Neuroprotection From Soman-induced Seizures In The Rodent: Evaluation With Diffusion- And T2-weighted Magnetic Resonance Imaging

Bhagat, Yusuf A.; Obenaus, André; Hamilton, Mary G.; Mikler, John; Kendall, Edward J.

doi:10.1016/j.neuro.2005.04.006

Cited by 45 publications

(40 citation statements)

References 21 publications

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“…The damaged area depicted early in the DWMR images was found to correlate significantly with the damaged area in standard histological analysis performed on brain samples acquired 15 days post intoxication, reflecting the unique advantage of DWMRI in predicting later damage. These findings are in accordance with previous reports, demonstrating the feasibility of using DWMRI to assess brain damage in OP poisoned animals (Bhagat et al ., ; Carpentier et al ., ; Testylier et al ., ). The advantage of DWMRI when compared with the classic histology analysis is that it is a noninvasive technique, allowing short‐ and long‐term 3D follow‐up and evaluation of the same animal, with numerous optional evaluation points of follow‐up (as was done in our study).…”

Section: Discussionmentioning

confidence: 99%

Using MRI for the assessment of paraoxon‐induced brain damage and efficacy of antidotal treatment

Rosman

Eisenkraft

Krivoy

et al. 2011

J of Applied Toxicology

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Organophosphate intoxication induces neural toxicity as demonstrated in histological analysis of poisoned animals. Diffusion-weighted magnetic resonance imaging (DWMRI) enables early noninvasive characterization of biological tissues based on their water diffusion characteristics. Our objectives were to study the application of MRI for assessment of paraoxon-induced brain damage and the efficacy of antidotal treatments. Seventy-six rats were poisoned with paraoxon followed by treatment with atropine and obidoxime. The rats were then divided into five treatment groups consisting of midazolam after 1 or 30 min, scopolamine after 1 or 30 min and a no anticonvulsant treatment group. Five untreated rats served as controls. Animals underwent MRI on days 1, 8, 15, 29 and 50 post poisoning. Histological evaluation was performed on representative rat brains. Acute DWMRI effects, such as enhancement of temporal brain regions, and chronic effects such as ventricular enlargement and brain atrophy, depicted on T₂-weighted MRI, were significantly more prominent in late anticonvulsant treatment groups. There was no significant difference between the neuroprotective effects of midazolam and scopolamine as shown by DWMRI. Early MRI abnormalities were found to correlate significantly with histological analysis of samples obtained 15 days post treatment. In conclusion, our results demonstrate the feasibility of using DWMRI for depiction of early cytotoxic response to paraoxon and T₂-weighted MRI for later changes, thus enabling assessment of early/late brain damage as well as treatment efficacy in rats. The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning.

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Section: Discussionmentioning

confidence: 99%

Using MRI for the assessment of paraoxon‐induced brain damage and efficacy of antidotal treatment

Rosman

Eisenkraft

Krivoy

et al. 2011

J of Applied Toxicology

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“…influx, oxidative stress, depletion of neuronal energy status and loss of cellular homeostasis. Huperzine A may also modulate CWNA induced activation of neuroinflammatory pathways, p38 MAP kinase pathway and their targets, cerebral edema and neuronal death as well as acute BBB disruption to prevent brain injury [39,[41][42][43][44][45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

[+]-Huperzine A Protects Against Soman Toxicity in Guinea Pigs

et al. 2011

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The chemical warfare nerve agent (CWNA) soman irreversibly inhibits acetylcholinesterase (AChE) causing seizure, neuropathology and neurobehavioral deficits. Pyridostigmine bromide (PB), the currently approved pretreatment for soman, is a reversible AChE inhibitor that does not cross the blood-brain barrier (BBB) to protect against central nervous system damage. [-]-Huperzine A, a natural reversible AChE inhibitor, rapidly passes through the BBB and has numerous neuroprotective properties that are beneficial for protection against soman. However, [-]-Huperzine A is toxic at higher doses due to potent AChE inhibition which limits the utilization of its neuroprotective properties. [+]-Huperzine A, a synthetic stereoisomer of [-]-Huperzine A and a weak inhibitor of AChE, is non-toxic. In this study, we evaluated the efficacy of [+]-Huperzine A for protection against soman toxicity in guinea pigs. Pretreatments with [+]-Huperzine A, i.m., significantly increased the survival rate in a dose-dependent manner against 1.2× LD(50) soman exposures. Behavioral signs of soman toxicity were significantly reduced in 20 and 40 mg/kg [+]-Huperzine A treated animals at 4 and 24 h compared to vehicle and PB controls. Electroencephalogram (EEG) power spectral analysis showed that [+]-Huperzine A significantly reduces soman-induced seizure compared to PB. [+]-Huperzine A (40 mg/kg) preserved higher blood and brain AChE activity compared to PB in soman exposed animals. These data suggest that [+]-Huperzine A protects against soman toxicity stronger than PB and warrant further development as a potent medical countermeasure against CWNA poisoning.

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“…When clonazepam was combined with a muscimol agonist chrolmethizol, the overall neuroprotective effect was enhanced (MacGregor et al, 1997). Likewise, diazepam treatment immediately after soman induced seizures considerably prevented pathophysiological alterations in the hippocampus as well as the piriform cortex (Bhagat et al, 2005).…”

Section: Conventional Antiepileptic Drugsmentioning

confidence: 99%

Progress in neuroprotective strategies for preventing epilepsy

Acharya

Hattiangady

Shetty

2008

Progress in Neurobiology

158

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Neuroprotection is increasingly considered as a promising therapy for preventing and treating temporal lobe epilepsy (TLE). The development of chronic TLE, also termed as epileptogenesis, is a dynamic process. An initial precipitating injury (IPI) such as the status epilepticus (SE) leads to neurodegeneration, abnormal reorganization of the brain circuitry and a significant loss of functional inhibition. All of these changes likely contribute to the development of chronic epilepsy, characterized by spontaneous recurrent motor seizures (SRMS) and learning and memory deficits. The purpose of this review is to discuss the current state of knowledge pertaining to neuroprotection in epileptic conditions, and to highlight the efficacy of distinct neuroprotective strategies for preventing or treating chronic TLE. Although the administration of certain conventional and new generation antiepileptic drugs is effective for primary neuroprotection such as reduced neurodegeneration after acute seizures or the SE, their competence for preventing the development of chronic epilepsy after an IPI is either unknown or not promising. On the other hand, alternative strategies such as the ketogenic diet therapy, administration of distinct neurotrophic factors, hormones or antioxidants seem useful for preventing and treating chronic TLE. However, long term studies on the efficacy of these approaches introduced at different time-points after the SE or an IPI are lacking. Additionally, grafting of fetal hippocampal cells at early time-points after an IPI holds considerable promise for preventing TLE, though issues regarding availability of donor cells, ethical concerns, timing of grafting after SE, and durability of graft-mediated seizure suppression need to be resolved for further advances with this approach. Overall, from the studies performed so far, there is consensus that neuroprotective strategies need to be employed as quickly as possible after the onset of the SE or an IPI for considerable beneficial effects. Nevertheless, ideal strategies that are capable of facilitating repair and functional recovery of the brain after an IPI and preventing the evolution of IPI into chronic epilepsy are still hard to pin down.

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Neuroprotection From Soman-induced Seizures In The Rodent: Evaluation With Diffusion- And T2-weighted Magnetic Resonance Imaging

Cited by 45 publications

References 21 publications

Using MRI for the assessment of paraoxon‐induced brain damage and efficacy of antidotal treatment

Using MRI for the assessment of paraoxon‐induced brain damage and efficacy of antidotal treatment

[+]-Huperzine A Protects Against Soman Toxicity in Guinea Pigs

Progress in neuroprotective strategies for preventing epilepsy

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