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Background: Traumatic brain injury (TBI) causes substantial mortality and morbidity globally. Current treatments only alleviate symptoms and do not halt secondary injury progression., Objectives: Evaluate the neuroprotective potential of Acorus calamus Linn. (AC) in a Drosophila melanogaster model of high-impact TBI., Methods: Fruit flies (Drosophila melanogaster) of the Oregon R + strain were administered hydroalcoholic extracts of Acorus calamus Linn. (HAEAC) at concentrations of 25 and 50 µg/mL, 24 h and continuously for 72 h, respectively, following TBI induction. Mortality rate, locomotor function, neurotransmitter levels, and oxidative stress markers were assessed at 24 and 72 h post-injury as outcomemeasures., Results: AC significantly reduced post-TBI mortality and improved locomotor function in a dose-dependent manner. Additionally, AC increased acetylcholinesterase, gamma-aminobutyric acid, serotonin, and dopamine levels while reducing glutamate. It also boosted antioxidant activity (superoxide dismutase, glutathione, and catalase) and lowered markers of oxidative damage (malondialdehyde, nitrite)., Conclusions: AC mitigated behavioral deficits, oxidative damage, and neurotransmitter imbalance in fruit flies after TBI. These findings indicate AC may be more effective than individual drugs for TBI therapy. Further research into its neuroprotective phytochemicals is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The goal of this research study was to see how plant extracts of Acorus calamus Linn. and Cordia dichotoma G. Forst. overcome scopolamine-induced Alzheimer's type dementia in mice by activating the cholinergic system, anti-oxidant and protection of neuronal death in the brain (hippocampus region). Scopolamine (1 mg/kg i.p.) reduced mice's routine in behavioral parameters such as Morris Water Maze (MWM), Elevated Plus Maze (EPM), and also the locomotor activity. It also decreases antioxidant levels such as Reduced glutathione (GSH) and also Superoxide dismutase (SOD) but also increases the level of Acetylcholinesterase enzyme (AChE) in brain. Assessment of various behavioral, and biochemical parameters (AChE, SOD, GSH, and Nitrite level) were compared with each group. Acorus calamus (hydro-alcoholic 1:1) 600 mg/kg p.o. and the combination (Acorus calamus 600 mg/kg p.o. + Cordia dichotoma 750 mg/kg p.o.) group showed significant results as compared to Cordia dichotoma 750 mg/kg p.o.in behavioral as well as in biochemical parameters. Histological studies showed significant neuroprotection in the Acorus calamus-treated group and the combination-treated groups. In the future, the Acorus calamus and the combination are possibly helpful in the treatment of various cognitive disorders or it may be valuable to investigate the pharmacological potential of such plant extracts during the treatment of neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Orexin A and B, a recently identified pair of neuropeptides, are produced in perikarya located in the lateral and perifornical hypothalamus (LH and PFH). Immunoreactive fibers from these neurons innervate several nuclei in the hypothalamus. Orexin A and orexin B stimulate feeding when administered intracerebroventricularly to rats. To identify the specific sites of orexin action, orexin A and B were microinjected into a number of hypothalamic and extrahypothalamic sites in rats. Orexin A was found to enhance food intake when injected into four hypothalamic sites, the paraventricular nucleus (PVN), the dorsomedial nucleus (DMN), LH and the perifornical area, but was ineffective in the arcuate nucleus (ARC), the ventromedial nucleus (VMN), and the preoptic area (POA) as well as the central nucleus of the amygdala (CeA) and nucleus of the tractus solitarius (NTS). Orexin B was not effective at any site tested. These findings demonstrate that orexin A receptive sites for stimulation of food intake exist primarily in a narrow band of neural tissue within the hypothalamus that is known to be involved in control of energy homeostasis.

Electrolytic lesions placed in the ventromedial hypothalamus (VMH) of rats induce instant hyperphagia and excessive weight gain. Since neuropeptide Y (NPY) is a potent hypothalamic orexigenic signal, and leptin secreted by adipocytes regulates NPY output, we tested the hypothesis that altered NPYergic-leptin signaling may underlie hyperphagia in VMH-lesioned rats. VMH-lesioned rats exhibiting hyperphagia and excessive weight gain in a time-related fashion were sacrificed on days 2, 7, and 21 post-surgery. Quite unexpectedly, NPY concentrations in the hypothalamic paraventricular nucleus (PVN), a major site of NPY release for stimulation of feeding, and in other sites, such as the dorsomedial nucleus, lateral hypothalamic area and median eminence-arcuate nucleus decreased, with the earliest diminution occurring on day 2 in the PVN only. In vitro basal and K+-evoked NPY release from the PVN of VMH-lesioned rats was significantly lower than that of controls. Analysis of hypothalamic NPY gene expression showed that although the daily decrease in NPY mRNA from 0800 to 2200 h occurred as in control rats, NPY mRNA concentrations were markedly reduced at these times in the hypothalami of VMH-lesioned rats. Leptin synthesis in adipocytes as indicated by leptin mRNA levels was also profoundly altered in VMH-lesioned rats. The daily pattern of increase in adipocyte leptin mRNA at 2200 h from 0800 h seen in controls was abolished, higher levels of leptin gene expression at 2200 h were maintained at 0800 h. The pattern of increase in serum leptin and insulin levels diverged in VMH-lesioned rats. Serum insulin concentration increased to maximal on day 2 and remained at that level on day 21-post-lesion; serum leptin levels on the other hand, increased slowly in a time-related fashion during this period. These results demonstrate that hyperphagia and excessive weight gain in VMH-lesioned rats are associated with an overall decrease in hypothalamic NPY and augmented leptin signaling to the hypothalamus. The divergent time course of increases in serum leptin and insulin levels suggest independent mechanisms responsible for their augmented secretion, and neither these hormones nor VMH lesions altered the daily rhythm in NPY gene expression. These observations underscore the existence of an independent mechanism controlling the daily rhythm in hypothalamic NPY gene expression and suggest that leptin feedback action requires an intact VMH., (Copyright 1999 Elsevier Science B.V.)

Recent pharmacological and morphological studies have raised the likelihood of a regulatory link between the neuropeptide Y (NPY) and beta-endorphin (beta-END) networks in the hypothalamus. To evaluate this link we have examined the effects of NPY administration on the in vivo release of beta-END by push-pull perfusion of the basal hypothalamus. Results showed that centrally injected NPY stimulated the in vivo release of beta-END. This effect was evident only in the absence of testicular steroids since NPY failed to alter beta-END release in intact rats. These data suggest that the well-documented effects of NPY such as inhibition of pituitary gonadotropin release in gonadectomized rats and stimulation of feeding may be mediated, in part, by stimulation of beta-END.

Injection of neuropeptide Y (NPY) into the cerebroventricular system of the rat results in a robust feeding response. In this study, we observed that NPY injection into the fourth ventricle augmented feeding and Fos-like immunoreactivity (FLI) in the paraventricular nucleus (PVN) and in other neighboring nuclei in the forebrain previously implicated in stimulation of feeding. Since the rostral transport of NPY in cerebrospinal fluid after injection into the fourth ventricle is unlikely and the topography of FLI as well as feeding behavior seen in this study are similar to those observed previously after NPY injection into the lateral cerebroventricle, these findings are in accord with the view that feeding induced by NPY injection into the fourth ventricle may also be mediated by NPY receptive elements in the forebrain.

We evaluated the role of neuropeptide Y (NPY), a potent endogenous orexigenic signal, in the ventromedial hypothalamic (VMH) lesion-induced hyperphagia in rats. To produce hyperphagia and excessive weight gain, adult female rats received bilateral electrolytic or sham lesions in the VMH. Concurrently, a permanent intracerebroventricular cannula was implanted in the third ventricle of the brain. After a recovery period, these rats were passively immunized against NPY to evaluate the role of endogenous NPY on hyperphagia. The results showed that intraventricular administration of NPY antibodies abolished the hyperphagia in VMH-lesioned rats. These revelations are in agreement with the notion that altered hypothalamic NPY release or action may underlie the hyperphagia and excessive weight gain seen in response to structural damage in the VMH.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals. These results demonstrate how the relationships between Il-1 beta measured in ECF and the conditions of measurement appear to be integral parts of a whole intracerebral system: cytokine concentrations appear to be inextricably bound to intrahypothalamic conditions created by the sampling device presence and frequency of use.

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that appears to be an integral component of the bidirectional signalling between the immune and central nervous systems. It is produced in the hypothalamus and has been shown to inhibit the hypothalamo-pituitary-gonadal axis and to activate the hypothalamo-pituitary-adrenal axis. IL-1 beta is reported to up-regulate the tachykinin, substance P (SP), in the peripheral nervous system. We have recently observed that members of the hypothalamic tachykinin family including SP, neurokinin A (NKA) and two N-terminal extended forms of NKA (neuropeptides kappa and gamma), inhibit hypothalamic LHRH and pituitary LH release and stimulate adrenal corticosterone secretion. The similarity in the endocrine effects of the tachykinins and the cytokine prompted us to test the hypothesis that IL-1 beta may stimulate the hypothalamic tachykinins, which would then mediate the neuroendocrine effects of IL-1 beta. First, the effects of IL-1 beta on the in vitro release of NKA-like immunoreactivity (NKA-li) from the hypothalamus was examined. Addition of 10 nM IL-1 beta significantly increased NKA-li release from the hypothalami of castrated rats, but not from the hypothalami of intact rats. To identify the site of IL-1 beta action, the effects of intraventricular IL-1 beta (100 ng) on NKA-li levels in various hypothalamic sites of intact and castrated rats were examined. The results showed that IL-1 beta increased NKA-li selectively in the median eminence (ME) and arcuate nucleus (ARC) of castrated rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies were undertaken to determine whether nitric oxide (NO) is involved in induction of the prolactin surge on proestrus and in that induced by ovarian steroids in ovariectomized (ovx) rats, by using inhibitors of NO synthase, the enzyme that generates NO. Two week-ovariectomized rats were treated either with estradiol benzoate (EB, 30 micrograms/rat, s.c.) alone, or with EB and 2 days later with progesterone (P, 2 mg/rat, s.c.) to evoke a prolactin surge in the afternoon. Injections of the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (40 mg/kg, s.c.) at 10.000, 12.00, and 14.00 h completely suppressed the steroid-induced prolactin surge in the afternoon. Similarly, another NO synthase inhibitor, Nw-nitro-L-arginine (100 mg/kg, s.c.), injected at 1000, 1200, and 1400 h on proestrus suppressed prolactin and luteinizing hormone (LH) surges, but failed to alter the daily increase of corticosterone. These studies confirm our earlier report and show that NO is involved in the complex processes that initiate the afternoon prolactin and LH surges of proestrus.

Neuropeptide Y is the most potent orexigenic signal known. To test the hypothesis that NPY is a physiological messenger molecule for normal food intake in rats, we studied the effects of passive immunization against endogenous NPY on cumulative daily food intake in non-fasted spontaneously feeding rats. The results show that continuous central infusion of NPY antibodies markedly suppressed the nighttime and the cumulative 24 h food intake in a dose-dependent fashion. These results support the hypothesis that NPY may be a physiological signal involved in the stimulation of ingestive behavior in rats.

Recent evidence suggests that a decrease in the inhibitory opioid influence is a necessary hypothalamic neural event in the preovulatory and ovarian steroid-induced luteinizing hormone (LH) surge. Whether shifts in ovarian steroidal milieu disrupts this neural event is not known. Therefore, the effects of short-term (3 days) and long-term (13 or 17 days) estradiol 17 beta (E2) exposure on spontaneous, naloxone (NAL) and progesterone (P)-induced LH surges were assessed in ovariectomized (ovx) rats. Two weeks after ovariectomy, rats received subcutaneous Silastic capsules filled with crystalline E2. In rats exposed to E2 for 3 days and infused with saline intravenously between 11.00-14.00 h, plasma LH rose significantly at 17.00 h. NAL infusion between 11.00-14.00 h in these rats to decrease the inhibitory opioid influence, advanced both the onset of LH rise and amplified the secretion of LH in the afternoon. Continuation of E2 exposure for 13 days produced no deleterious effects on either the spontaneous or NAL-induced augmentation in LH responses. However, uninterrupted E2 exposure for 17 days abolished the spontaneous afternoon LH rise and drastically diminished the ability of NAL to advance and amplify the LH response. In the next experiment, we evaluated the effect of P injection (2 mg/rat) at 11.00 h on the afternoon LH release in rats similarly exposed to E2 for either 3 or 17 days. In rats exposed to E2 for 3 days, the P-induced LH release was significantly greater than that observed after saline or NAL infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent studies show that neuropeptide Y (NPY) is widely distributed in the hypothalamus and that it stimulates luteinizing hormone-releasing hormone (LHRH) release from the medial basal hypothalamus (MBH) of male and female rats. The neuroendocrine factors that regulate NPY neurosecretion in two sexes are not well understood. We have previously observed that orchidectomy (orch) in male rats decreased and testosterone (T) replacement increased NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC) and ventromedial nucleus (VMN) and the KCl-evoked in vitro release of NPY from the MBH was likewise decreased after orch and restored by testosterone replacement. Now we report that these NPY responses are different in female rats following removal of the ovaries. Ovariectomy (ovx) decreased NPY concentrations in the ARC and VMN and not in the ME. Estrogen replacement restored NPY concentrations in the ARC and VMN, however, in the ME NPY concentration decreased significantly. Further, the KCl-evoked NPY release in vitro from either the MBH or ME of intact and ovx rats was similar. In an additional concurrent comparative study in male and female rats, we observed that of the 6 microdissected hypothalamic sites, NPY levels were approximately 50% less in the ME of intact females than in those of intact male rats. Again, in male rats there was a significant decrease in NPY levels in the ME, ARC and VMN after orch, whereas in female rats, NPY levels in the ARC and VMN, but not in the ME decreased after ovx.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of castration on the concentration of luteinizing hormone releasing hormone (LHRH) in the anterior pituitary (PIT) was studied in freely-behaving male rats using a push-pull cannula for sampling. In over 70 perfusions of the PIT of rats sampled before and at multiple days after castration there was no consistent change detected in the overall amount, secretory pulse amplitude or frequency or the LHRH signal reaching the PIT.

The degenerative responses of luteinizing hormone-releasing hormone (LHRH)-containing neurons within the mediobasal hypothalamus (MBH) after knife cut lesions (FC) made in the frontal plane of the retrochiasmatic hypothalamus include a reduced number of LHRH-immunoreactive (ir) nerve terminals in the median eminence, reduction in LHRH content of the MBH and growth of novel irLHRH-containing neural processes into FC scar tissue. We have now investigated basal and secretogogue-evoked LHRH release in vitro from the preoptic area-MBH (POA-MBH) of adult male rats at 10 or 60 days after FC. Basal LHRH release rate (P less than 0.05) and total (P less than 0.01) amount released 60 days after FC were reduced when compared to control (CONT) hypothalami, but not shams. A 30 min pulse of naloxone (NAL, 1 mg/ml) stimulated greater than 2-fold relative increase in LHRH release for all groups; however, the total amount of LHRH released by FC hypothalami was less (P less than 0.05) than that of CONT, but not sham POA-MBHs. Although exposure to elevated KCl significantly increased (P less than 0.01) LHRH release for all 3 groups, the FC secretory response was less than that of both CONT (P less than 0.05) and sham (P less than 0.01) groups. In the second experiment single POA-MBH were perifused at 10 days (sham and FC) or 60 days (CONT, sham and FC) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropeptide Y (NPY) is localized in several hypothalamic sites which are implicated in the control of hypothalamic luteinizing hormone-releasing hormone (LHRH) and pituitary luteinizing hormone (LH) release. We have observed previously that in young rats castration decreases and testosterone (T) replacement restores NPY levels in selected hypothalamic sites. However, in aged male rats, NPY levels were decreased in all hypothalamic sites studied. Since testicular function is diminished in aged rats, we reasoned that decreased T feedback may be responsible for the reduction of NPY in the hypothalamus. Therefore, we compared the effects of castration and T-replacement on NPY levels in microdissected hypothalamic sites of 2.5-month- (young) and 15-month-old (aged) male rats. Serum LH and T levels were markedly reduced in aged as compared to those observed in young rats. In association with the decreased hormone levels, NPY levels were significantly reduced in each of the 7 hypothalamic sites of aged as compared to young rats. Further, in young rats, castration reduced and T-replacement prevented the castration-induced depletion in only 3 sites, viz. the ventromedial hypothalamic nucleus (VMN), arcuate nucleus (ARC) and median eminence (ME). In contrast, castration in aged rats reduced NPY levels not only in the VMN as in young rats, but also in the medial preoptic area (MPOA) and dorsomedial nucleus (DMN). However, the marked reduction in the ME and ARC NPY levels of young rats following castration was not observed in the ME and ARC of aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of sustained-release implants of morphine (M) and/or testosterone (T) on serum gonadotropin levels and norepinephrine (NE) and serotonin (5-HT) metabolism in brain regions were examined. While 4 days of M or 5 mm [corrected] T treatment were without significant effect, the combination dramatically decreased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Castration increased NE content of the mediobasal hypothalamus (MBH), and although M, 5 mm [corrected] T, or their combination significantly reduced NE levels in the MBH, they remained elevated compared to intact or 30 mm [corrected] T-treated rats. Further, in the MBH no differences in normetanephrine (NME) levels, nor in NME:NE ratios, nor 5-HT metabolism were evident. In the preoptic area-anterior hypothalamus, NE or 5-HT metabolism were not altered by castration and M and/or T. These results show that M and T interact to suppress LH and FSH release in the apparent absence of any appreciable effect on hypothalamic monoamines.

Recent studies show that bilateral neural transections (NT) at the level of dorsal tegmentum in the mesencephalon significantly increase food intake and decrease latency to onset of feeding behavior in response to neuropeptide Y (NPY). The increased responsiveness to NPY may be due to denervation-induced hypersensitivity to NPY in hypothalamic sites that mediate feeding behavior in rats. To test this hypothesis we have studied the effect of NT on NPY concentrations in 7 neural sites of male rats. Two weeks after NT, NPY levels in 3 hypothalamic nuclei--suprachiasmatic nucleus, arcuate nucleus and ventromedial hypothalamus--were not altered by NT thereby suggesting that NPY innervations in these nuclei may be derived mainly from NPY perikarya in the ARC and elsewhere in the diencephalon. On the other hand, NPY concentrations were markedly decreased (50-60%) in the medial preoptic area, paraventricular nucleus, median eminence and dorsomedial nucleus indicating that a substantial number of neurons in the brainstem, which show coexistence of NPY and adrenergic transmitters, project into these 4 diencephalic nuclei. These findings indicate that NPY-containing neurons in the brainstem may project into selected hypothalamic sites and the reduction in the NT rats of NPY levels, especially in the paraventricular nucleus, may be responsible for the reported increase in sensitivity of the NPY-induced feeding response.

The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.