Browsing by Author "Kumar, Puneet"

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    Animal models of attention-deficit hyperactivity disorder (ADHD)
    (John Wiley and Sons Inc, 2021-01-15T00:00:00) Rahi, Vikrant; Kumar, Puneet
    Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder characterized by three primary symptoms hyperactivity, attention deficit, and impulsiveness, observed in both children and adults. In childhood, this disorder is more common in boys than in girls, and at least 75% will continue to suffer from the disorder until adulthood. Individuals with ADHD generally have poor academic, occupational, and social functioning resulting from developmentally inappropriate levels of hyperactivity and impulsivity, as well as impaired ability to maintain attention on motivationally relevant tasks. Very few drugs available in clinical practice altogether abolish the symptoms of ADHD, therefore, to find new drugs and target it is essential to understand the neuropathological, neurochemical, and genetic alterations that lead to the progression of ADHD. With this contrast, an animal study is the best approach because animal models provide relatively fast invasive manipulation, rigorous hypothesis testing, as well as it provides a better angle to understand the pathological mechanisms involved in disease progression. Moreover, animal models, especially for ADHD, serve with good predictive validity would allow the assessment and development of new therapeutic interventions, with this aim, the present review collect the various animal models on a single platform so that the research can select an appropriate model to pursue his study. � 2021 International Society for Developmental Neuroscience
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    Animal models of Huntington�s disease and their applicability to novel drug discovery and development
    (Taylor and Francis Ltd., 2023-04-12T00:00:00) Upadhayay, Shubham; Jamwal, Sumit; Kumar, Puneet
    Introduction: Huntington�s disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the CAG trinucleotide repeat in huntingtin (Htt) gene. The discovery of the HD-causing gene prompted the creation of new HD animal models, proving that mutations in the HD gene are linked to either loss of function of the wild-type (un-mutated) gene or toxic gain in the function of a mutated gene. Areas Covered: Animal models of HD have led to an increased understanding of its pathogenesis and resulted in the discovery of new therapeutic targets/drugs. The focus of this review is on the selection and validation of animal models for HD drug discovery. Furthermore, several drugs tested using various models in the preclinical phase have been compiled to demonstrate the applicability of these HD animal models. Expert opinion: The applicability of animal models for HD drug discovery has been well demonstrated. Nevertheless, despite the enormous progression made to date, the development of drug therapy to completely alleviate disease progression has not been achieved. Most of the pre-clinically tested drugs have shown promising results in alleviating HD-associated neurodegeneration and motor and non-motor symptoms, but only a few of them thrived to produce satisfactory results in the clinical phase. This failure has raised concerns about the selection of HD animal models and species, and new strategies for selection are mandated. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Bacillus calmette gaurine vaccine ameliorates the neurotoxicity of quinolinic acid in rats via the modulation of antioxidant, inflammatory and apoptotic markers
    (Elsevier B.V., 2023-05-11T00:00:00) Yedke, Narhari Gangaram; Arthur, Richmond; Kumar, Puneet
    A mutation in the Huntingtin gene causes �Huntington's disease, which presents as a motor and behavioral impairment. Due to the limited drug therapy for this disease, scientists are constantly searching for newer and alternative drugs that may either retard or prevent the progress of the disease. This study aims to explore the neuroprotective potential of Bacillus Calmette Gaurine (BCG) vaccine against quinolinic acid-induced (QA) neurotoxicity in rats. QA (200 nmol/2 �l, i.s) was injected bilaterally into the rat striatum, after which a single dose of BCG (2 � 10^7, cfu) was given to the rats. Animals were assessed for behavioral parameters on the 14th and 21st days. On the 22nd day, animals were sacrificed, brains were harvested, and striatum was separated to evaluate biochemical, inflammatory, and apoptotic mediators. Histopathological studies were performed using Hematoxyline and Eosin staining to assess neuronal morphology. BCG treatment reversed motor abnormalities, reduced oxidative stress and neuroinflammatory markers, apoptotic mediators and striatal lesions induced by QA treatment. In conclusion, treat' 'ing rats with BCG vaccine (2 � 10^7, cfu) mitigated the quinolinic acid-induced Huntington's disease-like symptoms. Hence, BCG vaccine (2 �10^7, cfu) could be used as an adjuvant in managing HD. � 2023 Elsevier B.V.
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    Bacillus Calmette-Gu�rin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats
    (2023-11-20T00:00:00) Yedke, Narhari Gangaram; Upadhayay, Shubham; Singh, Randhir; Jamwal, Sumit; Ahmad, Sheikh F.; Kumar, Puneet
    Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 � 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.
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    The beneficial effect of rice bran extract against rotenone-induced experimental parkinson�s disease in rats
    (Bentham Science Publishers, 2021-02-12T00:00:00) Kumar, Sachin; Kumar, Puneet
    Background: Neurodegenerative diseases have become an increasing cause of various disabilities worldwide, followed by aging, including Parkinson�s disease (PD). Parkinson�s disease is a degenerative brain disorder distinguished by growing motor & non-motor failure due to the de-generation of medium-sized spiked neurons in the striatum region. Rotenone is often employed to originate the animal model of PD. It is a powerful blocker of mitochondrial complex-I, mitochon-drial electron transport chain that reliably produces Parkinsonism-like symptoms in rats. Rice bran (RB) is very rich in polyunsaturated fatty acids (PUFA) and nutritionally beneficial compounds, such as ?-oryzanol, tocopherols, and tocotrienols and sterols are believed to have favorable out-comes on oxidative stress & mitochondrial function. Objective: The present study has been designed to explore RB extract�s effect against rotenone-in-duced neurotoxicity in rats. Methods: In the present study, Rotenone (2 mg/kg, s.c) was administered systemically for 28 days. The hexane extract of RB was prepared using Soxhlation. Hexane extract (250 & 500 mg/kg) was administered per oral for 28 days in rotenone-treated groups. Behavioral parameters (grip strength, motor coordination, locomotion, and catalepsy) were conducted on the 7th, 14th, 21st, and 28th day. Animals were sacrificed on the 29th day for biochemical estimation in the striatum and cortex. Results: This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration, and decreased glutathione, catalase, SOD) in rotenone-treated animals. Administration of hexane extract of RB prevented the behavioral, biochemical alterations induced by rotenone. The current research has been sketched to inspect RB ex-tract�s effect against rotenone-developed neurotoxicity in rats. Conclusion: The findings support that PD is associated with impairments in motor activity. The results also suggest that the nutraceutical rice bran that contains ?-oryzanol, Vitamin-E, ferulic acid etc., may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats. � 2021 Bentham Science Publishers.
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    Berberine Ameliorate Haloperidol and 3-Nitropropionic Acid-Induced Neurotoxicity in Rats
    (Springer, 2022-07-25T00:00:00) Kadir, Abdul; Singh, Jasdeep; Rahi, Vikrant; Kumar, Puneet
    Berberine due to its antioxidant properties, has been used around the globe significantly to treat several brain disorders. Also, oxidative stress is a pathological hallmark in neurodegenerative diseases like Huntington�s disease (HD) and Tardive dyskinesia (TD). Berberine an alkaloid from plants has been reported to have neuroprotective potential in several animal models of neurodegenerative diseases. Hence, this study aims to evaluate the neuroprotective effect of berberine in the animal model of 3-nitropropionic acid (3-NP) induced HD and haloperidol induced tardive dyskinesia with special emphasis on its antioxidant property. The study protocol was divided into 2 phases, first phase involved the administration of 3-NP and berberine at the dose of (25, 50, and 100�mg/kg) intraperitoneally (i.p) and orally (p.o.) respectively for 21�days, and the following parameters (rotarod, narrow beam walk and photoactometer) as a measure of motor activity and striatal and cortical levels of (LPO, GSH, SOD, catalase, and nitrate) evaluated as a measure of oxidative stress were assessed for HD. Similarly in the second phase, TD was induced by using haloperidol, for 21�days and berberine at the dose of (25, 50, and 100�mg/kg) was administered, and both physical and biochemical parameters were assessed as mentioned for the HD study. The resultant�data indicated that berberine attenuate 3-NP and haloperidol-induced behavioral changes and improved the antioxidant capcity in rodents. Hence berberine might be a novel therapeutic candidate to manage TD & HD. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Calcium channelopathies in neurodegenerative disorder: an untold story of RyR and SERCA
    (Taylor and Francis Ltd., 2023-11-16T00:00:00) Dhureja, Maanvi; Arthur, Richmond; Soni, Divya; Upadhayay, Shubham; Temgire, Pooja; Kumar, Puneet
    Introduction: Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously undiscovered tale focusing on the Ryanodine Receptor (RyR) and the Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA). Calcium signaling mainly orchestrates neural communication, which regulates synaptic transmission and total network activity. It has been determined that RyR play a significant role in managing neuronal functions, most notably in releasing intracellular calcium from the endoplasmic reticulum. Areas covered: It highlights the involvement of calcium channels such as RyR and SERCA in physiological and pathophysiological conditions. Expert opinion: Links between RyR and SERCA activity dysregulation, aberrant calcium levels, motor and cognitive dysfunction have brought attention to the importance of RyR and SERCA modulation in neurodegenerative disorders. Understanding the obscure function of these proteins will open up new therapeutic possibilities to address the underlying causes of neurodegenerative diseases. The unreported RyR and SERCA narrative broadens the understanding of calcium channelopathies in movement disorders and calls for more research into cutting-edge therapeutic approaches. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Ferulic acid ameliorates neurodegeneration via the Nrf2/ARE signalling pathway: A Review
    (Elsevier B.V., 2022-10-30T00:00:00) Singh, Surbhi; Arthur, Richmond; Upadhayay, Shubham; Kumar, Puneet
    Background: Ferulic acid is a polyphenolic phytoconstituent synthesized from the metabolism of amino acids phenylalanine and tyrosine found in fruits and vegetables. Neurodegenerative disorders have been a thorn in the flesh of neuroscientists owing in part to the increase in the aged population. Several drugs used in the management of these disorders are either ineffective or come with unbearable side effects. We present a review of ferulic acid focusing on leveraging its antioxidant property in an attempt to explain its role in neurodegenerative disorders. Basic procedure: data were obtained by perusing scientific databases including Web of Science and PubMed. It was realised that 18,000 articles were associated with ferulic acid from 1960-to 2022. We narrowed it down using the keywords neuroprotection, and antioxidant of which we had 239 articles. Main findings: results indicated that ferulic acid has wide neuropharmacological applications due to its antioxidant, anti-inflammatory, neuroprotective and antiapoptotic effects among others. The neuroprotective effect of ferulic acid has been studied in many diseases like Alzheimer's, Epilepsy, and Parkinson's disease. Principal conclusion: the neuroprotective potential of FA may be due to its ability to absorb active forms of oxygen and nitrogen and use redox-bearing compounds to regulate genetic expression including, encoding for antioxidant enzymes, the anti-apoptotic protein family Bcl-2, and pro-survival neurotrophic factors like BDNF. Its higher bioavailability and lipophilic nature make it a better drug candidate than other polyphenols for neurological disorders. � 2022 The Author(s)
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    Filgrastim, a Recombinant Form of Granulocyte Colony-stimulating Factor, Ameliorates 3-nitropropionic Acid and Haloperidol-induced Striatal Neurotoxicity in Rats
    (Springer, 2022-11-17T00:00:00) Rahi, Vikrant; Ram, Parladh; Kumar, Puneet
    Striatal neurotoxicity is the pathological hallmark for a heterogeneous group of movement disorders like Tardive dyskinesia (TD) and Huntington�s disease (HD). Both diseases are characterized by progressive impairment in motor function. TD and HD share common features at both cellular and subcellular levels. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor (GCSF), shows neuroprotective properties in in-vivo models of movement disorders. This study seeks to evaluate the neuroprotective effect of filgrastim in haloperidol and 3-NP-induced neurotoxicity in rats. The study was divided into two: in study one, rats were administered with haloperidol for 21�days, filgrastim at the dose of (20, 40, 60��g/kg,s.c.) was administered once a day before haloperidol treatment and the following parameters (orofacial movements, rotarod, actophotometer) were performed to assess TD. Similarly, in the second study, rats were administered with 3-NP for 21�days, filgrastim at a dose of (20 and 40��g/kg, s.c.) was administered, and the following parameters (rotarod, narrow beam walk, and open field test) were assessed for HD. On the 22nd day, animals were sacrificed and cortex and striatum isolated for oxidative stress (LPO, GSH, SOD, catalase, and nitrate) marker assessment. Results revealed that haloperidol and 3-NP treatment significantly impaired motor coordination, and oxidative defense inducing TD and HD-like symptoms. Treatment with filgrastim significantly averted haloperidol and 3-NP-induced behavioral and biochemical alterations. Conclusively, the neuroprotective effect of filgrastim is credited to its antioxidant properties. Hence, filgrastim might be a novel therapeutic candidate for the management of TD and HD. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    GSK-3?-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders
    (Springer Science and Business Media Deutschland GmbH, 2022-07-27T00:00:00) Soni, Divya; Kumar, Puneet
    Movement disorders are neurological conditions characterized by involuntary motor movements, such as dystonia, ataxia, chorea myoclonus, tremors, Huntington�s disease (HD), and Parkinson�s disease (PD). It is classified into two categories: hypokinetic and hyperkinetic movements. Globally, movement disorders are a major cause of death. The pathophysiological process is initiated by excessive ROS generation, mitochondrial dysfunction, neuroinflammation, and neurotransmitters imbalance that lead to motor dysfunction in PD and HD patients. Several endogenous targets including Nrf2 maintain oxidative balance in the body. Activation of Nrf2 signaling is regulated by the enzyme glycogen synthase kinase (GSK-3?). In the cytoplasm, inhibition of GSK-3? regulates cellular proliferation, homeostasis, and apoptotic process by stimulating the nuclear factor erythroid 2 (Nrf2) pathway which is involved in the elevation of the cellular antioxidant enzymes which controls the ROS generation. The activation of Nrf2 increases the expression of antioxidant response elements (ARE), such as (Hemeoxygenase-1) HO-1, which decreases excessive cellular stress, mitochondrial dysfunction, apoptosis, and neuronal degeneration, which is the major cause of motor dysfunction. The present review explores the GSK-3?-mediated neuroprotection in various movement disorders through the Nrf2/HO-1 antioxidant pathway. This review provides a�link between GSK-3? and the Nrf2/HO-1 signaling pathway in the treatment of PD and HD. In addition to that it highlights various GSK-3? inhibitors and the Nrf2/HO-1 activators, which exert robust neuroprotection against motor disorders. Therefore, the present review will help in the discovery of new therapy for PD and HD patients. � 2022, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.
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    Impact of noscapine on halting the progression of pentylenetetrazole induced kindling epilepsy in mice
    (John Wiley and Sons Inc, 2023-09-19T00:00:00) Gupta, Rishav; Soni, Divya; Upadhayay, Shubham; Dhureja, Maanvi; Kumar, Puneet
    Epilepsy is caused by an excessive recurrent excitatory neuronal firing, characterized by motor, psychomotor, and sensory impairments. Current therapies fail to produce 100% outcomes because of the complexity of the disease, poor diagnosis, and upsurge�to drug-resistant epilepsy. The study repurposed�the drug �noscapine��mainly known for its anti-tussive properties. For the management of epilepsy and its associated secondary complications. To confirm the effect of noscapine, adult mice were injected with pentylenetetrazole (PTZ) (35 mg/kg i.p.) on an alternate day for 29 days to induce epilepsy. Animals were pretreated with noscapine in three doses (5, 10, and 20 mg/kg i.p.) for 33 days. Various behavioural assessments like the open field test, Morris water maze, and tail suspension test were performed to observe animals' locomotor activity, spatial memory, and anxiety-depressive behaviour. On the 34th day, animals were sacrificed, and brains were removed for biochemical estimations. Prolonged PTZ treatment reduced locomotor, learning activity, and increased anxiety-depressive behaviour, which was further confirmed by reduced antioxidant levels such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase because of increased oxido-nitrosative stress, that is, malondialdehyde (MDA) and nitrite in the brain. In comparison, noscapine pretreatment attenuated PTZ-induced behavioural and biochemical changes in the animals. The results indicate that noscapine ameliorates the oxido-nitrosative stress. However, studies indicate that oxido-nitrosative stress is a significant concern for the GABAergic neurons and promotes the disease progression. Further studies are required to explore the molecular mechanism of noscapine, which might be a practical approach as a newer antiepileptic agent. � 2023 John Wiley & Sons Australia, Ltd.
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    Involvement of the G-Protein-Coupled Estrogen Receptor-1 (GPER) Signaling Pathway in Neurodegenerative Disorders: A Review
    (Springer, 2022-10-28T00:00:00) Upadhayay, Shubham; Gupta, Rishav; Singh, Surbhi; Mundkar, Maroti; Singh, Gursewak; Kumar, Puneet
    The G-protein-coupled estrogen receptor-1 (GPER) is an extranuclear estrogen receptor that regulates the expression of several downstream signaling pathways with a variety of biological actions including cell migration, proliferation, and apoptosis in different parts of the brain area. It is endogenously activated by estrogen, a steroidal hormone that binds to GPER receptors which help in maintaining cellular homeostasis and neuronal integrity as well as influences neurogenesis. In contrast, neurodegenerative disorders are a big problem for society, and still many people suffer from motor and cognitive impairments. Research to date reported that GPER has the potential to whittle down motor abnormalities and cognitive dysfunction by limiting the progression of neurodegenerative disorders. Although several findings suggest that GPER activation accelerated transcription of the PI3K/Akt/Gsk-3? and ERK1/2 signaling pathway that halt disease progression by decreasing oxidative stress, neuroinflammation, and apoptosis. Accordingly, the goal of this review is to highlight the basic mechanism of GPER signaling pathway-mediated neuroprotection in various neurodegenerative disorders including Parkinson�s disease (PD), Huntington�s disease (HD), Tardive dyskinesia (TD), and Epilepsy. This review also discusses the role of the GPER activators which might be a promising therapeutic target option to treat neurodegenerative disorders. All the data were obtained from published articles in PubMed (353), Web of Science (788), and Scopus (770) databases using the search terms: GPER, PD, HD, TD, epilepsy, and neurodegenerative disorders. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Monkeypox infection: The past, present, and future
    (Elsevier B.V., 2022-10-29T00:00:00) Upadhayay, Shubham; Arthur, Richmond; Soni, Divya; Yadav, Poonam; Navik, UmaShanker; Singh, Randhir; Gurjeet Singh, Thakur; Kumar, Puneet
    Monkeypox is a zoonotic illness caused by the monkeypox virus (MPXV) that has a similar etiology to smallpox. The first case of monkeypox was reported in Western and Central Africa in 1971, and in 2003, there was an outbreak of monkeypox viruses outside Africa. According to the World Health Organization (WHO) and Center for Disease Control and Prevention (CDC), monkeypox is transmitted through direct contact with infected animals or persons exposed to infectious sores, scabs, or body fluids. Also, intimate contact between people during sex, kissing, cuddling, or touching parts of the body can result in the spreading of this disease. The use of the smallpox vaccine against monkeypox has several challenges and hence anti-virals such as cidofovir, brincidofovir, and tecovirimat have been used for the symptomatic relief of patients and reversing the lesion formation on the skin. Despite the recent outbreak of monkeypox most especially in hitherto non-endemic countries, there is still a lack of definitive treatment for monkeypox. In the present review, emphasis was focused on etiopathology, transmission, currently available therapeutic agents, and future targets that could be explored to halt the progression of monkeypox. From our review we can postulate that owing to the lack of a definitive cure to this reemerging disorder, there is a need for general awareness about the transmission as well as to develop appropriate diagnostic procedures, immunizations, and antiviral medication. � 2022 Elsevier B.V.
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    Natural Products as an Alternative Therapy for Brain Tumors: From Bench To Bedside
    (Springer Singapore, 2022-09-28T00:00:00) Kumar, Sachin; Kumar, Mandeep; Bijalwan, Anjali; Sharma, Shubham; Kumar, Puneet
    Incremental elevation in the trends of a brain tumor in recent years accounts for 5% adult population, whereas the number exceeds 70% in the case of children. Evidence reveals an eventual metastasize of 20%-30% of malignant tumors to the brain�s different regions. Compression in the brain tissue and elevated intracranial pressure mediated by benign and malignant tumors contributed to severe consequences like the central nervous system (CNS) damage or even imperil the patient�s life. Despite multiple therapeutic strategies in the market, none of the drugs are fully effective and safe. Strategic advancement indicates chemotherapy as a treatment of choice for critical conditions like brain tumors, but the chemotherapy drugs toxicity is still a major therapeutic hurdle. Plants and their derived natural products are one of the most emerging targets to strike against brain tumors. Analogs of several natural products are already demonstrated as antitumor in nature, and day by day, advancements unfold various other plant and plant derivatives having such antitumor activity. This chapter aims to underline and emphasize the antitumor agents, which can target brain tumors procured from the natural origin such as natural products and their analogs. The available data on different plants and isolated compounds of natural origin used to reduce and arrest brain tumors is also discussed here. � Springer Nature Singapore Pte Ltd. 2022.
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    Neurobiology of traumatic brain injury
    (Taylor and Francis Ltd., 2021-09-06T00:00:00) Bagri, Kajal; Kumar, Puneet; Deshmukh, Rahul
    Traumatic brain injury (TBI) involves structural damage to the brain regions causing death or disability in patients with lifelong sufferings. Accidental injuries to the brain, besides structural damage, if any, cause activation of various deleterious pathways leading to subsequent neuronal death and permanent dysfunction. However, immediate medical management/treatments could reduce the chances of disability and suffering to the patients. The objective of the current review is to review triggered molecular pathways following TBI and discuss possible targets that could restore brain functions. Understanding the pathologic process is always useful to device novel treatment strategies and may rescue the patient with TBI from death or associated co-morbidities. The current review significantly contributes to improve our understanding about the molecular pathways and neuronal death following TBI and helps us to provide possible targets that could be useful in the management/treatment of TBI. � 2021 Taylor & Francis Group, LLC.
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    Neurodegenerative diseases and brain delivery of therapeutics: Bridging the gap using dendrimers
    (Editions de Sante, 2023-08-26T00:00:00) Kaur, Amandeep; Singh, Navneet; Kaur, Harmanpreet; Kakoty, Violina; Sharma, Deep Shikha; Khursheed, Rubiya; Babu, Molakpogu Ravindra; Harish, Vancha; Gupta, Gaurav; Gulati, Monica; Kumar, Puneet; Dureja, Harish; Alharthi, Nahed S.; Khan, Farhan R.; Rehman, Zia ur; Hakami, Mohammed Ageeli; Patel, Mrunali; Patel, Rashmin; Zandi, Milad; Vishwas, Sukriti; Dua, Kamal; Singh, Sachin Kumar
    Neurodegenerative diseases (NDs) continue to burden human lives and economic conditions. They continue to challenge the healthcare system due to the associated physiological barriers. Traditional treatment approaches are associated with symptomatic relief and are ineffective in the long run. Dendrimers stand out amongst other nanocarriers due to ease of surface modifications, internal encapsulation, and nanoscale uniformity of the molecule. Moreover, their internal core can encapsulate drug through electrostatic interactions. These are stable carriers in the nanometer size range. These either act as therapeutic agents per se or deliver the target drug across the blood-brain barrier while minimizing toxicity. Emerging as a promising non-invasive approach, they demonstrate the capability to interfere with in-vivo protein aggregation, typically associated with neurodegeneration. They assist via exerting various neuroprotective roles, such as in oxidative stress, neuroinflammation, inhibiting certain biochemical parameters, altering protein misfolding and aggregation, etc. However, certain limitations are associated with their elimination and cytotoxicity. The investigation revealed the masking of exposed cationic surfaces of dendrimers with inert substances, such as polyethylene glycol to limit their cytotoxicity. This review describes the incidences and pathophysiology of several NDs, properties, and methods of dendrimer synthesis, followed by various research to explore dendrimers potential to treat NDs. � 2023 Elsevier B.V.
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    Neuroprotection through G-CSF: recent advances and future viewpoints
    (Springer Science and Business Media Deutschland GmbH, 2021-01-02T00:00:00) Rahi, Vikrant; Jamwal, Sumit; Kumar, Puneet
    Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of hematopoietic growth factors, is 19.6�kDa glycoprotein which is responsible for the proliferation, maturation, differentiation, and survival of neutrophilic granulocyte lineage. Apart from its proven clinical application to treat chemotherapy-associated neutropenia, recent pre-clinical studies have highlighted the neuroprotective roles of G-CSF i.e., mobilization of haemopoietic stem cells, anti-apoptotic, neuronal differentiation, angiogenesis and anti-inflammatory in animal models of neurological disorders. G-CSF is expressed by numerous cell types including neuronal, immune and endothelial cells. G-CSF is released in autocrine manner and binds to its receptor G-CSF-R which further activates numerous signaling transduction pathways including PI3K/AKT, JAK/STAT and MAP kinase, and thereby promote neuronal survival, proliferation, differentiation, mobilization of hematopoietic stem and progenitor cells. The expression of G-CSF receptors (G-CSF-R) in the different brain regions and their upregulation in response to neuronal insult indicates the autocrine protective signaling mechanism of G-CSF by inhibition of apoptosis, inflammation, and stimulation of neurogenesis. These observed neuroprotective effects of G-CSF makes it an attractive target to mitigate neurodegeneration associated with neurological disorders. The objective of the review is to highlight and summarize recent updates on G-CSF as a therapeutically versatile neuroprotective agent along with mechanisms of action as well as possible clinical applications in neurodegenerative disorders including AD, PD and HD. � 2021, Maj Institute of Pharmacology Polish Academy of Sciences.
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    Neuroprotective effect of nerolidol in traumatic brain injury associated behavioural comorbidities in rats
    (Oxford University Press, 2020-11-26T00:00:00) Kaur, Amandeep; Jaiswal, Gagandeep; Brar, Jasdeep; Kumar, Puneet
    Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to temporary/permanent secondary injuries, i.e. impairment of cognitive, physical, and psycho-social functions with altered consciousness. The leading mechanism responsible for neuronal damage following TBI is an increase in oxidative reactions initiated by free radicals generated by the injury along with various other mechanisms. Nerolidol is reported to have potent antioxidant and anti-neuroinflammatory properties. The present study was designed to explore the neuroprotective effect of nerolidol in weight-drop-induced TBI in rats. Animals were injured on the 1st day by dropping a free-falling weight of 200 gm from a height of 1 m through a guide pipe onto the exposed skull. After 14 days of injury, nerolidol (25, 50, and 100 mg/kg, i.p.) treatment was given for the next 14 days. Locomotor activity and motor coordination were evaluated using an actophotometer and rotarod, respectively. Cognitive impairment was observed through the Morris Water Maze and Object Recognition Test. On the 29th day, animals were sacrificed, and their brains were collected for the biochemical estimation. The weight drop model significantly decreased locomotor activity, motor coordination, increased Acetylcholinesterase (AChE) activity, oxidative stress, and induced cognitive deficits in TBI rats. Nerolidol significantly improved locomotor activity, reversed motor incoordination and cognitive impairment, and reduced the AChE activity and oxidative/nitrosative stress. The present study demonstrates the promising neuroprotective effects of nerolidol, which might improve the quality of life of TBI patients. � 2021 The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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    Neuroprotective effect of silymarin against 3-Nitropropionic acid-induced neurotoxicity in rats
    (Elsevier B.V., 2022-09-20T00:00:00) Chandolia, Priyanka; Rahi, Vikrant; Kumar, Puneet
    (HD) Huntington's disease is a severe hereditary catastrophic neurological disease with an autosomal dominant heritable changes manifested by cognitive, behavioural, and motor progression deficits, resulting in death. Several mechanisms are involved in the pathogenesis of this complex and rare disease, including excitotoxicity, mitochondrial dysfunction, neurotransmitters imbalance, and oxidative stress. Silymarin was selected as an investigational drug, due to its numerous activities in current research, it possesses substantial antioxidant and neuroprotective functionalities. The present research attempts, i.p. injections of 3-NPA (10 ?mg/kg) were given for 21 days to trigger Huntington-like symptoms in rats. The percentage fluctuations in body weight, the footfall counts, and the time required to transverse the beam and motor functions were analyzed at multiple time points. Oxidative stress markers like MDA/LPO, GSH, protein, nitrite, catalase, and superoxide dismutase levels were examined in the striatum region. The current study results conclusively demonstrate that chronic 3-NPA administration significantly decreased the body weight and showed marked abnormalities in motor coordination, locomotion, and increased striatal generation of free radicals. Furthermore, treatment with silymarin (100 & 200 ?mg/kg/p.o.), mitigated 3-NPA triggered behavioural and biochemical alterations. Our study results could conclude that Silymarin may be advantageous and might develop an adjuvant treatment for the management of Huntington's disease. � 2022 The Authors
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    Neuroprotective potential of Moringa oleifera mediated by NF-kB/Nrf2/HO-1 signaling pathway: A review
    (John Wiley and Sons Inc, 2022-10-07T00:00:00) Mundkar, Maroti; Bijalwan, Anjali; Soni, Divya; Kumar, Puneet
    Moringa oleifera is a traditional Indian herb belonging to the Moringaceae family, it is commonly known as the horse-radish tree, drumstick, or sahajna. In developing countries, Moringa is used as feed for both humans and animals due to its well-known antioxidant, anti-inflammatory, and anti-apoptotic properties owing to its several phytoconstituents including ?-carotene, quercetin, kaempferol, ascorbic acid, flavonoids, phenolic acid, rhamnose, glycosylates, glucomoringin, and isothiocyanates. These constituents help to maintain the brain antioxidant enzyme levels, mitochondrial functions, and neurogenesis, showing neuroprotective effects in several neurodegenerative disorders including Parkinson's Disease, Alzheimer's Disease, Huntington's Disease, and Amyotrophic lateral sclerosis. This review discusses various phytoconstituent of moringa and their therapeutic potential in various neurological disorders. Additionally, we also concise the safety and toxicity profile, of different molecular pathways involved in the neuroprotective effect of M. oleifera including M. oleifera nanoparticles for better therapeutic value. Practical applications: Several clinical and preclinical studies on Moringa oleifera have been conducted, and the outcomes indicate moringa could be used in the treatment of brain disorders. As a result, we conclude that moringa and its nanoformulations could be employed to treat neurological problems. In the future, M. oleifera phytoconstituents could be evaluated against specific signaling pathways, which could aid researchers in discovering their mechanism of action. Furthermore, the use of moringa as a nutraceutical owing to its myriad pharmacological potential will go a long way in boosting the economy of countries that grow moringa on a large scale. � 2022 Wiley Periodicals LLC.