'Comprehensive review of emerging drug targets in traumatic brain injury (TBI): challenges and future scope.

Traumatic brain injury (TBI) is a complex brain problem that causes significant morbidity and mortality among people of all age groups. The complex pathophysiology, varied symptoms, and inadequate treatment further precipitate the problem. Further, TBI produces several psychiatric problems and other related complications in post-TBI survival patients, which are often treated symptomatically or inadequately.

Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer's pathology.

Background: Alzheimer's disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients' functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction.

Safety profile of COVID-19 drugs in a real clinical setting.

Purpose: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has affected millions all over the world and has been declared pandemic, as of 11 March 2020. In addition to the ongoing research and development of vaccines, there is still a dire need for safe and effective drugs for the control and treatment against the SARS-CoV-2 virus infection. Numerous repurposed drugs are under clinical investigations whose reported adverse events can raise worries about their safety.

Neuroprotective effects of roflumilast against quinolinic acid-induced rat model of Huntington's disease through inhibition of NF-κB mediated neuroinflammatory markers and activation of cAMP/CREB/BDNF signaling pathway.

Huntington's disease (HD) is a progressive neurodegenerative and hyperkinetic movement disorder. Decreased activity of cAMP-responsive element-binding protein (CREB) is thought to contribute to the death of striatal medium spiny neurons in HD. The present study has been designed to explore the possible role of roflumilast against qunilonic acid (QA) induced neurotoxicity in rats intending to investigate whether it inhibits the neuroinflammatory response through activation of the cAMP/CREB/BDNF signaling pathway.

Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Its major pathological hallmarks, neurofibrillary tangles (NFT), and amyloid-β plaques can result from dysfunctional insulin signaling. Insulin is an important growth factor that regulates cell growth, energy utilization, mitochondrial function, autophagy, oxidative stress, synaptic plasticity, and cognitive function.

Modeling of antipsychotic-induced metabolic alterations in mice: An experimental approach precluding psychosis as a predisposing factor.

Despite benefits, atypical antipsychotics produce troublesome metabolic adverse effects particularly hyperphagia, weight gain, dyslipidemia, hyperglycemia and insulin resistance which further develop metabolic and cardiac complications. The animal models studied for antipsychotic-induced weight gain only focused on metabolic alteration in antipsychotics treated animals but none has considered psychosis as a predisposing factor which mimics the clinical condition. The present study was aimed to rule out the impact of pharmacologically induced psychosis-like phenotype on metabolic alterations induced by antipsychotics.

Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling.

Background: Obesity is commonly found to be co-morbid with type 2 Diabetes Mellitus. In obese diabetic patients, TLR-2 receptor induced inflammation leads to the development of insulin resistance (IR). Furthermore, the IR is considered to be the most important cause for promoting cognitive decline which is evident in brain of patients with Alzheimer's disease related dementia (ADRD).

Antipsychotics-induced metabolic alterations: Recounting the mechanistic insights, therapeutic targets and pharmacological alternatives.

Atypical antipsychotics (AAPs) are the drug of choice in the management of mental illnesses by virtue of their advantage over typical antipsychotics i.e. least tendency of producing extrapyramidal motor symptoms (EPS) or pseudoparkinsonism.

Protective effects of Spinacia oleracea seeds extract in an experimental model of schizophrenia: Possible behavior, biochemical, neurochemical and cellular alterations.

Schizophrenia is one of the psychotic mental disorders characterized by symptoms of thought, behavior, and social problems. Newer biomedicine and pharmacotherapy has been investigated for the treatment of various neuropsychiatric disorders in the past few decades. Spinacia oleracea is one of these, reported to have beneficial effect against several neurodegenerative disorders.

Neuropathic Pain models caused by damage to central or peripheral nervous system.

Neuropathic Pain (NP) is a painful condition which is a direct consequence of a lesion or disease affecting the somatosensory system with symptoms like allodynia, hyperalgesia. It has complex pathogenesis as it involves several molecular signaling pathways, thus numerous reliable animal models are crucial to understand the underlying mechanism of NP and formulate effective management therapy. Some models like spinal cord injury, chronic constriction injury, spinal nerve ligation, chemotherapy induced peripheral neuropathy, diabetes-induced NP and many more are discussed.

Tramadol ameliorates behavioural, biochemical, mitochondrial and histological alterations in ICV-STZ-induced sporadic dementia of Alzheimer's type in rats.

Alzheimer disease represents a major public health issue with limited therapeutic interventions. We explored the possibility of therapeutic approach by repurposing of tramadol in a sporadic animal model of Alzheimer's type. Streptozocin (STZ 3 mg/kg; bilaterally) was injected to male SD rats through intracerebroventricular (ICV) route.

Ameliorative potential of pioglitazone and ceftriaxone alone and in combination in rat model of neuropathic pain: Targeting PPARγ and GLT-1 pathways.

Background: The relation between glutamate homeostasis and PPAR gamma has got tremendous importance in nerve trauma and pain. Present study has been designed to elucidate the interaction between the GLT-1 activator (ceftriaxone) and PPAR gamma agonist (pioglitazone) in the spinal nerve ligation induced neuropathic pain.

Methods: Male SD rats were subjected to spinal nerve ligation to induce neuropathic pain.

Possible role of P-glycoprotein in the neuroprotective mechanism of berberine in intracerebroventricular streptozotocin-induced cognitive dysfunction.

Rationale: The therapeutic potential of berberine has been well documented in various neurological problems. However, the neurological mechanism of berberine remains untapped in the light of its P-glycoprotein (P-gp)-mediated gut efflux properties responsible for reduced bioavailability. Verapamil, a well known L-type calcium channel blocker, has additional inhibitory activity against P-gp efflux pump.

Improvement of mitochondrial NAD(+)/FAD(+)-linked state-3 respiration by caffeine attenuates quinolinic acid induced motor impairment in rats: implications in Huntington's disease.

Background: Chronic quinolinic acid (QA) lesions in rats closely resemble Huntington's disease like conditions. Oxidative stress and mitochondrial dysfunction have long been implicated in the neurotoxic effects of QA acting through N-methyl-d-aspartate (NMDA) receptors. Reports suggest that inhibition of adenosine A2A receptor function elicits neuroprotective effect in QA induced neurotoxicity in rats.

Possible involvement of nitric oxide modulatory mechanism in the protective effect of retigabine against spinal nerve ligation-induced neuropathic pain.

Decreasing the hyperexcitability of neurons through opening of voltage-gated potassium (Kv7) channels has been suggested as one of the protective mechanisms in the effective management of neuropathic pain. Reactive oxygen/nitrogen species are well implicated in the pathophysiology of neuropathic pain. Further, M current generated by opening of voltage-gated potassium channels (Kv7) has been modulated by reactive oxygen/nitrogen species.

Improvement of mitochondrial function by paliperidone attenuates quinolinic acid-induced behavioural and neurochemical alterations in rats: implications in Huntington's disease.

Quinolinic acid (QA)-induced neurotoxicity involves a cascade of events such as increased calcium concentration in cytoplasm, exhaustive ATP depletion, oxidative stress, as well as selective GABAergic, dopaminergic, and cholinergic neuronal death. Clinical data hint towards the connection between signalling of dopaminergic system and efficient amelioration of chorea following a tetrabenazine administration in Huntington's disease patients. Therefore, the present study has been designed to explore the neuroprotective potential of paliperidone, an active metabolite of risperidone (a dopaminergic antagonist) against QA-induced neurotoxicity and related complications in rats.

Rosiglitazone synergizes the neuroprotective effects of valproic acid against quinolinic acid-induced neurotoxicity in rats: targeting PPARγ and HDAC pathways.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder which affects medium spiny GABAergic neurons mainly in the striatum. Oxidative damage, neuro-inflammation, apoptosis, protein aggregation, and signaling of neurotrophic factors are some of the common cellular pathways involved in HD. Quinolinic acid (QA) causes excitotoxicity by stimulating N-methyl-D-aspartate receptors via calcium overload leading to neurodegeneration.

Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Huntington's disease like symptoms in rats: behavioral, biochemical, cellular and histological evidences.

Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Besides its anti-oxidant properties, the other probable mechanisms which underpin its neuroprotective potential are still not clear. In light of emerging role of flavonoids in modulating oxidative stress and neuro-inflammation, the study has been designed to explore the possible neuroprotective effect of hesperidin and its combination with minocycline (microglial inhibitor), against quinolinic acid (QA) induced Huntington's disease (HD) like symptoms in rats.

Possible nitric oxide mechanism in the protective effect of hesperidin against pentylenetetrazole (PTZ)-induced kindling and associated cognitive dysfunction in mice.

Epilepsy is a complex neurological disorder manifested by recurrent episodes of convulsive seizures, loss of consciousness, and sensory disturbances. Pentylenetetrazole (PTZ)-induced kindling primarily represents a model of generalized epilepsy. The present study has been undertaken to evaluate the neuroprotective potential of hesperidin and its interaction with nitric oxide modulators against PTZ-induced kindling and associated cognitive dysfunction in mice.

Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington's disease like symptoms and related cognitive dysfunction in rats.

Malonic acid (MA) is a reversible inhibitor of succinate dehydrogenase (SDH) which induces mitochondrial dysfunction followed by secondary excitotoxicity and apoptosis due to generation of reactive oxygen species. Therapeutic potential of rofecoxib and statins have been well documented in several experimental models of neurodegenerative disorders, however, its exact mechanism of action is not known properly. Therefore, the present study is an attempt to investigate the effect of rofecoxib along with the statins against MA induced behavioural and biochemical alterations in rats.

Potential role of licofelone, minocycline and their combination against chronic fatigue stress induced behavioral, biochemical and mitochondrial alterations in mice.

Background: Chronic fatigue stress (CFS) is a common complaint among general population. Persistent and debilitating fatigue severely impairs daily functioning and is usually accompanied by combination of several physical and psychiatric problems. It is now well established fact that oxidative stress and neuroinflammation are involved in the pathophysiology of chronic fatigue and related disorders.

Neuroprotective potential of atorvastatin and simvastatin (HMG-CoA reductase inhibitors) against 6-hydroxydopamine (6-OHDA) induced Parkinson-like symptoms.

Neuro-inflammation and oxidative stress plays a key role in the pathophysiology of Parkinson's disease (PD). Studies demonstrated that neuro-inflammation and associated infiltration of inflammatory cells into central nervous system are inhibited by 3-hydroxy-3-methyl glutaryl co-enzyme A (HMG-CoA) reductase inhibitors. Based on these experimental evidences, the present study has been designed to evaluate the neuroprotective effect of HMG-CoA reductase inhibitors (atorvastatin and simvastatin) against 6-hydroxydopamine (6-OHDA) induced unilateral lesion model of PD.

Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.

Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats.