group. The expression of 5-HT7R was significantly decreased in the DES+GB20 group compared with the DES group (one-way analysis of variance (ANOVA), P<0.05). No significant differences in behaviour or expression were found between the rats in the DES+Sham group and the untreated DES group (one-way ANOVA, P>0.05). Conclusion: EA at GB20 may ameliorate central sensitisation in migraine by inhibiting the activation of 5-HT7 receptors in the descending pain pathway in a rat model of migraine.