Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity

2014 ◽  
Vol 92 (11) ◽  
pp. 893-911 ◽  
Author(s):  
Shamsherjit Kaur ◽  
Satinderpal Singh ◽  
Karan Singh Chahal ◽  
Atish Prakash
Keyword(s):  
Brain Damage ◽  
Calcium Influx ◽  
Neuronal Damage ◽  
Cholinergic Neurons ◽  
Sensory Deficits ◽  
Neuroprotective Strategies ◽  
Late Stages ◽  
The Brain ◽  
Beneficial Approach ◽  
Cholinergic Projection

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

scholarly journals Chronic Dexamethasone Pretreatment Aggravates Ischemic Neuronal Necrosis

1986 ◽  
Vol 6 (4) ◽  
pp. 395-404 ◽  
Author(s):  
Tohru Koide ◽  
Tadeusz W. Wieloch ◽  
Bo K. Siesjö
Keyword(s):  
Brain Damage ◽  
Glucocorticoid Receptors ◽  
Neuronal Damage ◽  
Energy Charge ◽  
Cyclooxygenase Inhibitors ◽  
Brain Areas ◽  
Neuronal Necrosis ◽  
Brain Glucose ◽  
Glucose Levels ◽  
The Brain

This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.

scholarly journals Hippocampal Damage following Repeated Brief Hypotensive Episodes in the Rat

1991 ◽  
Vol 11 (6) ◽  
pp. 974-978 ◽  
Author(s):  
Yoichi Yamauchi ◽  
Hiroyuki Kato ◽  
Kyuya Kogure
Keyword(s):  
Brain Damage ◽  
Neuronal Damage ◽  
Neuronal Loss ◽  
Hippocampal Damage ◽  
Shed Blood ◽  
Arterial Blood ◽  
Hippocampal Ca1 ◽  
Severe Hypotension ◽  
The Brain ◽  
Hippocampal Ca1 Subfield

We examined the brain damage following repeated hypotensive episodes in the rat. Severe hypotension was induced by withdrawal of arterial blood. The MABP was maintained at about 25 mm Hg with isoelectric EEG and the shed blood was retransfused. After 1 week of recovery, histopathological changes were examined. No brain damage was observed after 1 min of isoelectric EEG. Mild neuronal damage to the hippocampal CA1 subfield was seen in some animals after two episodes of 1-min isoelectric EEG at a 1-h interval. Significant and consistent neuronal loss in the hippocampal CA1 subfield was observed after three episodes of 1-min isoelectric EEG. Scattered neuronal damage in the thalamus was additionally seen in some animals. The present study indicates that repeated brief hypotensive episodes produce brain damage depending on the number of episodes, even though no brain damage results when induced as a single insult. This animal model may reproduce hemodynamic transient ischemic attacks in humans.

Rehabilitation of Attention

2003 ◽  
Vol 14 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Ian H. Robertson
Keyword(s):  
Brain Damage ◽  
Dependent Plasticity ◽  
Attention Systems ◽  
The Brain

Abstract: In this paper, evidence is reviewed for separable attention systems in the brain, and it is argued a) that attention may have a privileged role in mediating experience dependent plasticity in the brain and b) that at least some types of attention may be capable of rehabilitation following brain damage.

Current Strategies and Novel Drug Approaches for Alzheimer Disease

2020 ◽  
Vol 19 (9) ◽  
pp. 676-690 ◽  
Author(s):  
Roma Ghai ◽  
Kandasamy Nagarajan ◽  
Meenakshi Arora ◽  
Parul Grover ◽  
Nazakat Ali ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons ◽  
Amyloid Plaque ◽  
Neural Pathways ◽  
Current Trends ◽  
Personality Changes ◽  
Traditional Therapies ◽  
Novel Drug ◽  
The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Aetiologies and anatomy of confabulation

2017 ◽  
Author(s):  
Armin Schnider
Keyword(s):  
Brain Damage ◽  
Limbic Encephalitis ◽  
Artery Aneurysm ◽  
Anterior Communicating Artery ◽  
Brain Areas ◽  
Anatomical Basis ◽  
Korsakoff Syndrome ◽  
Hypoxic Brain ◽  
Degenerative Dementia ◽  
The Brain

What diseases cause confabulations and which are the brain areas whose damage is responsible? This chapter reviews the causes, both historic and present, of confabulations and deduces the anatomo-clinical relationships for the four forms of confabulation in the following disorders: alcoholic Korsakoff syndrome, traumatic brain injury, rupture of an anterior communicating artery aneurysm, posterior circulation stroke, herpes and limbic encephalitis, hypoxic brain damage, degenerative dementia, tumours, schizophrenia, and syphilis. Overall, clinically relevant confabulation is rare. Some aetiologies have become more important over time, others have virtually disappeared. While confabulations seem to be more frequent after anterior brain damage, only one form has a distinct anatomical basis.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

scholarly journals Zingiber officinaleMitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Brain Infarct ◽  
Ginger Rhizome ◽  
The Brain

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist

1991 ◽  
Vol 74 (6) ◽  
pp. 944-950 ◽  
Author(s):  
Min-Hsiung Chen ◽  
Ross Bullock ◽  
David I. Graham ◽  
Jimmy D. Miller ◽  
James McCulloch
Keyword(s):  
Brain Damage ◽  
Subdural Hematoma ◽  
Neuronal Damage ◽  
Nmda Receptor Antagonist ◽  
Acute Subdural Hematoma ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Content Type ◽  
Irreversible Brain Damage ◽  
Slow Injection

✓ The ability of a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (D-CPP-ene) to reduce irreversible brain damage has been examined in a rodent model of acute subdural hematoma. Acute subdural hematoma was produced by the slow injection of 400 µl homologous blood into the subdural space overlying the parietal cortex in halothane-anesthetized rats. Brain damage was assessed histologically in sections at multiple coronal planes in animals sacrificed 4 hours after induction of the subdural hematoma. Pretreatment with D-CPP-ene (15 mg/kg) significantly reduced the volume of ischemic brain damage produced by the subdural hematoma from 62 ± 8 cu mm (mean ± standard error of the mean) in vehicle-treated control rats to 29 ± 7 cu mm in drug-treated animals. These data demonstrate the anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage in which intracranial pressure is elevated, and suggest that excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage which is observed in patients who die after acute subdural hematoma.

scholarly journals STUDIES ON THE PATHOGENESIS OF KERNICTERUS

1953 ◽  
Vol 98 (5) ◽  
pp. 509-520 ◽  
Author(s):  
F. Stephen Vogel
Keyword(s):  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Nerve Cells ◽  
Brain Barrier ◽  
Maximum Absorption ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Absorption Of Light ◽  
The Brain

Kernicteric pigment was extracted by means of chloroform from the brains of 3 infants. Solutions of it gave a positive diazo reaction, and, as determined electrophotometrically, gave maximum absorption of light having a wavelength of 425 mµ, being identical in these properties with chloroform solutions of crystalline mesobilirubin. Experimental kernicterus was regularly induced by injecting crystalline mesobilirubin intracerebrally in newborn kittens, the pigment staining the cerebral tissues a bright canary-yellow and being deposited abundantly in the nerve cells, as microscopic examinations showed, although these latter were otherwise intact. Bilirubin, likewise injected intracerebrally in newborn kittens, had no such effects. The possibility is discussed that the blood-brain barrier is altered in some infants with hyperbilirubinemia in such a way that bilirubin crosses it and is then reduced within the brain to mesobilirubin thus giving rise to the cerebral pigmentation of kernicterus. The fact that the pigment itself does not seem to damage the neurons, as the present studies show, makes it necessary to seek some other cause for the neuronal damage that is sometimes seen, in association with the pigmentation, in the naturally occurring disease.

Race and Rorschach Signs of Brain Damage in Cerebral Thrombosis

1966 ◽  
Vol 22 (2) ◽  
pp. 655-662 ◽  
Author(s):  
Ray B. Evans ◽  
Jessie Marmorston
Keyword(s):  
Myocardial Infarction ◽  
Brain Damage ◽  
Cerebral Thrombosis ◽  
The Brain ◽  
Item Scale

In an attempt to identify Rorschach signs which would differentiate the brain-damaged regardless of race, a study was made of 225 Caucasian and 127 Negro patients between 40 and 80 yr. of age. There was known brain damage (cerebral thrombosis) in 204 patients, and no known brain damage in 148 patients (myocardial infarction). Each of 31 Rorschach signs of cerebral impairment was studied to determine its power in discriminating Caucasian damaged from nondamaged and Negro damaged from nondamaged patients. A combination of 13 signs was thereby selected in which race did not appear to be a significant factor. The 13-item scale differentiated brain-damaged from nondamaged Caucasian, Negro, and combined Caucasian-Negro groups, all at levels below .001. The 13-item scale correctly classified 71% of the patients, compared with 73% when all 31 signs were used.

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