Rotarod Research Articles

Assessment of the effect of solid herbal extract of primula veris l on the physical performance of rats after chronic alcohol intoxication

The aim of this study was to evaluate the effect of solid herbal extract of Primula Veris L. and comparison drugs phenotropil and mildronate on the physical performance of female rats after chronic alcohol intoxication (CAI). CAI was modeled by replacing drinking water for 6 months with a 10 % solution of ethyl alcohol with sucrose (50 g/l). At the age of 16 months, the “Rotarod performance test”, “The horizontal rope walking test” and “Forced swim test with weight load” were performed. After CAI, rats show a deterioration in coordination and motor activity, a decrease in muscle strength and aerobic-anaerobic endurance. Solid herbal extract of Primula Veris L., phenotropil and mildronate contributed to an increase in the physical performance of animals after CAI.

Dysregulated mTOR networks in experimental sporadic Alzheimer's disease.

Beyond the signature amyloid-beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been shown to exhibit dysregulated metabolic signaling through insulin and insulin-like growth factor (IGF) networks that crosstalk with the mechanistic target of rapamycin (mTOR). Its broad impact on brain structure and function suggests that mTOR is likely an important therapeutic target for AD. This study characterizes temporal lobe (TL) mTOR signaling abnormalities in a rat model of sporadic AD neurodegeneration. Long Evans rats were given intracerebroventricular injections of streptozotocin (ic-STZ) or saline (control), and 4 weeks later, they were administered neurobehavioral tests followed by terminal harvesting of the TLs for histopathological study and measurement of AD biomarkers, neuroinflammatory/oxidative stress markers, and total and phosphorylated insulin/IGF-1-Akt-mTOR pathway signaling molecules. Rats treated with ic-STZ exhibited significantly impaired performance on Rotarod (RR) and Morris Water Maze (MWM) tests, brain atrophy, TL and hippocampal neuronal and white matter degeneration, and elevated TL pTau, AβPP, Aβ, AChE, 4-HNE, and GAPDH and reduced ubiquitin, IL-2, IL-6, and IFN-γ immunoreactivities. In addition, ic-STZ reduced TL pY1135/1136-IGF-1R, Akt, PTEN, pS380-PTEN, pS2448-mTOR, p70S6K, pT412-p70S6K, p/T-pT412-p70S6K, p/T-Rictor, and p/T-Raptor. Experimental ic-STZ-induced sporadic AD-type neurodegeneration with neurobehavioral dysfunctions associated with inhibition of mTOR signaling networks linked to energy metabolism, plasticity, and white matter integrity.

Properties of layer V pyramidal neurons in the primary motor cortex that represent acquired motor skills

Layer V neurons in primary motor cortex (M1) are required for motor skill learning. We analyzed training-induced plasticity using a whole-cell slice patch-clamp technique with a rotor rod task, and found that training induces diverse changes in intrinsic properties and synaptic plasticity in M1 layer V neurons. Although the causal relationship between specific cellular changes and motor performance is unclear, by linking individual motor performance to cellular/synaptic functions, we identified several cellular and synaptic parameters that represent acquired motor skills. With respect to cellular properties, motor performance was positively correlated with resting membrane potential and fast afterhyperpolarization, but not with the membrane resistance, capacitance, or threshold. With respect to synaptic function, the performance was positively correlated with AMPA receptor-mediated postsynaptic currents, but not with GABAA receptor-mediated postsynaptic currents. With respect to live imaging analysis in Thy1-YFP mice, we further demonstrated a cross-correlation between motor performance, spine head volume, and self-entropy per spine. In the present study, we identified several changes in M1 layer V pyramidal neurons after motor training that represent acquired motor skills. Furthermore, training increased extracellular acetylcholine levels known to promote synaptic plasticity, which is correlated with individual motor performance. These results suggest that systematic control of specific intracellular parameters and enhancement of synaptic plasticity in M1 layer V neurons may be useful for improving motor skills.

ML218 modulates calcium binding protein, oxidative stress, and inflammation during ischemia-reperfusion brain injury in mice

Cerebral ischemia disrupts calcium homeostasis in the brain causing excitotoxicity, oxidative stress, inflammation, and neuronal cell apoptosis. During ischemic conditions, T-type calcium channel channels contribute to increase in intracellular calcium ions in both neurons and glial cells therefore, the current study hypothesizes the antagonism of these channels using ML218, a novel specific T-Type inhibitor in experimental model of cerebral ischemia-reperfusion (CI/R) brain injury. CI/R injury was induced in Swiss Albino mice by occlusion of common carotid arteries followed by reperfusion. Animals were assessed for learning and memory (MWM), motor coordination (Rota rod), neurological function (neurological deficit score), cerebral infarction, edema, and histopathological alterations. Biochemical assessments were made for calcium binding proteins (Calmodulin- CaM, calcium/calmodulin-dependent protein kinase II-CaMKII, S100B), oxidative stress (4-hydroxy 2-nonenal-4-HNE, glutathione-GSH, inflammation (nuclear factor kappa-light-chain-enhancer of activated B-p65-NF-kB, tumor necrosis factor-TNF-α, interleukin-IL-10) inducible nitric oxide synthase (iNOS) levels, and acetylcholinesterase activity (AChE) in brain supernatants. Furthermore, serum levels of NF-kB, iNOS, and S100B were also assessed. CI/R animals showed impairment in learning, memory, motor coordination, and neurological function along with increase in cerebral infarction, edema, and histopathological alterations. Furthermore, increase in brain calcium binding proteins, oxidative stress, inflammation, and AChE activity along with serum NF-kB, iNOS, and S100B levels were recorded in CI/R animals. Administration of ML218 (5 mg/kg and 10 mg/kg; i.p.) was observed to recuperate CI/R induced impairments in behavioral, biochemical, and histopathological analysis. Hence, it may be concluded that ML218 mediates neuroprotection during CI/R via decreasing brain and serum calcium binding proteins, inflammation, iNOS, and oxidative stress markers.

Preliminary Promising Findings for Manganese Chloride as a Novel Radiation Countermeasure Against Acute Radiation Syndrome.

Military members and first responders may, at moment's notice, be asked to assist in incidents that may result in radiation exposure such as Operation Tomadachi in which the U.S. Navy provided significant relief for the Fukushima Daiichi Nuclear Reactor accident in Japan after an earthquake and tsunami in 2011. We are also currently facing potential threats from nuclear power plants in the Ukraine should a power disruption to a nuclear plant interfere with cooling or other safety measures. Exposure to high doses of radiation results in acute radiation syndrome (ARS) characterized by symptoms arising from hematopoietic, gastrointestinal, and neurovascular injuries. Although there are mitigators FDA approved to treat ARS, there are currently no FDA-approved prophylactic medical interventions to help protect persons who may need to respond to radiation emergencies. There is strong evidence that manganese (Mn) has radiation protective efficacy as a promising prophylactic countermeasure. All animal procedures were approved by the Institutional Animal Care and Use Committee. Male and female B6D2F1J mice, 10 to 11 weeks old, were used for neurotoxicity studies and temporal effects of Mn. Four groups were evaluated: (1) vehicle injection, (2) dose of 4.5 mg/kg for 3 days, (3) dose of 13.5 mg/kg, and (4) sham. Irradiated mice were exposed to 9.5 Gy whole body Co60 γ-radiation. MRI was performed with a high dose of manganese chloride (MnCl2) (150 mg/kg) to assess the distribution of the MnCl2. The mice have promising survival curves (highest survival-13.5 mg/kg dose over 3 days of MnCl2 at 80% [87% female, 73% male] P = 0.0004). The complete blood count (CBC) results demonstrated a typical hematopoietic response in all of the irradiated groups, followed by mildly accelerated recovery by day 28 in the treated groups. No difference between groups was measured by Rota Rod, DigiGait, and Y-maze. Histologic evaluation of the bone marrow sections in the group given 13.5 mg/kg dose over 3 days had the best return to cellularity at 80%. MRI showed a systemic distribution of MnCl2. The preliminary data suggest that a dose of 13.5 mg/kg of MnCl2 given over 3 days prior to exposure of radiation may have a protective benefit while not exhibiting the neurobehavioral problems. A countermeasure that can prophylactically protect emergency personnel entering an area contaminated with high levels of radiation is needed, especially in light that nuclear accidents are a continued global threat. There is a need for a protective agent with easy long-term storage, easy to transport, easy to administer, and low cost. Histologic evaluation supports the promising effect of MnCl2 in protecting tissue, especially the bone marrow using the dose given over 3 days (4.5 mg/kg per day) of MnCl2. Initial experiments show that MnCl2 is a promising safe and effective prophylactic countermeasure against ARS. MRI data support the systemic distribution of MnCl2 which is needed in order to protect multiple tissues in the body. The pathology data in bone marrow and the brain support faster recovery from radiation exposure in the treated animals and decreased organ damage.

Therapeutic Potential of Olfactory Ensheathing Cells and Adipose-Derived Stem Cells in Osteoarthritis: Insights from Preclinical Studies.

Olfactory-ensheathing cells (OECs) are known for their role in neuronal regeneration and potential to promote tissue repair. Adipose-derived stem cells (ADSCs), characterized by mesenchymal stem cell (MSC) traits, display a fibroblast-like morphology and express MSC surface markers, making them suitable for regenerative therapies for osteoarthritis (OA). In this study, OECs and ADSCs were derived from tissues and characterized for their morphology, surface marker expression, and differentiation capabilities. Collagenase-induced OA was created in 10-week-old C57BL/6 mice, followed by intra-articular injections of ADSCs (1 × 105), OECs (1 × 105), or a higher dose of OECs (5 × 105). Therapeutic efficacy was evaluated using rotarod performance tests, MRI, histology, and immunohistochemistry. Both cell types exhibited typical MSC characteristics and successfully differentiated into adipocytes, osteoblasts, and chondrocytes, confirmed by gene expression and staining. Transplantation significantly improved rotarod performance and preserved cartilage integrity, as seen in MRI and histology, with reduced cartilage destruction and increased chondrocytes. Immunohistochemistry showed elevated type II collagen and aggrecan in treated joints, indicating hyaline cartilage formation, and reduced MMP13 and IL-1β expression, suggesting decreased inflammation and catabolic activity. These findings highlight the regenerative potential of OECs and ADSCs in treating OA by preserving cartilage, promoting chondrocyte proliferation, and reducing inflammation. Further research is needed to optimize delivery methods and evaluate long-term clinical outcomes.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1β and PARP1 pathways

BackgroundFibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. MethodsGamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. ResultsN-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1β and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. ConclusionThis study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

Synthesis, In vivo, and In silico Evaluation of New Pyrazoline-Benzothiazole Conjugates as Antiepileptic Agents.

New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. All the synthesized compounds were characterized by thin layer chromatography and spectral analysis. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models, including maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The neurotoxic and antidepression effects of the synthesized compounds were checked by utilizing rotarod apparatus, and motor impairment test (by actophotometer) respectively. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential compared to standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test revealed that the synthesized compounds are also good antidepressants. In-silico studies have been performed for calculation of pharmacophore pattern, prediction of pharmacokinetic properties which determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds and their possible mechanism of antiepileptic action i. e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.

Granulocyte- Macrophage Colony-Stimulating Factor Reverses Immunosuppression Acutely Following a Traumatic Brain Injury and Hemorrhage Polytrauma in a Juvenile Male Rat Model.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

Anti-Parkinson potential of hesperetin nanoparticles: in vivo and in silico investigations

Parkinson’s disease (PD) is characterised by the gradual demise of dopaminergic neurons. In recent years, there has been significant interest in herbal treatments. In this study, hesperetin nanoparticles (HTN) were developed and compared their anti-PD potential with hesperetin (HT) on rotenone induced PD rats. Molecular docking was also performed to evaluate the binding affinity of hesperetin on pathological protein, i.e. D2 dopamine receptors (DR2), using Auto Dock Vina tools. The results showed a higher binding relationship of HTN on dopamine receptors (−7.2 kcal/mol) compared to L-dopa (−6.4 kcal/mol), supporting their potential as drug candidates for PD therapy. HTN was effectively synthesised using the fabrication technique and characterised by zeta potential and SEM analysis. HTN had favourable characteristics, including a size of 249.8 ± 14.9 nm and a Z-potential of −32.9 mV. After being administered orally, HTN demonstrated a notable anti-Parkinsonian effects, indicated by the significant improvement in motor function as assessed by the rota rod test (p < .001***), pole test (p < .001***), stair test (p < .01**), wood walk test (p < .01**) and an increase in substantia nigra (SN) antioxidant levels, CAT (p < .001***), SOD (p < .001***), GSH (p < .01**). Additionally, HTN led to increased dopamine levels (p < .01**) and a decrease in the oxidant system, MDA levels (p < .01**). Furthermore, histopathological examination revealed decreased SN neuronal necrosis in diseased animals treated with HTN compared to those treated with HT in a rat model of Parkinson’s disease. Therefore, HTN can be regarded as a viable platform for efficient therapy of PD.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.

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. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice

BackgroundAlzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes.ResultsThe current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P < 0.0001).ConclusionsThe observed memory ameliorating effect of novel N-benzyl pyridine-2-one makes them as a a good choice for treatment of individuals with cognitive impairment.Graphical abstract

ALKBH8 contributes to neurological function through oxidative stress regulation.

Transfer RNA (tRNA) modification is essential for proper protein translation, as these modifications play important roles in several biological functions and disease pathophysiologies. AlkB homolog 8 (ALKBH8) is one of the nine mammalian ALKBH family molecules known to regulate selenoprotein translation through the modification of the wobble uridine (U34) in tRNA; however, its specific biological roles remain unclear. In this study, we investigated the role of ALKBH8 using Alkbh8-knockout (Albkh8-/-) mice, which were observed to have reduced 5-methoxycarbonylmethyluridine (mcm5U) and (S)-5-methoxycarbonylhydroxymethyluridine levels; notably, the mcm5U level was partially compensated only in the brain. The results of the novel object recognition test showed reduction in time to explore a novel object in Albkh8-/- mice; increased latency to fall in the rotarod performance test and latency to the immobility period in the forced swim test were also observed. These abnormal behaviors indicate dysfunction of the central nervous system. Furthermore, we observed reduced brain weight and ischemic pathological changes in the cerebral cortex and hippocampus in the form of weak eosin staining in the fiber tracts adjacent to the hippocampal cornu ammonis 1 region and an increase in pyramidal cells in the temporal lobe. Concordantly, we identified the differential expression of oxidative stress-related proteins and metabolites in the cerebral cortex and hippocampus using omics analyses. Finally, neurons and glial cells derived from Albkh8-/- mice show reduced mitochondrial membrane potential. Collectively, these findings indicate that ALKBH8 maintains neural function through an oxidative stress-regulatory mechanism.

Effects of Cholinergic Receptor Activation and Magnetic Fields on Motor Behavior in Ischemic Gerbils

Introduction: Ischemic stroke stands as a leading global cause of death and disability, prompting the need for animal model experiments in stroke research and the protection of motor function. Recently, magnetic fields have gained significant interest in various biological contexts, showing promise in preserving neurons and reversing behavioral and morphological changes in stroke models. This study explores the potential synergy between static magnetic field and nAChR agonist administration in safeguarding motor behavior in ischemic gerbils. Objective: To determine whether the combined use of a static magnetic field and an agonist for nicotinic acetylcholine receptors (nAChR) can preserve motor behavior in ischemic gerbils.Methods: In this experimental study, 72 Mongolian gerbils were randomly allocated into nine groups (n=8): S, SISM, SINSM, ISM, INP, ISP, INSM, INNP, INSP, distributed according to surgical procedure and treatment. The animals were trained and evaluated on the Rotarod (RR) to assess motor performance.Results: The main finding was the preservation of motor behavior in the Sham Ischemia and Nicotine and Sham Magnetic Stimulation (SINSM) and Ischemia and Nicotine and South Pole Magnetic Field (INSP) groups, as evidenced by the results of the RR test.Conclusions: The findings are consistent with previous literature and provide insight into the mechanism of potentiation, as results showed that adding a nAChR agonist to the magnetic field preserved motor performance in the RR test of ischemic animals.

Effect of pretreatment with Devil's Claw on locomotor activity, infarct volume, and neuronal density in focal cerebral ischemia in rats.

Stroke is a highly prevalent and devastating condition affecting millions worldwide. The Devil's Claw (DCW) plant is a native African plant whose anti-inflammatory, antioxidant, and neuroprotective properties have been investigated. We postulated that DCW could protect the brain injury caused by cerebral ischemia. The rats were randomly divided into four groups. The sham and control (Ctrl) groups received pretreatment with a distilled water vehicle. Doses of 200 and 400 mg/kg were selected for pretreatment with DCW. The filament or intravascular occlusion method was used for middle cerebral artery occlusion (MCAO). The Triphenyl tetrazolium chloride (TTC) staining method was used to investigate the infarct zone and penumbra volume. The neuroprotective effect of DCW was measured by hematoxylin staining. Movement performance was evaluated from neurological deficit score, rotarod performance, and open field tests. TTC staining showed that the DCW/400 group could maintain the penumbra's structure and reduce the infarct volume compared to the Ctrl group (p<0.001). Histological studies confirmed the neuroprotective properties of DCW at doses of 200 and 400 mg/kg compared to the Ctrl group (p<0.01 and p<0.0001, respectively). The results of behavioral tests showed an improvement in behavioral performance in pretreatment 400 mg/kg doses compare to Ctrl group (p<0.0001). The study showed that pretreatment with DCW with its neuron protection potential reduces the infarct area and restores motor function after MCAO.

The Absence of Gastrointestinal Redox Dyshomeostasis in the Brain-First Rat Model of Parkinson’s Disease Induced by Bilateral Intrastriatal 6-Hydroxydopamine

The gut-brain axis plays an important role in Parkinson’s disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test, and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular-weight thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Both univariate and multivariate models analyzing redox biomarkers indicate that significant disturbances in gastrointestinal redox balance are not present. The findings demonstrate that motor impairment observed in the brain-first 6-OHDA model of PD can occur without concurrent redox imbalances in the gastrointestinal system.

The interaction of Suk-Saiyasna remedy with GABAA and CB1 receptor-targeting drugs: Enhancing hypnotic and sedative effects in in vivo models.

The Suk-Saiyasna remedy, an herbal treatment, was historically used but ceased due to its cannabis content. After a relaxation of drug control laws in Thailand, its use re-emerged. This study examines the Suk-Saiyasna remedy's impact on rodent behavior and its receptor effects. This study was conducted to assess the sedative-like effects of the remedy on mice. The mice were divided into groups receiving 0.6, 3, 30, and 60 mg/kg extracts, with negative controls for comparison. We also investigated the impact on receptors, utilizing negative controls and pretreatment with receptor blockers, followed by either a negative control or a 60 mg/kg extract. Furthermore, this study investigated the behavioral aspects of mice, including anxiolytic effects, antidepressant-like effects, and motor coordination, utilizing the elevated plus-maze, open-field, and rotarod performance tests. The Suk-Saiyasna remedy (P < 0.05) decreased significantly in the latent period and increased sleeping time in the treated groups. Moreover, the Suk-Saiyasna remedy also showed efficacy in reaction to GABAA receptors and cannabinoid CB1 receptors (P < 0.05). In addition, positive effects were observed regarding the animal behavior in the arena, as the animal activity, behavior, and muscle coordination were reduced (P < 0.05). The Suk-Saiyasna remedy may be involved in a sedative-hypnotic-like effect in rodents under normal conditions through the modulation of GABAergic neurons and induction of the cannabinoid CB1 receptor mechanism.

Evaluating Motor Dysfunction and Oxidative Stress Induced by Trichloroethylene in Wistar Rats.

Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene (TCE) contributes to the development of Parkinson's disease (PD). TCE induced LRRK2 kinase activity in the rat brain and produced a significant dopaminergic lesion in the nigrostriatal tract with elevated oxidative stress. Here we have utilized TCE-induced PD model for the assessment of test drug. Oral gavage administration of TCE at a dose of 1000mg/kg/day for 6weeks was utilized to induced PD. Muscle grip strength was estimated by rotarod and grid performance test. Motor activity by actophotometer and locomotor stability were assessed by forelimb locomotor scale (FLS) and forelimb step alternation test (FSAT). However, the postural stability was assessed by postural stability test (PST). Biochemical estimation consists of determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), GSH level (reduced glutathione), and nitrite concentration.

Alcohol induced behavioral and immune perturbations are attenuated by activation of CB2 cannabinoid receptors.

The endocannabinoidome (eCBome) is the expanded endocannabinoid system (ECS) and studies show that there is a link between this system and how it modulates alcohol induced neuroinflammation. Using conditional knockout (cKO) mice with selective deletion of cannabinoid type 2 receptors (CB2Rs) in dopamine neurons (DAT-Cnr2) and in microglia (Cx3Cr1-Cnr2), we investigated how CB2Rs modulate behavioral and neuroinflammation induced by alcohol. Behavioral tests including locomotor and wheel running activity, rotarod performance test, and alcohol preference tests were used to evaluate behavioral changes induced by alcohol. Using ELISA assay, we investigated the level of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1α (IL-1α), and interleukin-1β (IL-1β) in the hippocampus of mice. The findings demonstrated that locomotor activity, wheel running, and rotarod performance activities were significantly affected by cell-type specific deletion of CB2Rs in dopamine neurons and microglia. The non-selective CB2R agonist, WIN 55,212-2, reduced alcohol preference in the wild type and cell-type specific CB2R cKO mice. In addition, the result showed that cell-type specific deletion of CB2Rs per se and administration of alcohol to CB2R cKO mice increased the expression of proinflammatory cytokines in the hippocampus. These findings suggest the involvement of CB2Rs in modulating behavioral and immune alterations induced by alcohol.