Corrigendum: Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse.

[This corrects the article DOI: 10.3389/fphar.2018.00757.].

Effects of ELF-PEMF exposure on spontaneous alternation, anxiety, motor co-ordination and locomotor activity of adult wistar rats and viability of C6 (Glial) cells in culture.

The effects of ELF-PEMF exposure on spontaneous alternation, anxiety, motor coordination, and locomotor activity have been discussed in various pre-clinical and clinical settings. Several epidemiological and experimental studies have demonstrated the potential effects of ELF-PEMF when exposed > âˆ¼1 h/day; however, very few studies have focused on understanding the influence of ELF-PEMF exposure of 1-3 mT with an exposure duration of < 1 h/day on spontaneous alternation, anxiety, motor coordination, and locomotor activity. Hence, we attempted to study the effects of ELF-PEMF exposure of 1-3 mT, 50 Hz with an exposure duration of 20 min each with a 4 h gap (2 times) on the cellular proliferation and morphologies of C6 (Glial) cells and spontaneous alternation, anxiety, motor coordination and locomotor activity of Wistar rats under in vitro and in vivo conditions, respectively. The results showed that ELF-PEMF exposure did not induce any significant levels of cellular fragmentation and changes in the morphology of glial cells. Also, the outcomes revealed no noticeable effects on spontaneous alternation, anxiety, motor coordination, and locomotor activity in PEMF-exposed groups compared with the control. No undesirable side effects were observed at the highest dose (B=3 mT). We also performed histological analysis of the selected brain sections (hippocampus and cortex) following ELF-PEMF exposure. Incidentally, no significant changes were observed in cortical cell counts, tissue structure, and morphology.

A Fully Validated UHPLC-MS/MS Method for the Estimation of Pimavanserin in Human (K2EDTA) Plasma and its Application to a Clinical Pharmacokinetic Study.

A simple, fast and extremely sensitive for estimating Pimavanserin in human (K2EDTA) plasma using ultra high-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) was newly developed and validated. Sample extraction was accomplished using a partition liquid extraction (LLE-liquid-liquid extraction) procedure utilizing extraction solvent, methyl tertiary butyl ether. Separation of the components, chromatography, was done using a C18 chromatographic analytical column employing acetonitrile:methanol: 0.1% formic acid solution (40:40:20 volume by volume) pumped with 0.800 mL/min as the flow rate. For Pimavanserin, the established methodology was linear throughout the calibration curve range from 0.25ng/mL till 50.0 ng/mL. Results of intraday and interday accuracy and precision of Pimavanserin met recent regulatory requirements. This methodology was effectively used to estimate Pimavanserin in vivo human (K2EDTA) plasma concentration for a clinical pharmacokinetic study.

Comparative Evaluation of Effectiveness of 2% Lignocaine Hydrochloride with Clonidine Hydrochloride versus 2% Lignocaine Hydrochloride with Adrenaline Bitartrate as Local Anesthetic for Adult Patients Undergoing Surgical Extraction of Impacted Mandibular Third Molars: A Randomized Controlled Clinical Study.

BACKGROUND AND OBJECTIVES: Clonidine is a common additive to local anesthetics for various regional and local nerve blocks. However, its effectiveness in dentistry has not yet been fully explored. Thus, this study was performed to evaluate the quality of anesthesia, vasoconstrictive effects, hemodynamic response, and pain control using a solution of 2% lignocaine hydrochloride with clonidine hydrochloride in comparison with the standard solution of 2% lignocaine hydrochloride and adrenaline bitartrate for pterygomandibular nerve blocks. MATERIALS AND METHODS: A parallel arm, triple-blind randomized controlled study was conducted on 152 patients belonging to ASA-I (American Society of Anesthesiologists) category in the age group of 18-45 years, requiring surgical extraction of impacted mandibular third molars. The patients were divided equally into two groups randomly by computer-generated sequence; Group 1: 2% lignocaine hydrochloride with 1 ml of clonidine hydrochloride (150 µg/ml) and Group 2: 2% lignocaine hydrochloride with adrenaline bitartrate 1: 80,000 (12.5 µg/ml). The variables evaluated were systolic, diastolic, and mean arterial blood pressures, heart rate (HR), blood loss, onset, depth (pain), and duration of anesthesia. RESULTS: There was a statistically nonsignificant difference seen between the two groups (P > 0.05) for the onset of anesthesia, pain assessed, and blood loss, whereas a statistically highly significant difference was seen for cardiovascular variables (systolic, diastolic and mean arterial blood pressures, and HR) at various intervals with higher values for Group 2 (P < 0.001) and for the duration of action of local anesthesia (LA), with higher values for Group 1 (P < 0.001). CONCLUSIONS: Clonidine as an additive to lignocaine has proved to have the onset of action, vasoconstrictive properties, and pain control, equivalent to adrenaline. However, with better stability of hemodynamic variables and prolonged duration of action of LA with clonidine, it can be considered as a better, safer, and more effective additive to lignocaine than adrenaline.

Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology. Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy.

Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO2 nanowired BF 2649 (1mg/kg, i.p.) or CLBPT (1mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25µL) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier.

Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51.

Military personnel are often exposed to high altitude (HA, ca. 4500-5000m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier.

Superior antioxidant and anti-ischemic neuroprotective effects of cerebrolysin in heat stroke following intoxication of engineered metal Ag and Cu nanoparticles: A comparative biochemical and physiological study with other stroke therapies.

Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat stroke intoxicated with NPs. In this investigation neuroprotective effects of cerebrolysin, a balanced composition of several neurotrophic factors and active peptides fragments exhibiting powerful antioxidant and anti-ischemic effects was examined in heat stroke after NPs intoxication. In addition, its efficacy is compared to currently used drugs in post-stroke therapies in clinics. Thus, levertiracetam, pregabalin, topiramat and valproate were compared in standard doses with cerebrolysin in heat stroke intoxicated with Cu or Ag NPs (50-60nm, 50mg/kg, i.p./day for 7 days). Rats were subjected to 4h heat stress (HS) in a biological oxygen demand incubator at 38°C (Relative Humidity 45-47%; Wind velocity 22.4-25.6cm/s) that resulted in profound increase in oxidants Luminol, Lucigenin, Malondialdehyde and Myeloperoxidase, and a marked decrease in antioxidant Glutathione. At this time severe reductions in the cerebral blood flow (CBF) was seen together with increased blood-brain barrier (BBB) breakdown and brain edema formation. These pathophysiological responses were exacerbated in NPs treated heat-stressed animals. Pretreatment with cerebrolysin (2.5mL/kg, i.v.) once daily for 3 days significantly attenuated the oxidative stress, BBB breakdown and brain edema and improved CBF in the heat stressed group. The other drugs were least effective on brain pathology following heat stroke. However, in NPs treated heat stressed animals 5mL/kg conventional cerebrolysin and 2.5mL/kg nanowired cerebrolysin is needed to attenuate oxidative stress, BBB breakdown, brain edema and to improve CBF. Interestingly, the other drugs even in higher doses used are unable to alter brain pathologies in NPs and heat stress. These observations are the first to demonstrate that cerebrolysin is the most superior antioxidant and anti-ischemic drug in NPs exposed heat stroke, not reported earlier.

Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology.

Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50-60nm) nanoparticles (50mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1µg/kg, i.v. but not 0.5µg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier.

Understanding Nanotechnology in the Treatment of Oral Cancer: A Comprehensive Review.

Oral cancer is the 11th most common cancer in the world with a high morbidity rate. Various conventional therapies have been used for the treatment of oral cancer such as surgery, radiotherapy, and chemotherapy used either alone or in combination but these have many limitations, making them unsuitable for treating oral cancer. Nanotechnology has been emerged out as an innovative tool in the field of oral cancer which has proved to provide effective results overcoming the limitations of conventional drug therapies. This system involves a nanoparticle drug delivery system based on a targeted therapy in which therapeutic drugs or agents act on the targeted cells without affecting normal healthy cells. Literature has shown that several nanoparticles, organic and inorganic nanoparticles, have been used as the drug delivery system in different types of oral cancers such as oral squamous cell carcinoma, cancer of the tongue, head, and neck cancers. Drugs like cisplatin, 5-fluorouracil, methotrexate, doxorubicin, etc., when coated with nano-polymers have shown better results compared with conventional drugs in oral cancer. Other nanoparticles such as liposomes, hydrogels, nanodiamonds, carbon rods, etc. have also been used with minimal side effects. This paper aims to review and discuss various nanotechnology systems in the field of oral cancer and to evaluate the efficacy of these systems in treating oral cancer compared with conventional drug delivery methods.

Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide.

Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑßP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier.

Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury.

Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224N results in profound progressive functional deficit, memory impairment and brain pathology from 5h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

Nanodelivery of traditional Chinese Gingko Biloba extract EGb-761 and bilobalide BN-52021 induces superior neuroprotective effects on pathophysiology of heat stroke.

Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic strategies is needed to induce neuroprotection in HS. Extracts of Gingko Biloba (EGb-761) is traditionally used in a variety of mental disorders in Chinese traditional medicine since ages. In this chapter, effects of TiO2 nanowired EGb-761 and BN-52021 delivery to treat brain pathologies in HS is discussed based on our own investigations. We observed that TiO2 nanowired delivery of EGb-761 or TiO2 BN-52021 is able to attenuate more that 80% reduction in the brain pathology in HS as compared to conventional drug delivery. The functional outcome after HS is also significantly improved by nanowired delivery of EGb-761 and BN-52021. These observations are the first to suggest that nanowired delivery of EGb-761 and BN-52021 has superior therapeutic effects in HS not reported earlier. The clinical significance in relation to the military medicine is discussed.

Upregulation of hemeoxygenase enzymes HO-1 and HO-2 following ischemia-reperfusion injury in connection with experimental cardiac arrest and cardiopulmonary resuscitation: Neuroprotective effects of methylene blue.

Oxidative stress plays an important role in neuronal injuries after cardiac arrest. Increased production of carbon monoxide (CO) by the enzyme hemeoxygenase (HO) in the brain is induced by the oxidative stress. HO is present in the CNS in two isoforms, namely the inducible HO-1 and the constitutive HO-2. Elevated levels of serum HO-1 occurs in cardiac arrest patients and upregulation of HO-1 in cardiac arrest is seen in the neurons. However, the role of HO-2 in cardiac arrest is not well known. In this review involvement of HO-1 and HO-2 enzymes in the porcine brain following cardiac arrest and resuscitation is discussed based on our own observations. In addition, neuroprotective role of methylene blue- an antioxidant dye on alterations in HO under in cardiac arrest is also presented. The biochemical findings of HO-1 and HO-2 enzymes using ELISA were further confirmed by immunocytochemical approach to localize selective regional alterations in cardiac arrest. Our observations are the first to show that cardiac arrest followed by successful cardiopulmonary resuscitation results in significant alteration in cerebral concentrations of HO-1 and HO-2 levels indicating a prominent role of CO in brain pathology and methylene blue during CPR followed by induced hypothermia leading to superior neuroprotection after return of spontaneous circulation (ROSC), not reported earlier.

Retraction notice to "Melatonin renders neuroprotection by protein kinase C mediated aquaporin-4 inhibition in animal model of focal cerebral ischemia" [Life Sci. 100 (2014) 97-109].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Panels from Figures 2a and 3a appear similar to panels from Figures 2A and 3A of the article that the authors et al. have previously published in PLoS One 8(9) (2013) e73481 https://doi.org/10.1371/journal.pone.0073481 and Figures 1c and 2c of the article that Vikas Mishra, Rajkumar Verma and Ram Raghubir have published in Neuropharmacology 59 (2010) 582-588 https://doi.org/10.1016/j.neuropharm.2010.08.015. One of the conditions of submission of a paper for publication is that authors declare explicitly that the work is original. Re-use of any data should be appropriately cited. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Analysis of Clinical Trial Registry of India for Evidence of Anti-Arthritic Properties of Withania somnifera (Ashwagandha).

BACKGROUND: Withania somnifera (Ashwagandha) is an herb with anti-inflammatory properties used in managing arthritis. There is significant clinical data in the public domain on the effects of Ashwagandha and this study was aimed at compiling and analysing these data in a structured manner. The major sources of evidence data were clinical trials and systematic review of extant literature. METHODOLOGY: Retrospective database search was conducted in the Clinical Trial Registry of India for trials registered from April 2008 to March 2020, and published literature related to the anti-arthritic effects of Withania somnifera were reviewed. RESULTS: In all, 77 registered clinical trials were analysed and common among them were interventional, single-centre, randomized, double-blind, two-arm studies with Placebo being the comparator. Similar findings were observed in the 10 published clinical trials on arthritis evaluated for this study. While industry- and government-sponsored trials were identified, government funded sites with approvals from Institutional Ethics Committees were preferred. Most trials were registered as Phase 2 with the highest number of sites in the state of Maharashtra. The solid dosage form was most preferred. CONCLUSION: While the effects of Withania somnifera on various disorders are being investigated by several clinical trials, the ones evaluated for this study provide insight on its potential in managing arthritis when given for a specific duration. Evidence shows a dosage of 6 gm in powder form or extracts in tablets, or 500 -1000 mg capsule consumed for a duration of 8 - 12 weeks may be useful in managing symptoms of arthritis in patients.

Concussive head injury exacerbates neuropathology of sleep deprivation: Superior neuroprotection by co-administration of TiO2-nanowired cerebrolysin, alpha-melanocyte-stimulating hormone, and mesenchymal stem cells.

Sleep deprivation (SD) is common in military personnel engaged in combat operations leading to brain dysfunction. Military personnel during acute or chronic SD often prone to traumatic brain injury (TBI) indicating the possibility of further exacerbating brain pathology. Several lines of evidence suggest that in both TBI and SD alpha-melanocyte-stimulating hormone (α-MSH) and brain-derived neurotrophic factor (BDNF) levels decreases in plasma and brain. Thus, a possibility exists that exogenous supplement of α-MSH and/or BDNF induces neuroprotection in SD compounded with TBI. In addition, mesenchymal stem cells (MSCs) are very portent in inducing neuroprotection in TBI. We examined the effects of concussive head injury (CHI) in SD on brain pathology. Furthermore, possible neuroprotective effects of α-MSH, MSCs and neurotrophic factors treatment were explored in a rat model of SD and CHI. Rats subjected to 48h SD with CHI exhibited higher leakage of BBB to Evans blue and radioiodine compared to identical SD or CHI alone. Brain pathology was also exacerbated in SD with CHI group as compared to SD or CHI alone together with a significant reduction in α-MSH and BDNF levels in plasma and brain and enhanced level of tumor necrosis factor-alpha (TNF-α). Exogenous administration of α-MSH (250µg/kg) together with MSCs (1×106) and cerebrolysin (a balanced composition of several neurotrophic factors and active peptide fragments) (5mL/kg) significantly induced neuroprotection in SD with CHI. Interestingly, TiO2 nanowired delivery of α-MSH (100µg), MSCs, and cerebrolysin (2.5mL/kg) induced enhanced neuroprotection with higher levels of α-MSH and BDNF and decreased the TNF-α in SD with CHI. These observations are the first to show that TiO2 nanowired administration of α-MSH, MSCs and cerebrolysin induces superior neuroprotection following SD in CHI, not reported earlier. The clinical significance of our findings in light of the current literature is discussed.

Co-administration of TiO2-nanowired dl-3-n-butylphthalide (dl-NBP) and mesenchymal stem cells enhanced neuroprotection in Parkinson's disease exacerbated by concussive head injury.

dl-3-n-butylphthalide (dl-NBP) is a powerful antioxidant compound with profound neuroprotective effects in stroke and brain injury. However, its role in Parkinson's disease (PD) is not well known. Traumatic brain injury (TBI) is one of the key factors in precipitating PD like symptoms in civilians and particularly in military personnel. Thus, it would be interesting to explore the possible neuroprotective effects of NBP in PD following concussive head injury (CHI). In this chapter effect of nanowired delivery of NBP together with mesenchymal stem cells (MSCs) in PD with CHI is discussed based on our own investigations. It appears that CHI exacerbates PD pathophysiology in terms of p-tau, α-synuclein (ASNC) levels in the cerebrospinal fluid (CSF) and the loss of TH immunoreactivity in substantia niagra pars compacta (SNpc) and striatum (STr) along with dopamine (DA), dopamine decarboxylase (DOPAC). And homovanillic acid (HVA). Our observations are the first to show that a combination of NBP with MSCs when delivered using nanowired technology induces superior neuroprotective effects in PD brain pathology exacerbated by CHI, not reported earlier.