Parthenolide is the component of tanacetum parthenium that inhibits nitroglycerin-induced Fos activation: studies in an animal model of migraine.

Tanacetum parthenium (TP) is a member of the Asteracee family long used empirically as a herbal remedy for migraine. So far, however, clinical trials have failed to prove consistently the effectiveness of TP extracts in preventing migraine attacks, probably as a consequence of the uncertainty as regards the active principle. In this study, the biological effects of different TP extracts and purified parthenolide were tested in an animal model of migraine based on the quantification of neuronal activation induced by nitroglycerin. The extract enriched in parthenolide significantly reduced nitroglycerin-induced Fos expression in the nucleus trigeminalis caudalis. Purified parthenolide inhibited nitroglycerin-induced neuronal activation in additional brain nuclei and, significantly, the activity of nuclear factor-kappaB. These findings strongly suggest that parthenolide is the component responsible for the biological activity of TP as regards its antimigraine effect and provide important information for future controlled clinical trials.

Effects of isoflurane on prefrontal acetylcholine release and hypothalamic Fos response in young adult and aged rats.

This experiment investigated the influence of age on prefrontal acetylcholine (ACh) release and Fos response in the hypothalamic paraventricular nucleus and the nucleus tractus solitarius (NTS) of rats following isoflurane anesthesia. It is known that isoflurane decreases acetylcholine release in most brain regions. In the present study, we found that the level of prefrontal acetylcholine was significantly lower in 28-month-old rats (14% of baseline) than in 3-month-old rats (38% of baseline) during 2 h of isoflurane anesthesia (P < 0.05). The old rat group showed significantly greater Fos induction in the paraventricular nucleus compared to the young adult rat group (P < 0.05), indicating that the old rats were subjected to stress. No difference in Fos response was noted in the nucleus tractus solitarius. The old rats displayed a significant increase in feeding behavior during the 3-h recovery period (P < 0.05), but there was no difference in overall acetylcholine levels. Taken together, these findings suggest that isoflurane anesthesia influences old rats more profoundly than young adult rats with regard to reductions in acetylcholine release and stress responses. This may have implications for understanding the development of postoperative delirium in aged patients.

Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system of spontaneously hypertensive rats.

Mineralocorticoid effects in the brain include the control of cardiovascular functions, induction of salt appetite, interaction with the vasoactive neuropeptides arginine vasopressin (AVP) and angiotensin II and development or aggravation of hypertension. In this regard, mineralocorticoids may play a pathogenic role in rats with a genetic form of hypertension (spontaneously hypertensive rats, SHR). Our objective was to compare the response of the hypothalamic vasopressinergic system to mineralocorticoid administration in SHR and control Wistar-Kyoto (WKY) rats. Sixteen-week-old male SHR showing a systolic blood pressure of 190 +/- 5 mm Hg and normotensive WKY rats (130 +/- 5 mm Hg) were treated subcutaneously with oil vehicle or a single 10-mg dose of deoxycorticosterone acetate (DOCA). After 2 h, rats were sacrificed and brains prepared for immunocytochemistry of Fos and vasopressin V1a receptor (V1aR) and for non-isotopic in situ hybridization of AVP mRNA. In the basal state, SHR demonstrated a higher number of AVP mRNA- and V1aR-immunopositive cells in the magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WKY rats. After DOCA injection, SHR responded with a significant increase in both parameters with respect to vehicle-injected SHR. In WKY rats, DOCA was without effect on AVP mRNA although it increased the number of V1aR-positive cells. Changes in the number of Fos-positive nuclei were measured in the PVN, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a circumventricular region showing anatomical connections with the PVN. In vehicle-injected rats, the PVN of SHR showed a higher number of Fos-positive nuclei than in WKY rats, whereas after DOCA treatment, a significant increment occurred in the OVLT but not in the PVN or MnPO of the SHR group only. These data suggest that the enhanced response of the vasopressinergic system to mineralocorticoids may contribute to the abnormal blood pressure of SHR.

Kynurenic acid enhances electroacupuncture analgesia in normal and carrageenan-injected rats.

The interaction between electroacupuncture (EA) and an intrathecally administered wide-spectrum excitatory amino acid (EAA) receptor(s) antagonist, kynurenic acid (KYNA) on carrageenan-induced thermal hyperalgesia and spinal Fos expression was investigated. Intrathecal (i.t.) injection of 0.1, 1, 10, and 100 nmol KYNA markedly and dose-dependently increased the latency of paw withdrawal (PWL) of the carrageenan-injected paw. While the PWLs of the non-injected and normal saline (NS)-injected paws were not obviously affected by application of KYNA at the doses tested. Intrathecal injection of 0.1 nmol KYNA significantly potentiated the anti-nociception induced by EA stimulation of contralateral 'Zu-San-Li' and 'Kun-Lun' acupoints either in the carrageenan- or NS-injected rats. Three hours after intraplantar (i.pl.) injection of carrageenan, the number of Fos-like immunoreactive (Fos-LI) neurons was significantly increased in all layers of ipsilateral spinal cord at L(4)-L(5) with the higher density in laminae I-II and V-VI. Intrathecally pre-administered KYNA (10 nmol) significantly reduced the total number of carrageenan-induced Fos-LI neurons with more apparent reduction in laminae I-II and IV-V. Pre-coapplication of 10 nmol KYNA and EA of bilateral 'Zu-San-Li' and 'Kun-Lun' acupoints, the numbers of carrageenan-induced Fos-LI neurons in laminae I-II and V-VI further reduced. The level of Fos expression in the spinal cord induced by carrageenan was significantly lower compared with that of i.t. injection of KYNA or EA alone. These results demonstrated that EAA receptor(s) antagonist could enhance EA-induced anti-nociception and anti-hyperalgesia.