جستجوی مقالات مرتبط با کلیدواژه « Neuroprotection » در نشریات گروه « پزشکی »

Neurodegenerative diseases and brain tumors are significant medical ailments that impact the brain. Administering therapeutic drugs to the brain is more challenging compared to other organs or systems. The existence of the blood-brain barrier (BBB) poses significant complexities and challenges in delivering drugs to the brain. This study explores the potential of Fullerene nanoparticles as a novel therapeutic agent for delivering drugs to the brain and their neuroprotective roles within the central nervous system. Novel drug delivery methods have been devised to surmount obstacles posed by BBB and accomplish targeted drug delivery to the brain. Carbon nanostructures are an excellent option for delivering drugs into the brain because they have favorable biocompatibility and can easily penetrate BBB. Furthermore, these nanocarriers has the potential to serve as a therapeutic agent inside the central nervous system, exhibiting neurogenerative properties in some cases. Additionally, their impact on the proliferation of neurons and their ability to counteract the formation of amyloid plaques is particularly remarkable. Carbon-based nanomaterials, including zero-dimensional fullerene (C60), one-dimensional carbon nanotubes (CNTs), and two-dimensional graphene, have shown significant potential in the area of nanomedicine. This is attributed to their unique blend of chemical and physical characteristics, as well as their hydrophobic surfaces. Fullerene nanoparticles have the potential to greatly improve the treatment of brain illnesses by serving as both carriers and therapeutic agents.

 Alterations of antioxidant defense, neuroinflammation, and neurodegeneration are common pathological occurrences associated with neurodegenerative diseases. This study evaluated the neuroprotective effect of Launaea taraxacifolia (LT), popularly known as African Wild lettuce, against neuroinflammation, memory loss, and neurobehavioral deficit.

 Adult Wistar rats were used following random assignment into groups 1 to 5. Group one was the normal control. Groups four to five received 40 mg/kg Nω-nitro-l-arginine methyl ester (L-NAME). In addition to L-NAME exposure, groups three and four received 100 and 200 mg/kg LT, whereas group five received 10 mg/kg lisinopril. The experiment lasted for five weeks. Markers of oxidative stress, neurobehavioural studies, histology, and immunohistochemistry of glial fibrillary acidic protein (GFAP), ionised calcium-binding adaptor molecule 1 (Iba-1), as well as anti-calbindin for staining astrocytes, microglia, and Purkinje cells were determined.

 Malondialdehyde (MDA) and protein carbonyl in the L-NAME alone group were heightened compared to those treated with LT. However, treatment with LT significantly reduced neuronal oxidative stress, neuroinflammation, and neurobehavioural changes. Quantitative analysis of immunohistochemical staining revealed heightened glial fibrillary acidic protein (GFAP), ionised calcium-binding adaptor molecule 1 (Iba-1), as well as anti-calbindin as indicated by astrogliosis, microgliosis, and Purkinje cell degeneration in untreated rats. Moreover, the observed ultrastructural anarchy induced by L-NAME was restored in rats treated with LT (P<0.05).

 Together, the leaf extract of LT can be effective as a neuroprotective drug candidate.

Intraoperative neurophysiological monitoring (IONM) is a valuable technique used during brain tumor resections to assess and preserve neurological function. This case report investigates the impact of intraoperative magnesium sulfate infusion on neuroprotection and muscle relaxation in the context of IONM during brain tumor resection.A 48-year-old male with altered awareness and occasional convulsive movements involving his right upper and lower limbs accompanied by progressive right-sided weakness and occasional sensory disturbances was diagnosed with a left temporal lobe tumor. He underwent craniotomy for tumor resection, with concurrent IONM and an intraoperativemagnesium sulfate infusion. The patient’s neurophysiological parameters, surgical outcomes, and postoperative recovery were analyzed, suggesting a potential synergistic effect between magnesium sulfate and IONM in optimizing patient outcomes.

RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model.

We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model.

The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ- carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK–NTRK2 complex showed more stable and stronger interactions as compared to the RNYK–NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SHSY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318.

The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage and mutation is widely accepted as one of the pathological processes of neurodegenerative diseases. As an mtDNA binding protein, mitochondrial transcription factor A (TFAM) maintains the integrity of mtDNA through transcription, replication, nucleoid formation, damage perception, and DNA repair. In recent works, the overexpression of TFAM increased the mtDNA copy count, promoted mitochondrial function, and improved the neurological dysfunction of neurodegenerative diseases. The role of TFAM in neurodegenerative diseases has been well explained. However, the role of TFAM after surgical brain injury (SBI) has not been studied. In this work, we aimed to study the role of TFAM in the brain after SBI and its mechanism of action. One hour after the occurrence of SBI, tetramethylpyrazine (TMP) was injected into the abdominal cavity of rats, and the brain was collected 48 hr later for testing. The evaluation included neurobehavioral function test, brain water content measurement, immunofluorescence, western blot, TUNEL staining, FJC staining, ROS test, and ATP test.  After SBI, the content of TFAM on the ipsilateral side increased and reached a peak at about 48 hr. After intraperitoneal injection of TMP in rats, 48 hr after SBI, the concentration of TFAM, Bcl-2, and adenosine triphosphate (ATP) increased; the content of caspase-3, reactive oxygen species (ROS), and cerebral edema decreased; and the nerve function significantly improved.  TMP inhibited cell apoptosis after SBI in rats by up-regulating TFAM and protecting brain tissues.

Neurological disorders are the world’s most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice. Forty-two mice were randomly distributed into 7 groups each having 6 animals. Group I; received saline. Group II; received isoproterenol (ISO) 15 mg/kg/day, s.c. for 20 days. Group III, IV; received 50 and 100 mg/kg/day/oral of D-Pinitol, respectively along with ISO for 20 days. Group V; received D-Pinitol 100 mg/kg/day/oral for 20 days. Group VI; received propranolol 20 mg/kg/day/oral and ISO for 20 days. Group VII; received propranolol 20 mg/kg/day/oral for 20 days. On the 21st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses. Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation  (NF-kB, TNF-α, IL-6, and IL-10), and decrease in AchE and BDNF. Co-administration of D-Pinitol (100 mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test. Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.

Acorus calamus Linn. from the Acoraceae family exhibits several benefits in neurological disorders but has not been studied for chronic constriction injury (CCI) of median nerve induced neuropathic pain. Damage to median nerve leads to work-related musculoskeletal disorders (WMSDs). this study aimed to assess the effects of the ethanolic root extract of Acorus calamus (EAC) on CCI-induced neuropathic pain and WMSDs in rats.

Animals were randomly divided into 7 groups of 8 animals each. Group 1. Normal control, 2. Sham control, 3. CCI, 4. CCI+ vehicle (CMC), 5. CCI+gabapentin (50 mg/kg), 6. CCI+EAC (20 mg/kg), 7. CCI+EAC (40 mg/kg). On day 0, rats were subjected to the surgical procedure of exposure and ligation of the median nerve-produced CCI at the forearm level. Pain-sensitive tests (i.e., hot plate test, Randall Selitto test), and functional analysis (i.e., walking track) were performed. Total protein, lipid peroxidation, and histopathological changes were also estimated.

CCI significantly increased thermal and mechanical hyperalgesia, raised median functional index (walking track analysis), and induced biochemical and histological disruptions. Oral administration of EAC (40 mg/kg) and gabapentin (50 mg/kg) notably lowered CCI-induced nociceptive pain threshold, improved median nerve functional index, and mitigated tissue histological alterations.

EAC has been found to decrease CCI-induced neuropathic pain of the median nerve. Its mechanisms likely involve neuroprotective, antioxidant, and anti-inflammatory properties.

Hepatic encephalopathy induces cognitive disturbances. Patients show neuroinflammation due to accumulation of toxic substances. Frankincense has neuroprotective and anti-inflammatory properties. Accordingly, we intended to evaluate the impact of frankincense on memory performance, inflammation, and the amount of hippocampal neurons in bile duct-ligated rats.

The bile duct was ligated in three groups of adult male Wistar rats (BDL groups). In two of these groups, frankincense was administered (100 or 200 mg/kg; by gavage) starting from one week before surgery to 28 days after surgery. The third BDL group received saline. In the sham group, the bile duct was not ligated and the animals received saline. Twenty-eight days after surgery, spatial memory was evaluated by the Morris water maze test. Five rats from each group were sacrificed to measure the expression of the hippocampal tumor necrosis factor-alpha (TNF-α). Three rats from each group were perfused to determine the amount of hippocampal neurons. 

Bile duct ligation impaired memory acquisition, while frankincense amended it. Bile duct ligation significantly increased the expression of TNF-α. Frankincense reduced TNF-α in BDL rats, significantly. The number of neurons in the hippocampal CA1 and CA3 areas was significantly lower in the BDL group and in the group that received frankincense (100 mg/kg) equated to the sham group. Frankincense (200 mg/kg) augmented the amount of neurons in the CA1 area, slightly and in the CA3 area, significantly. 

The results indicate the anti-inflammatory and neuroprotective effects of frankincense in bile duct ligation-induced hepatic encephalopathy.

 Neuroinflammation and oxidative stress are critical factors involved in the pathogenesis of Parkinson's disease (PD), the second most common progressive neurodegenerative disease. Additionally, lipid peroxidation end products contribute to inflammatory responses by activating pro-inflammatory genes. Lipid peroxidation occurs as a result of either the overproduction of intracellular reactive oxygen species (ROS) or the reaction of cyclooxygenases (COXs).

 In this study, we examined the role of 1,5-diaryl pyrrole derivatives against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in a cellular model of PD.

 PC12 cells were pre-treated with compounds 2-(4-chlorophenyl)-5-methyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrole (A), 2-(4-chlorophenyl)-1-(4-methoxyphenyl)-5-methyl-1H-pyrrole (B), and 1-(2-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-1H-pyrrole (C), respectively, 24 h before exposure to 6-OHDA. We conducted various assays, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), ROS, and lipid peroxidation assays, Hoechst staining, Annexin V/PI, Western blotting analysis, and prostaglandin E2 (PGE2) determination, to assess the neuroprotective effects of pyrrole derivatives on 6-OHDA-induced neurotoxicity.

 Our results demonstrated that apoptosis induction was inhibited by controlling the lipid peroxidation process in the in vitro model following treatment with compounds A, B, and, somehow, C. Furthermore, compounds A and C likely act by suppressing the COX-2/PGE2 pathway, a mechanism not attributed to compound B.

 These findings suggest that the novel synthetic pyrrolic derivatives may be considered promising neuroprotective agents that could potentially prevent the progression of PD.

Olive leaf extract (OLE) has robust anti-oxidant and anti-inflammatory properties. A toxic dose of colchicine (COL) injected into the hippocampus disrupts the microtubules’ neuronal structure causing it to be unstable and depolymerized. The objective of the current study was to evaluate the protective effects of OLE treatment on the CA1 hippocampal pyramidal cells of rats that are injected with intracranial COL.

Eighteen rats were divided into control, COL-injected, and OLE-treated-colchicine-injected (COL+OLE) groups (n = 6). A vehicle solution was injected into the hippocampi of the control rats, whereas 15 μg/5 μL of COL was injected into the hippocampi of COL and COL+OLE groups. Forced oral treatment with 100 mg/kg OLE was commenced a week later and continued for 15 days. Short-term memory (STM) test using the Morris water maze (MWM) was performed followed by the retention probe memory test. Hippocampal samples from animals of all groups were collected for histopathological examination and qualitative assessment of the viable pyramidal cells at the CA1 hippocampal region.

The control and COL+OLE groups demonstrated significantly better performance (P < 0.05) in the STM test and its subsequent retention probe memory test as compared to the COL group. The morphology of the pyramidal cells of the COL+OLE treated rats was preserved, showing less distortion than the COL group.

OLE treatment led to a considerable preservation in the STM function of rats challenged with intrahippocampal COL injection. This memory improvement of the OLE might be attributed to its promising neuroprotective potential on hippocampal pyramidal cells.

Parkinson’s disease (PD) is a neurodegenerative disorder, basically manifested by motor symptoms. However, there are other associated non-motor features in PD, including depression, anxiety, and cognitive impairments that significantly affect the quality of life. Scientific reports have shown that Sargassum wightii, a brown seaweed, protects against rotenone-induced motor deficits, mitochondrial dysfunction, and oxidative stress in rats. We therefore, undertook this study to evaluate its efficacy in alleviating rotenone-induced non-motor symptoms such as anxiety-like behavior and cognitive deficits in rats.

Rotenone at a dose of 10 mg/kg was given orally for 28 days to induce PD model in male rats. The vehicle and the test drug were given orally daily, 1 hour prior to the rotenone administration. The protective effect of S. wightii (methanol extract at 400 mg/kg dosage) was assessed through an array of tests: Elevated plus maze test, Morris water maze test, and novel object recognition test. On the 28th day, the rats were sacrificed, and hippocampal neurobiochemical analyses were performed using high-performance liquid chromatography (HPLC).

Co-administration of S. wightii reversed the rotenone-induced anxiety-like behavior and cognitive deficits to a significant extent (P < 0.001). It also restored the hippocampal neurotransmitters (5-hydroxytryptamine, dopamine, and 5-hydroxy indole acetic acid) significantly (P < 0.001).

Sargassum wightii provides neuroprotective effects and reduces the non-motor symptoms of PD. Therefore, it might be a novel insight into PD therapy.

 One of the common diseases in different societies is Parkinson's disease (PD), for which no suitable treatment has been found yet. Curcumin a natural compound has shown neuroprotective properties in many studies. Therefore, in this research, the administration of this compound to female mice was studied.

Induction of PD in mice was done by administering 2 mg rotenone, and then a Rotarod test was performed on female mice. Also, 50 mg/kg of curcumin was administered every day for 21 days and its effects were evaluated in PD mice. Finally, the expression levels of bax and bcl-2 were measured in the brain of female mice by RT-PCR technique. GraphPad Prism V.8 software was used for data analysis.

Induction of PD led to a decrease in the performance of mice in the Rotarod test. However, the administration of curcumin to these mice improved their performance. Also, overexpression of bax and downregulation of bcl-2 genes were observed in the brains of PD mice, to whom the administration of curcumin downregulated bax gene and overexpressed bcl-2 gene.

Curcumin has neuroprotective effects in PD conditions, which can be attributed to the change in expressions of the bcl-2 family gene. More studies are needed in this field.

Inflammation plays a major part in brain ischemia. Propolis is a polyphenol-rich hive product with a set of pharmaceutical properties.

This research aims to investigate the impact of water extracts of brown propolis (WEPs) on stroke outcomes and inflammatory responses in a rat model of permanent middle cerebral artery occlusion (MCAO).

This experimental study was conducted in Rafsanjan, Iran, in 2017. WEPs were experimentally prepared from two regions in Iran. Gas chromatography–mass spectrometry and Folin–Ciocalteu assays were used to determine chemical portrayal and the total polyphenol content, respectively. A total of 66 male adult mice were divided randomly into the surgical sham, control (vehicle-treated), and four WEPs-treated animal groups. WEPs-treated groups received doses of 100 and 200 (mg/kg, IP) four times, and their behavioral tests, brain edema, infarct volume, and tumor necrosis factor-alpha (TNF-α) level were evaluated.

The samples were not significantly different in terms of the concentration of the total polyphenol content. Compared to the control, WEPs led to a substantial decrease in the TNF-α level (P<0.05) as well as a subsequent reduction in the brain edema and infarct volume (P<0.001) in all treatment groups. Furthermore, there was a significant improvement in neurological deficits and sensory-motor impairments level (P<0.05).

According to the study findings, WEPs reduce brain ischemia damage, perhaps by exerting a neuroprotective effect on stroke-induced neuroinflammatory responses

The effects of Pb-induced neurotoxicity have been largely established; however, the need for proper neuroprotective agents to mitigate the effects of Pb-induced neurotoxicity remains vague.

This study aimed at investigating the neuroprotective effects of pre-treatment with vitexin and C. cajan extract against Pb-induced neurotoxicity in Wistar rats.

Twenty-four male Wistar rats were randomly assigned into four groups (n=6). The control group was administered 0.5 mL of distilled water, Pb group received Pb acetate (200 mg/kg), vitexin+Pb group received Vitexin (50 mg/kg) an hour before Pb acetate (200 mg/kg), and C. cajan+Pb group received C. cajan (50 mg/kg) an hour before Pb acetate (200 mg/kg). All treatments were done within 28 days. Barnes maze test and novel object recognition (NOR) test were done to ascertain working memory, while the levels of oxidative stress markers (MDA, SOD, and GPx) were also tested. In addition, prefrontal cortical sections were stained with H&E stain, and the immunoreactivity of Iba1 and Nrf2 was examined.

There was a significant decline in working memory in the Pb group, but good working memory was maintained in vitexin and C. cajan pretreated groups. In vitexin and C. cajan pretreated groups, oxidative stress, neuronal damage, and expression of Iba1 were significantly low compared to the Pb group. Also, Nrf2 expression in the Pb group was significantly low compared to other groups.

Pretreatment with vitexin and C. cajan offers neuroprotection against Pb toxicity via antioxidant and anti-inflammation actions. Although both vitexin and C. cajan extract showed neuroprotective abilities, vitexin exhibited better results.

The study aims to estimate the neuroprotective effect of chromone derivatives in the sporadic form of Alzheimer’s disease in the context of the relationship between changes in mitochondrial function and neuroinflammation. Alzheimer’s disease was modeled by injecting Aβ 1-42 fragments into the CA1 part of the hippocampus of animals. The test compounds and memantine were administered orally for 60 days from the moment the pathology was reproduced. The change in cognitive deficit in rats was assessed in the Y-maze test. In the hippocampus of rats, intensity of cellular respiration, activity of mitochondrial enzymes (citrate synthase, aconitase, cytochrome-c-oxidase, and succinate dehydrogenase), concentrations of IL - 6; IL -1β; TNF -α; IL – 10, and cardiolipin were determined. Of the 18 substances, only C3AACP6 and C3AACP7 compounds contributed to the recovery of aerobic metabolism, increased activity of mitochondrial enzymes, and reduced neuroinflammation in the hippocampus of rats. Furthermore, administration of these substances reduced the manifestation of cognitive deficit in animals with Alzheimer’s disease to a degree comparable with memantine. Moreover, in terms of the effect on changes in the activity of mitochondrial enzymes and aerobic metabolism, these substances significantly exceeded memantine. The study showed that from the analyzed chromone derivatives, two compounds C3AACP6 and C3AACP7 could have a neuroprotective effect in Alzheimer’s disease, which is realized through the axis: recovery of mitochondrial function, decrease extramitochondrial cardiolipin, decrease neuroinflammation, neuroprotection.

Morin hydrate (MH) is a bioflavonoid component of many fruits and vegetables. Our previous research demonstrated that MH provides neuroprotection in mouse models of acute restraint stress and sleep deprivation by attenuating hippocampal neuronal damage and enhancing memory. Based on these findings, our study investigated the role of MH in chronic stress-induced neuronal and biochemical perturbations in BALB/c mice.

Male BALB/c mice were divided into 6 groups (n=6). Groups 1 and 2 received vehicle (10 mL/kg normal saline), groups 3-5 received MH (5, 10, 20 mg/kg IP), while group 6 received ginseng (25 mg/kg) daily and 30 minutes afterward were restrained in a plastic cylindrical restrainer for 14 days. 

Immobility time in the forced swim test increased in the MH-treated group, indicating an antidepressant-like effect. Also, a reduction in frequency and duration of open arms exploration was observed in the elevated plus-maze (EPM) test in stressed mice, and administration of MH (5, 10, 20 mg/kg, IP) reversed these effects. An increase in blood levels of glucose, triglycerides, total cholesterol, and brain malondialdehyde and nitrite levels was observed in the stressed groups, which was reversed by MH. Furthermore, MH reversed the stress-induced reduction in HDL cholesterol and glutathione (GSH) levels and attenuated stress-induced alterations in the prefrontal cortex and hippocampus. 

Our findings suggest that MH attenuated chronic restraint stress-behavioral and biochemical perturbations, probably due to its capability to decrease oxidative stress and brain neuronal damage