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Background: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited that neuroinflammation plays a key role in the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing of this hypothesis requires preclinical models that recapitulate relevant phenotypic outcomes. Here, we describe a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) that exhibits persistent neuroinflammation and cognitive impairment., Methods: Neuroinflammation, neurodegeneration, and cognitive function were compared in adult male Sprague Dawley rats injected with an acutely toxic dose of DFP vs. vehicle controls at multiple time points up to 36 days post-exposure. Neuroinflammation was quantified using immunohistochemical biomarkers of microglia (ionized calcium-binding adapter molecule 1, IBA1) and activated astrocytes (glial fibrillary acidic protein, GFAP) and positron emission tomography (PET) imaging of [ 11 C]-(R)-PK11195, a ligand for the 18-kDa mitochondrial membrane translocator protein (TSPO). FluoroJade-B staining was used to assess neurodegeneration; Pavlovian conditioning, to assess cognitive function., Results: Animals exhibited moderate-to-severe seizures within minutes of DFP injection that continued for up to 6 h post-injection. As indicated by IBA1 and GFAP immunoreactivity and by PET imaging of TSPO, acute DFP intoxication triggered neuroinflammation in the hippocampus and cortex during the first 3 days that peaked at 7 days and persisted to 21 days post-exposure in most animals. Neurodegeneration was detected in multiple brain regions from 1 to 14 days post-exposure. All DFP-intoxicated animals exhibited significant deficits in contextual fear conditioning at 9 and 20 days post-exposure compared to vehicle controls. Whole-brain TSPO labeling positively correlated with seizure severity score, but did not correlate with performance in the contextual fear-conditioning task., Conclusions: We describe a preclinical model in which acute DFP intoxication causes seizures, persistent neuroinflammation, neurodegeneration, and memory impairment. The extent of the neuroinflammatory response is influenced by seizure severity. However, the observation that a subset of animals with moderate seizures and minimal TSPO labeling exhibited cognitive deficits comparable to those of animals with severe seizures and significant TSPO labeling suggests that DFP may impair learning and memory circuitry via mechanisms independent of seizures or neuroinflammation.

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABAAR) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABAAR positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15mg/kg, ip). Administration of a high dose of diazepam (5mg/kg, ip) immediately following the second clonic seizure (approximately 20min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABAAR antagonists. The sEH inhibitor TUPS (1mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5mg/kg, ip) and TUPS (1mg/kg, ip, starting 1h after diazepam and repeated every 24h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Organophosphorus (OP) nerve agents and pesticides inhibit acetylcholinesterase (AChE), and this is thought to be a primary mechanism mediating the neurotoxicity of these compounds. However, a number of observations suggest that mechanisms other than or in addition to AChE inhibition contribute to OP neurotoxicity. There is significant experimental evidence that acute OP intoxication elicits a robust inflammatory response, and emerging evidence suggests that chronic repeated low-level OP exposure also upregulates inflammatory mediators. A critical question that is just beginning to be addressed experimentally is the pathophysiologic relevance of inflammation in either acute or chronic OP intoxication. The goal of this article is to provide a brief review of the current status of our knowledge linking inflammation to OP intoxication, and to discuss the implications of these findings in the context of therapeutic and diagnostic approaches to OP neurotoxicity., (Published by Elsevier B.V.)

Tetramethylenedisulfotetramine (tetramine; TETS) is a potent convulsant poison that is considered to be a chemical threat agent. To provide a basis for the investigation of antidotes for TETS-induced seizures, we characterized the convulsant activity of TETS in mice and rats when administered by the intraperitoneal, intravenous, oral, and intraventricular routes as a single acute dose and with repeated sublethal doses. In mice, parenteral and oral TETS caused immobility, myoclonic body jerks, clonic seizures of the forelimbs and/or hindlimbs, tonic seizures, and death. The CD₅₀ values for clonic and tonic seizures after oral administration were 0.11 and 0.22 mg/kg, respectively. Intraventricular administration of TETS (5-100 μg) in rats also caused clonic-tonic seizures and death. In mice, repeated sublethal doses of TETS at intervals of 2, 24, and 48 h failed to result in the development of persistent enhanced seizure responsivity ("kindling") as was observed with repeated pentylenetetrazol treatment. In mice, sublethal doses of TETS that produced clonic seizures did not cause observable structural brain damage as assessed with routine histology and Fluoro-Jade B staining 7 days after treatment. However, 1 to 3 days after a single convulsant dose of TETS the expression of glial fibrillary acidic protein, an astrocyte marker, and ionized calcium binding adaptor molecule 1, a microglia marker, were markedly increased in cortex and hippocampus. Although TETS doses that are compatible with survival are not associated with overt evidence of cellular injury or neurodegeneration, there is transient reactive astrocytosis and microglial activation, indicating that brain inflammatory responses are provoked.

The emerald jewel wasp, Ampulex compressa, exploits the American cockroach, Periplaneta americana, as a host for its progeny. The wasp subdues the host by stinging directly into the brain and subesophageal ganglion, inducing long-term hypokinesia. The hypokinesic host lacks normal escape behavior and motivation to walk, making it easy for subjugation by the wasp. The mechanism underlying hypokinesia induction is not known, but depletion of monoamines induces behavior resembling venom-induced hypokinesia. To test whether amine depletion occurs in stung animals, we used high-performance liquid chromatography with electrochemical detection (HPLC-ED) to measure quantitatively amine levels in the central nervous system. Our data show clearly that levels of dopamine, serotonin, octopamine and tyramine remain unchanged in stung animals, whereas animals treated with reserpine exhibited marked depletion of all amines sampled. Furthermore, stung animals treated with reserpine show depletion of amines, demonstrating that envenomation also does not interfere with amine release. These results show that hypokinesia induced by Ampulex venom does not result from amine depletion or inability to release monoamines in the central nervous system., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The principal and contributing causes of blindness for all pensions granted by the Department of Social Security on account of blindness in Australia during the year ending 30 June 1984 have been coded according to the International Classification of Diseases, 1975 (ICD9). The results are presented in tables which show the major diagnosis for symmetrical and asymmetrical cases according to frequency and age, and the combination of major and contributing diagnosis according to age, sex and prevalence per 100 persons.

The information available on the prevalence of blindness in Australia is examined in an attempt to estimate the number of blind people in New South Wales. Records of the causes of blindness made by the authors at the Royal Blind Society's Low Vision Clinic are then examined to estimate their relative significance. There are at least seven thousand people blind, out of a total population of 5,145,900. Macula pathology contributes 37.2% and 81.5% of those affected are over 60 years old. Diabetes is responsible for approximately 10%. Genetically determined disease causes 25% between ages 16 and 60 years. If blindness is to be prevented, a more detailed analysis of causes will be needed. This could be obtained by examination and coding of the records for Disability (Blind) Pensions at the Department of Social Security. Blindness in Aboriginals is not discussed.

Thirteen anorexia nervosa patients and 13 control subjects were examined for cataract and xerophthalmia. Although 11 patients had Vitamin A intakes below recommended daily levels for significant periods of time, there was no evidence to suggest that they had an increased incidence of pathological changes in conjunctiva or lens.

The aim of the paper is not to present new facts or theories but to remind Ophthalmologists that visual rehabilitation is part of continuing eye care. Case histories will be presented to show that it has a place in interim management of acute visual loss, as well as paralleling the care of more chronic problems. The services available and the ways in which they can be co-ordinated are discussed.