Inhibition of Indoleamine 2,3-Dioxygenase Exerts Antidepressant-like Effects through Distinct Pathways in Prelimbic and Infralimbic Cortices in Rats under Intracerebroventricular Injection with Streptozotocin.

The application of intracerebroventricular injection of streptozotocin (ICV-STZ) is considered a useful animal model to mimic the onset and progression of sporadic Alzheimer's disease (sAD). In rodents, on day 7 of the experiment, the animals exhibit depression-like behaviors. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn), is closely related to depression and AD. The present study aimed to investigate the pathophysiological mechanisms of preliminary depression-like behaviors in ICV-STZ rats in two distinct cerebral regions of the medial prefrontal cortex, the prelimbic cortex (PrL) and infralimbic cortex (IL), both presumably involved in AD progression in this model, with a focus on IDO-related Kyn pathways. The results showed an increased Kyn/Trp ratio in both the PrL and IL of ICV-STZ rats, but, intriguingly, abnormalities in downstream metabolic pathways were different, being associated with distinct biological effects. In the PrL, the neuroprotective branch of the Kyn pathway was attenuated, as evidenced by a decrease in the kynurenic acid (KA) level and Kyn aminotransferase II (KAT II) expression, accompanied by astrocyte alterations, such as the decrease in glial fibrillary acidic protein (GFAP)-positive cells and increase in morphological damage. In the IL, the neurotoxicogenic branch of the Kyn pathway was enhanced, as evidenced by an increase in the 3-hydroxy-kynurenine (3-HK) level and kynurenine 3-monooxygenase (KMO) expression paralleled by the overactivation of microglia, reflected by an increase in ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and cytokines with morphological alterations. Synaptic plasticity was attenuated in both subregions. Additionally, microinjection of the selective IDO inhibitor 1-Methyl-DL-tryptophan (1-MT) in the PrL or IL alleviated depression-like behaviors by reversing these different abnormalities in the PrL and IL. These results suggest that the antidepressant-like effects linked to Trp metabolism changes induced by 1-MT in the PrL and IL occur through different pathways, specifically by enhancing the neuroprotective branch in the PrL and attenuating the neurotoxicogenic branch in the IL, involving distinct glial cells.

Intracerebroventricular injection of spexin stimulates the hypothalamic-pituitary-testicular axis and increases the secretion of male reproductive hormones in rats.

BACKGROUND: Male reproductive functions are regulated in the hypothalamic-pituitary-gonadal (HPG) axis. Any problem in this axis would lead to the deterioration of reproductive functions. The present study aimed to investigate the effects of intracerebroventricular (icv) Spexin (SPX) infusion on the HPG axis in detail. METHODS: 40 Wistar albino rats were divided into four groups: control, sham, SPX 30 nmol and SPX 100 nmol (n=10). 30 nmol/1 µl/hour SPX was administered icv to the rats in the SPX 30 nmol group for 7 days, while rats in the SPX 100 nmol group were administered 100 nmol/1 µl/hour SPX. On the 7th day, the rats were decapitated, blood and tissue samples were collected. Serum LH, FSH and testosterone levels were determined with the ELISA method, GnRH mRNA expression level was determined in hypothalamus with the RT-PCR method. Seminiferous tubule diameter and epithelial thickness were determined with the hematoxylin-eosin staining method. RESULTS: SPX infusion was increased GnRH mRNA expression in the hypothalamus tissue independent of the dose (p<0.05). Serum LH, FSH and testosterone levels in the SPX groups were increased when compared to the control and sham groups independent of the dose (p <0.05). Histological analysis revealed that SPX infusion did not lead to any changes in seminiferous epithelial thickness, while the tubule diameter increased in the SPX groups (p<0.05). CONCLUSION: The study findings demonstrated that icv SPX infusion stimulated the HPG axis and increased the secretion of male reproductive hormones.

Impacts of Central Administration of the Novel Peptide, LEAP-2, in Different Food Intake Models in Conscious Rats.

Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.

Valine administration in the hypothalamus alters the brain and plasma metabolome in rainbow trout.

Central administration of valine has been shown to cause hyperphagia in fish. Although mechanistic target of rapamycin (mTOR) is involved in this response, the contributions to feed intake of central and peripheral metabolite changes due to excess valine are unknown. Here, we investigated whether intracerebroventricular injection of valine modulates central and peripheral metabolite profiles and may provide insights into feeding response in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were administered an intracerebroventricular injection of valine (10 µg·µL-1 at 1 µL·100·g-1 body wt), and the metabolite profile in plasma, hypothalamus, and rest of the brain (composing of telencephalon, optic tectum, cerebellum, and medulla oblongata) was carried out by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. Valine administration led to a spatially distinct metabolite profile at 1 h postinjection in the brain: enrichment of amino acid metabolism and energy production pathways in the rest of the brain but not in hypothalamus. This suggests a role for extrahypothalamic input in the regulation of feed intake. Also, there was enrichment of several amino acids, including tyrosine, proline, valine, phenylalanine, and methionine, in plasma in response to valine. Changes in liver transcript abundance and protein expression reflect an increased metabolic capacity, including energy production from glucose and fatty acids, and a lower protein kinase B (Akt) phosphorylation in the valine group. Altogether, valine intracerebroventricular administration affects central and peripheral metabolism in rainbow trout, and we propose a role for the altered metabolite profile in modulating the feeding response to this branched-chain amino acid.NEW & NOTEWORTHY Valine causes hyperphagia in fish when it is centrally administered; however, the exact mechanisms are far from clear. We tested how intracerebroventricular injection of valine in rainbow trout affected the brain and plasma metabolome. The metabolite changes in response to valine were more evident in the rest of the brain compared with the hypothalamus. Furthermore, we demonstrated for the first time that central valine administration affects peripheral metabolism in rainbow trout.

The Pattern of GH Action in the Mouse Brain.

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain.

Effect of intracerebroventricular (ICV) injection of adrenomedullin and its interaction with NPY and CCK pathways on food intake regulation in neonatal layer-type chicks.

Adrenomedullin has various physiological roles including appetite regulation. The objective of present study was to determine the effects of ICV injection of adrenomedullin and its interaction with NPY and CCK receptors on food intake regulation. In experiment 1, chickens received ICV injection of saline and adrenomedullin (1, 2, and 3 nmol). In experiment 2, birds injected with saline, B5063 (NPY1 receptor antagonist, 1.25 µg), adrenomedullin (3 nmol) and co-injection of B5063+adrenomedullin. Experiments 3 to 5 were similar to experiment 2 and only SF22 (NPY2 receptor antagonist, 1.25 µg), SML0891 (NPY5 receptor antagonist, 1.25 µg) and CCK4 (1 nmol) were injected instead of B5063. In experiment 6, ICV injection of saline and CCK8s (0.125, 0.25, and 0.5 nmol) were done. In experiment 7, chickens injected with saline, CCK8s (0.125 nmol), adrenomedullin (3 nmol) and co-injection of CCK8s+adrenomedullin. After ICV injection, birds were returned to their individual cages immediately and cumulative food intake was measured at 30, 60, and 120 min after injection. Adrenomedullin (2 and 3 nmol) decreased food intake compared to control group (P < 0.05). Coinjection of B5063+adrenomedullin amplified hypophagic effect of adrenomedullin (P < 0.05). The ICV injection of the CCK8s (0.25 and 0.5 nmol) reduced food intake (P < 0.05). Co-injection of the CCK8s+adrenomedullin significantly potentiated adrenomedullin-induced hypophagia (P < 0.05). Administration of the SF22, SML0891 and CCK4 had no effect on the anorexigenic response evoked by adrenomedullin (P > 0.05). These results suggested that the hypophagic effect of the adrenomedullin is mediated by NPY1 and CCK8s receptors. However, our novel results should form the basis for future experiments.

Protocol for inducing severe Scn2a insufficiency in mice by intracerebroventricular antisense oligonucleotide injection.

SCN2A loss-of-function variants cause a range of neurodevelopmental disorders. Here, we present a protocol to induce severe Scn2a insufficiency in mice. We describe steps for intracerebroventricular (ICV) antisense oligonucleotide (ASO) injection that causes a selective downregulation of Scn2a and ASO-mediated mRNA degradation. We then detail procedures for qPCR and western blot protocol to measure Scn2a mRNA and protein. This protocol can be used as a mouse model for behavioral and in vivo two-photon Ca2+ imaging.

CSF amino acid profiles in ICV-streptozotocin-induced sporadic Alzheimer's disease in male Wistar rat: a metabolomics and systems biology perspective.

Alzheimer's disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular-streptozotocin (ICV-STZ) in an AD-like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg-1) by ICV (2.5 µL into each ventricle for 5 min on each side). In the second week after receiving ICV-STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD-like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV-STZ-treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression.

Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis.

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 µg), kisspeptin + astressin 2B (1 µg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

PURPOSE: Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. METHODS: A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS: The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. CONCLUSIONS: Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

Ommaya reservoir use in pediatric ALL and NHL: a review at St. Jude Children's Research Hospital.

PURPOSE: The intraventricular route of chemotherapy administration, via an Ommaya Reservoir (OmR) improves drug distribution in the central nervous system (CNS) compared to the more commonly used intrathecal administration. We retrospectively reviewed our experience with intraventricular chemotherapy, focused on methotrexate, in patients with Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL). METHODS: Twenty-four patients (aged 7 days - 22.2 years) with 26 OmR placements were identified for a total of 25,009 OmR days between 1990 and 2019. Methotrexate cerebrospinal fluid (CSF) concentrations (n = 124) were analyzed from 59 courses of OmR therapy in 15 patients. Twenty-one courses involved methotrexate dosing on day 0 only, whereas 38 courses involved booster dosing on days 1, 2, or both. We simulated the time CSF methotrexate concentrations remained > 1 µM for 3 days given various dosing regimens. RESULTS: CSF methotrexate exposure was higher in those who concurrently received systemic methotrexate than via OmR alone (p < 10- 7). Our simulations showed that current intraventricular methotrexate boosting strategy for patients ≥ 3 years of age maintained CSF methotrexate concentrations ≥ 1 µM for 72 h 40% of the time. Alternatively, other boosting strategies were predicted to achieve CSF methotrexate concentrations ≥ 1 µM for 72 h between 46 and 72% of the time. CONCLUSIONS: OmR were able to be safely placed and administer intraventricular methotrexate with and without boost doses in patients from 7 days to 22 years old. Boosting strategies are predicted to increase CSF methotrexate concentrations ≥ 1 µM for 72 h.

Free-Hand Intracerebroventricular Injections in Mice.

The investigation of neuroendocrine systems often requires the delivery of drugs, viruses, or other experimental agents directly into the brains of mice. An intracerebroventricular (ICV) injection allows the widespread delivery of the experimental agent throughout the brain (particularly in the structures near the ventricles). Here, methods for making free-hand ICV injections in adult mice are described. By using visual and tactile landmarks on the heads of mice, injections into the lateral ventricles can be made rapidly and reliably. The injections are made with a glass syringe held in the experimenter's hand and placed at approximate distances from the landmarks. Thus, this technique does not require a stereotaxic frame. Furthermore, this technique requires only brief isoflurane anesthesia, which permits the subsequent assessment of mouse behavior and/or physiology in awake, freely behaving mice. Free-hand ICV injection is a powerful tool for the efficient delivery of experimental agents into the brains of living mice and can be combined with other techniques such as frequent blood sampling, neural circuit manipulation, or in vivo recording to investigate neuroendocrine processes.

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage.

BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

Orexin deficiency modulates the dipsogenic effects of angiotensin II in a sex-dependent manner.

The orexin (hypocretin) neuropeptide system is an important regulator of ingestive behaviors, i.e., it promotes food and water intake. Here, we investigated the role of orexin in drinking induced by the potent dipsogen angiotensin II (ANG II). Specifically, male and female orexin-deficient mice received intracerebroventricular (ICV) injections of ANG II, followed by measuring their water intake within 15 min. We found that lower doses of ANG II (100 ng) significantly stimulated drinking in males but not in females, indicating a general sex-dependent effect that was not affected by orexin deficiency. However, higher doses of ANG II (500 ng) were sufficient to induce drinking in female wild-type mice, while female orexin-deficient mice still did not respond to the dipsogenic properties of ANG II. In conclusion, these results suggest sex-dependent effects in ANG II-induced drinking and further support the sexual dimorphism of orexin system functions.

The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model.

Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus.

Role of central adiponectin and its interactions with NPY and GABAergic systems on food intake in neonatal layer chicken.

BACKGROUND & AIM: Adiponectin is a member of the adipokine family and contributes to regulating energy homeostasis, reproduction, and various biological functions, such as insulin receptor signaling pathway sensitivity, mitochondrial biogenesis, oxidative metabolism, neurogenesis, and suppression of inflammation. This study aimed to investigate the effects of intracerebroventricular (ICV) injection of adiponectin and its interaction with the neuropeptide Y (NPY) and GABAergic systems on central appetite regulation in neonatal layer-type chickens. MATERIALS & METHODS: In this study, 6 experiments were conducted, each of which included 4 experimental groups. In the first experiment, the chickens were injected with saline and adiponectin (20.73, 41.45, and 62.18 nmol). In the second experiment, saline, adiponectin (62.18 nmol), B5063 (NPY1 receptor antagonist, 2.12 nmol), and simultaneous injections of adiponectin and B5063 were performed. Experiments 3 to 6 were done in the same way to experiment 1, but the chickens were injected with SF22 (NPY2 receptor antagonist, 2.66 nmol), SML0891 (NPY5 receptor antagonist, 2.89 nmol), picrotoxin (GABAA receptor antagonist, 0.89 nmol), CGP54626 (GABAB receptor antagonist, 0.047 nmol) instead of B5063. Feed consumption was measured 120 min after the injection. RESULTS: A dose-dependent increase in appetite was observed after the injection of adiponectin (20.73, 41.45, and 62.18 nmol) (P < 0.05). The injection of B5063 + adiponectin attenuated the hyperphagic effect of adiponectin (P < 0.05). In addition, co-injection of picrotoxin and adiponectin significantly decreased adiponectin-induced hyperphagia (P < 0.05). In addition, adiponectin significantly increased the number of steps, jumps, exploratory food, pecks, and standing time, while decreasing sitting time and rest time (P < 0.05). CONCLUSION: These results suggest that the hyperphagic effects of adiponectin are probably mediated through NPY1 and GABAA receptors in neonatal layer-type chickens.

Outcomes of Combined Endoscopic Surgery and Fibrinolytic Treatment Protocol for Intraventricular Hemorrhage: A Randomized Controlled Trial.

BACKGROUND: Intraventricular fibrinolysis (IVF) and endoscopic surgery (ES) are the new promising treatment strategies to enhance the rate of hematoma clearance, which might improve functional outcome. This study investigated and compared the outcomes among these interventions. METHODS: A randomized (1:1) double-blinded trial was carried out between August 2018 and December 2021. The intervention and control groups comprised patients receiving IVF and/or ES and external ventricular drainage (EVD), respectively. All participants had experienced primary or secondary intraventricular hemorrhage (IVH) from spontaneous intracerebral hemorrhage with obstructive hydrocephalus complications. The primary outcome was modified Rankin Scale score 180 days post treatment. Interim assessments were planned for every 50 participants enrolled to ensure safety and efficacy. RESULTS: After enrollment of 110 participants (55 participants in each group), there was a difference in 30-day mortality (2 [3.6%] vs. 13 [32.7%] in the EVD group, P = 0.002), reaching the predetermined boundaries for termination of the trial. We demonstrated a better favorable outcome (modified Rankin Scale score 0-3) at 180 days in the intervention group, compared with the control group (35 [63.6%] vs. 24 [43.6%], P = 0.04). Participants in the intervention group experienced a higher IVH removal rate (91% [9.0] vs. 69.5% [38.0], P < 0.01) and had lower shunt conversion (1 [1.8%] vs. 16 [29.3%], P < 0.01). Treatment complications were comparable between the two groups. CONCLUSIONS: This study demonstrated that combined ES and IVF is safe and effective for the treatment of IVH. In addition, it concluded that aggressive but safe procedures used to remove IVH could improve clinical outcome in patients with IVH.

Clinical Efficacy of Intraventricular rt-PA (Actilyse®) in the Outcome of Patients with Spontaneous Intraventricular Hemorrhage.

AIM: To evaluate the effectiveness of intraventricular injection of rt-PA (Actilyse®) in patients with spontaneous intraventricular hemorrhage (IVH) who had undergone external ventricular drainage (EVD). MATERIAL AND METHODS: This randomized clinical trial recruited 60 patients with spontaneous IVH who had undergone EVD due to the signs of hydrocephalus. The patients were randomly divided into two groups, including a group receiving intraventricular injection of rt-PA and the other normal saline. RESULTS: Both groups receiving rt-PA Actilyse® (n=28) or placebo (n=32) were male by majority (58.33%). We found no difference in the prevalence of meningitis and brain infection (35.7% vs. 37.5%, p=0.665). Changes in hematoma volume at the end of the fourth day compared to the first day after EVD differed significantly between the two groups (p=0.004). The majority (64.29%) showed a decrease in the rt-PA group, but in the placebo group, the majority (53.13%) remained constant. As a result, changes in the rt-PA group were significantly higher than those in the placebo group. Improvements in the level of consciousness (GCS) at the end of the fourth day compared to the first day after EVD implantation was 1.07 units in the Actilyse® group and -1.91 in the placebo group. As shown, the fourth day showed significant differences between the two groups (p < 0.001). Improvements in the Glasgow Coma Scale (GCS) were observed at the end of the period. CONCLUSION: It can be concluded that intraventricular injection of rt-PA (Actilyse®) can effectively reduce the volume of hematoma and improve the level of consciousness (GCS) during treatment. Intraventricular injection of 2-mg rt-PA is safe for patients and does not cause any acute complications such as cerebral hematoma expansion.

Meningitis por Listeria: administración de gentamicina intraventricular y monitorización de concentraciones en líquido cefalorraquídeo / Listeria meningitis: administration of intraventricular gentamicin and monitoring of concentrations in cerebrospinal fluid

La Listeria continúa siendo una posible etiología de meningitis bacteriana en nuestro medio, siendo causa más frecuente en neonatos, ancianos o pacientes inmunodeprimidos. Debido a la gravedad y la mortalidad asociada, resulta de gran interés disponer de nuevas herramientas que permitan un manejo clínico y farmacológico más eficaz.Presentamos un caso de meningitis por Listeria que ingresa en la Unidad de Cuidados Intensivos. Dada la escasa penetración de la gentamicina en el sistema nervioso central y siendo ésta uno de los tratamientos de elección en las guías clínicas de referencia, se decide la administración de gentamicina intraventricular llevando a cabo una monitorización de concentraciones de gentamicina en líquido cefalorraquídeo (LCR).Debido a la alta variabilidad farmacocinética del paciente crítico, la monitorización de concentraciones en LCR de gentamicina tras su administración intraventricular puede resultar de gran utilidad para asegurar el alcance de concentraciones de fármaco que permitan una mayor eficacia del tratamiento. (AU)

Listeria is currently a possible etiology of bacterial meningitis in our society, being one more frequent cause in neonates, elderly or immunosuppressed patients. Due to the severity and mortality associated, it is therefore very useful to have new tools that allow a more effective clinical and pharmacological management.We present a case of Listeria meningitis admitted to the Intensive Care Unit. Given the low penetration of gentamicin into the central nervous system and being one of the treatments of choice in the clinical reference guidelines, the administration of intraventricular gentamicin was decided by monitoring the concentrations of gentamicin in cerebrospinal fluid (CSF).Due to the high pharmacokinetic variability of the critically ill patient, monitoring CSF concentrations of gentamicin after intraventricular administration can be very useful to ensure the achievement of drug concentrations that allow greater treatment efficacy. (AU)