intracerebroventricular

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota...

Epidemiological studies report an elevated risk of Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed dipeptidyl peptidase 4 (DPP-4) inhibitors. With an objective to characterize clinically translatable doses of DPP-4 inhibitors (gliptins) in a well-characterized PD rodent model, sitagliptin, PF-00734,200 or vehicle were orally administered to rats initiated either 7-days before or 7-days after unilateral medial forebrain bundle 6-hydroxydopamine (6-OHDA) lesioning...

BACKGROUND: Spinal Muscular Atrophy (SMA) is an autosomal-recessive neuromuscular disease affecting children. It is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene resulting in lower motor neuron (MN) degeneration followed by motor impairment, progressive skeletal muscle paralysis and respiratory failure. In addition to the already existing therapies, a possible combinatorial strategy could be represented by the use of adipose-derived mesenchymal stem cells (ASCs) that can be obtained easily and in large amounts from adipose tissue...

Mellpaladines A-C ( 1-3 ) and dopargimine ( 4 ) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine ( 5 ), three additional mellpaladines D-F ( 6-8 ), and serotodopalgimine ( 9 ), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine ( 10 ). The structures of these compounds were determined based on spectrometric and spectroscopic analyses...

BACKGROUND: Apelin has been extensively studied, and emerging experimental evidence suggests that Apelin may have effects on stroke by reducing infarct volume and neurological deficits, inhibiting the apoptosis process and reducing brain water content. However, the credibility of the evidence is uncertain. Thus, we aimed to perform a systematic review and meta-analysis to evaluate preclinical studies that used Apelin for the treatment of transient focal cerebral ischemia. METHODS: Electronic bibliographic databases including PubMed, EMBASE, Scopus, and Google Scholar were searched for finding relevant studies from January 2000 to July 2023...

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 μg/day), DAG (0.2, 1.0, and 5.0 μg/day), or saline (14 μL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg)...

BACKGROUND: Glucuronidation is an essential metabolic pathway for a variety of drugs. IMM-H004 is a novel neuroprotective agent against ischemic stroke, and its glucuronide metabolite IMM-H004G exhibits similar pharmacological activity. Despite possessing a higher molecular weight and polarity, brain exposure of IMM-H004G is much higher than that of IMM-H004. This study aimed to investigate the brain metabolism and transport mechanisms of IMM-H004 and IMM-H004G. METHODS: First, the possibility of IMM-H004 glucuronidation in the brain was evaluated in several human brain cell lines and rat homogenate...

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule...

AIMS: Neuronal cell death is a primary factor that determines the outcome after traumatic brain injury (TBI). We previously revealed the importance of receptor for activated C kinase (RACK1), a multifunctional scaffold protein, in maintaining neuronal survival after TBI, but the specific mechanism remains unclear. The aim of this study was to explore the mechanism underlying RACK1-mediated neuroprotection in TBI. METHODS: TBI model was established using controlled cortical impact injury in Sprague-Dawley rats...

BACKGROUND: Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined. OBJECTIVE: This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO)...

Dopamine (DA) D 2 -like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D 2 -like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D 2 -like receptors including D 2 (D2R) and D 3 (D3R) receptors remain poorly understood. To address this, we developed new pharmacological tools, D 2 -like receptor agonists with diminished and delayed blood-brain barrier capability, to selectively manipulate D2R/D3R signaling in the periphery...

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump...

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile...

Calcitonin gene-related peptide (CGRP) is a neuropeptide that causes anxiety behavior; however, the underlying mechanisms remain unclear. We found that CGRP modulates anxiety behavior by epigenetically regulating the HP1γ-KLF-11-MAOB pathway and depleting dopamine in the dorsal hippocampus. Intracerebroventricular administration of CGRP (0.5 nmol) elicited anxiety-like behaviors in open field, hole-board, and plus-maze tests. Additionally, we observed an increase in monoamine oxidase B (MAOB) levels and a concurrent decrease in dopamine levels in the dorsal hippocampus of mice following CGRP administration...

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures...

Recent evidence suggests that the gut plays a vital role in the development and progression of Alzheimer's disease (AD) by triggering systemic inflammation and oxidative stress. The well-established rat model of AD, induced by intracerebroventricular administration of streptozotocin (STZ-icv), provides valuable insights into the GI implications of neurodegeneration. Notably, this model leads to pathophysiological changes in the gut, including redox dyshomeostasis, resulting from central neuropathology. Our study aimed to investigate the mechanisms underlying gut redox dyshomeostasis and assess the effects of D-galactose, which is known to benefit gut redox homeostasis and alleviate cognitive deficits in this model...

INTRODUCTION: Metabolic dysfunctions are critical in the pathology of Alzheimer's disease. Impaired zinc homeostasis, in particular, is a significant issue in this disease that has yet to be explained. Gene expression of ZIP14 in brain tissue has been previously reported. But to date, only one study has reported reduced ZIP14 levels in aged brain tissue. We investigated how dietary zinc deprivation and supplementation impact ZIP14 levels in the cerebral cortex in rats with sporadic Alzheimer's disease (sAH) produced by intracerebroventricular streptozotocin (icv-STZ)...

Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Cav 1.2 and Cav 1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission...

Salidroside, a principal bioactive component of Rhodiola crenulata, is neuroprotective across a wide time window in stroke models. We investigated whether salidroside induced neurogenesis after cerebral ischemia and aimed to identify its primary molecular targets. Rats, subjected to transient 2 h of middle cerebral artery occlusion (MCAO), received intraperitoneal vehicle or salidroside ± intracerebroventricular HSC70 inhibitor VER155008 or TrkB inhibitor ANA-12 for up to 7 days. MRI, behavioural tests, immunofluorescent staining and western blotting measured effects of salidroside...

BACKGROUND: G protein-coupled receptor 40 (GPR40) is a potential drug target for Alzheimer's disease (AD), and its agonist GW9508 ameliorates cognitive impairment by intravenous administration. OBJECTIVES: The present study was conducted to investigate the efficacy of GW9508 administered peripherally on cognitive dysfunction in streptozotocin (STZ)-induced AD mice. METHODS: Seventy male ICR mice were randomly divided into seven groups: vehicle sham group, model, Donepezil, GW9508-L, GW9508-M, GW9508-H, and GW1100 + GW9508-H groups, and administered either vehicle (artificial cerebrospinal fluid [aCSF]) or STZ (3 mg/kg in the vehicle) once a day (9:00 a...